Madduri, Deepu

PURPOSE CARTITUDE-1, a phase Ib/II study evaluating the safety and efficacy of ciltacabtagene autoleucel (cilta-cel) in heavily pretreated patients with relapsed/refractory multiple myeloma, yielded early, deep, and durable responses at 12 months. Here, we present updated results 2 years after last patient in (median follow-up [MFU] approximately 28 months), including analyses of high-risk patient subgroups. METHODS Eligible patients had relapsed/refractory multiple myeloma, had received ≥ 3 prior lines of therapy or were double refractory to a proteasome inhibitor and immunomodulatory drug and had received prior proteasome inhibitor, immunomodulatory drug, and anti-CD38 therapy. Patients received a single cilta-cel infusion 5-7 days after lymphodepletion. Responses were assessed by an independent review committee. RESULTS At a MFU of 27.7 months (N = 97), the overall response rate was 97.9% (95% CI, 92.7 to 99.7); 82.5% (95% CI, 73.4 to 89.4) of patients achieved a stringent complete response. Median duration of response was not estimable. Median progression-free survival (PFS) and overall survival (OS) were not reached; 27-month PFS and OS rates were 54.9% (95% CI, 44.0 to 64.6) and 70.4% (95% CI, 60.1 to 78.6), respectively. Overall response rates were high across all subgroups (95.1%-100%). Duration of response, PFS, and/or OS were shorter in patients with high-risk cytogenetics, International Staging System stage III, high tumor burden, or plasmacytomas. The safety profile was manageable with no new cilta-cel–related cytokine release syndrome and one new case of parkinsonism (day 914 after cilta-cel) since the last report. CONCLUSION At approximately 28 months MFU, patients treated with cilta-cel maintained deep and durable responses, observed in both standard and high-risk subgroups. The risk/benefit profile of cilta-cel remained favorable with longer follow-up.

Abstract Introduction: Ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor T (CAR-T) cell therapy with 2 B-cell maturation antigen (BCMA) targeting single-domain antibodies, demonstrated early, deep, and durable responses in the phase 1b/2 CARTITUDE-1 study in patients (pts) with relapsed/refractory multiple myeloma (RRMM) who had been heavily pretreated (Berdeja, Lancet, 2021). After a median follow-up of 12.4 months, the overall response rate (ORR; as assessed by independent review committee) was 97%, with 67% of pts achieving stringent complete response (sCR). The 12-month progression-free survival (PFS) and overall survival (OS) rates were 77% and 89%, respectively. Here, we report updated results from CARTITUDE-1 with longer duration of follow-up (median 18 months). Methods: Eligible pts had MM and received ≥3 prior therapies or were refractory to a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), and had received a PI, IMiD, and an anti-CD38 antibody. After apheresis, bridging therapy was permitted. Pts received a single cilta-cel infusion (target dose 0.75×10 6 CAR+ viable T cells/kg; range 0.5-1.0×10 6) 5-7 days (d) after lymphodepletion (300 mg/m 2 cyclophosphamide, 30 mg/m 2 fludarabine daily for 3 d). Primary objectives were to characterize cilta-cel safety, confirm the recommended phase 2 dose (phase 1b), and evaluate cilta-cel efficacy (phase 2). Response was assessed per IMWG criteria by an independent review committee and minimal residual disease (MRD) negativity at 10 -5 by next-generation sequencing. In this combined phase 1b and phase 2 analysis, cytokine release syndrome (CRS; per Lee et al Blood 2014 grading criteria) and neurotoxicity (by CTCAE v5.0) were mapped to the ASTCT criteria for CRS and immune effector cell-associated neurotoxicity (ICANS), respectively. Results: As of Feb 11, 2021, 97 pts (58.8% male; median age 61.0 years [range 43-78]) received cilta-cel. Pts had received a median of 6 (range 3-18) prior lines of therapy; 83.5% were penta-drug exposed, 87.6% were triple-class refractory, 42.3% were penta-drug refractory, and 99.0% were refractory to last line of therapy. ORR was 97.9% (95% CI: 92.7-99.7); 80.4% of pts achieved sCR, and 94.8% achieved very good partial response or better (Figure). The median time to first response was 1 month (range 0.9-10.7), median time to best response was 2.6 months (range 0.9-15.2), and median time to complete response or better was 2.6 months (range 0.9-15.2). The median duration of response was 21.8 months (95% CI: 21.8-not estimable). Of 61 pts evaluable for MRD, 91.8% were MRD negative at the 10 -5 threshold; MRD 10 -5 negativity was sustained for ≥6 months in 44.3% (27/61) of pts and ≥12 months in 18% (11/61) of pts. The 18-month PFS and OS rates were 66.0% (95% CI: 54.9-75.0) and 80.9% (95% CI: 71.4-87.6), respectively. 18-month PFS rates in pts who achieved sustained MRD for ≥6 months and ≥12 months were 96.3% (95% CI: 76.5-99.5) and 100%, respectively. The most common grade 3/4 hematologic AEs in ≥25% of pts were neutropenia (94.8%), anemia (68.0%), leukopenia (60.8%), thrombocytopenia (59.8%), and lymphopenia (49.5%). There were no fatalities related to cytopenias, and no new safety signals with longer follow-up. CRS occurred in 94.8% of pts (mostly grade 1/2); median time to onset was 7 d (range 1-12), and CRS resolved within 14 d in 98.9% of pts. There was no new CAR T-cell neurotoxicity since the previous report. Post cilta-cel infusion, 21 deaths occurred during the study: 0 within first 30 d, 2 within 100 d, and 19 more than 100 d post infusion. Ten deaths were due to disease progression, 6 were treatment-related (as assessed by the investigator), and 5 were due to AEs unrelated to treatment. One patient was retreated with cilta-cel (for progressive disease) and had stable disease (per computerized algorithm) post-retreatment with no incidence of CAR T-cell neurotoxicity. Conclusions: At a longer median follow-up of 18 months, a single cilta-cel infusion led to early, deep, and durable responses in heavily pre-treated pts with MM. Follow-up is ongoing and updated data will be presented. Cilta-cel demonstrated a manageable safety profile with no new safety signals observed with longer follow-up. Further investigations of cilta-cel are ongoing in earlier lines of therapy (CARTITUDE-2 [NCT04133636], CARTITUDE-4 [NCT04181827], and CARTITUDE-5 [NCT04923893]) and in outpatient settings. Figure 1 Figure 1. Disclosures Martin: GlaxoSmithKline: Consultancy; Janssen: Research Funding; Sanofi: Research Funding; Amgen: Research Funding. Usmani: Takeda: Consultancy, Research Funding, Speakers Bureau; SkylineDX: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Janssen Oncology: Consultancy, Research Funding; Bristol-Myers Squibb: Research Funding; EdoPharma: Consultancy; Array BioPharma: Consultancy, Research Funding; Celgene/BMS: Consultancy, Research Funding, Speakers Bureau; GSK: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; Amgen: Consultancy, Research Funding, Speakers Bureau; Abbvie: Consultancy. Berdeja: Lilly, Novartis: Research Funding; Poseida, Sanofi, Teva: Research Funding; GSK, Ichnos Sciences, Incyte: Research Funding; Bluebird bio, BMS, Celgene, CRISPR Therapeutics, Janssen, Kite Pharma, Legend Biotech, SecuraBio, Takeda: Consultancy; Celularity, CRISPR Therapeutics: Research Funding; Abbvie, Acetylon, Amgen: Research Funding; EMD Sorono, Genentech: Research Funding. Jakubowiak: Amgen: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Gracell: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Cohen: Novartis: Research Funding; BMS/Celgene: Consultancy; Takeda: Consultancy; Genentech/Roche: Consultancy; Oncopeptides: Consultancy; AstraZeneca: Consultancy; Janssen: Consultancy; GlaxoSmithKline: Consultancy, Research Funding. Hari: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau; Karyopharm: Consultancy; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millenium: Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau; Adaptive Biotech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau; Celgene-BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau. Avigan: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Kite Pharma: Consultancy, Research Funding; Juno: Membership on an entity's Board of Directors or advisory committees; Partner Tx: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Aviv MedTech Ltd: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Legend Biotech: Membership on an entity's Board of Directors or advisory committees; Chugai: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; Parexcel: Consultancy; Takeda: Consultancy; Sanofi: Consultancy. Deol: Kite, a Gilead Company: Consultancy. Lesokhin: bristol myers squibb: Research Funding; Iteos: Consultancy; pfizer: Consultancy, Research Funding; Behringer Ingelheim: Honoraria; Trillium Therapeutics: Consultancy; Serametrix, Inc: Patents & Royalties; Genetech: Research Funding; Janssen: Honoraria, Research Funding. Munshi: Adaptive Biotechnology: Consultancy; Karyopharm: Consultancy; Oncopep: Consultancy, Current equity holder in publicly-traded company, Other: scientific founder, Patents & Royalties; Legend: Consultancy; Novartis: Consultancy; Abbvie: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Takeda: Consultancy; Amgen: Consultancy; Pfizer: Consultancy; Bristol-Myers Squibb: Consultancy. O'Donnell: Onocopeptide: Consultancy; Karyopharm: Consultancy; Janssen: Consultancy; Bristol Myer Squibb: Consultancy; Adaptive: Consultancy; Takeda: Consultancy. Stewart: Oncopeptides: Honoraria; Janssen: Honoraria; GSK: Honoraria; BMS: Honoraria; Amgen: Honoraria; Skyline diagnostics: Consultancy; Genomcs England: Membership on an entity's Board of Directors or advisory committees; Tempus Inc.: Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees; PikSci Inc.: Current holder of individual stocks in a privately-held company, Patents & Royalties; Sanofi Aventis: Honoraria. Schecter: Janssen: Current Employment, Current holder of stock options in a privately-held company. Goldberg: Janssen: Current Employment, Current holder of individual stocks in a privately-held company. Jackson: Janssen: Current Employment; Memorial Sloan Kettering Cancer Center: Consultancy. Yeh: Janssen: Current Employment. Banerjee: Janssen: Current Employment, Current holder of individual stocks in a privately-held company. Allred: Janssen: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Zudaire: Janssen: Current Employment. Deraedt: Janssen: Current Employment. Olyslager: Janssen: Current Employment. Pacaud: Legend Biotech: Current Employment. Lin: Juno: Consultancy; Bluebird Bio: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy; Takeda: Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Vineti: Consultancy; Gamida Cell: Consultancy; Sorrento: Consultancy; Legend: Consultancy; Merck: Research Funding; Janssen: Consultancy, Research Funding. Jagannath: Legend Biotech: Consultancy; Karyopharm Therapeutics: Consultancy; Janssen Pharmaceuticals: Consultancy; Bristol Myers Squibb: Consultancy; Sanofi: Consultancy; Takeda: Consultancy. OffLabel Disclosure: At the time of abstract submission, cilta-cel is being investigated for the treatment of multiple myeloma but is not yet approved.

Abstract Introduction: Cytokine release syndrome (CRS) is a common toxicity associated with chimeric antigen receptor (CAR) T-cell therapies. Corticosteroids and steroid-sparing therapies such as tocilizumab, an interleukin-6 receptor antagonist, and anakinra, an interleukin-1 receptor antagonist, have been used to reduce the incidence and severity of these toxicities. Preclinical and clinical case studies of anakinra, administered subcutaneously or intravenously at various doses, have shown promising results in the management of CRS and systemic inflammatory responses resembling hemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS). In CARTITUDE-1, CRS occurred in 95% of heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM) receiving ciltacabtagene autoleucel (cilta-cel), a CAR T-cell therapy with 2 B-cell maturation antigen-targeting single-domain antibodies (Berdeja et al. Lancet 2021). Per protocol, tocilizumab was required to manage CRS with option to give steroids and/or anakinra per investigator discretion. Here, we report the institutional experiences of anakinra use in the management of CRS in patients who have received cilta-cel as part of the CARTITUDE-1 study. Methods: Eligible patients had MM and received ≥3 prior therapies or were refractory to a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), and had received a PI, IMiD, and anti-CD38 antibody (Berdeja et al. Lancet 2021). After apheresis, bridging therapy was permitted. Patients received a single cilta-cel infusion (target dose: 0.75×10 6 CAR+ viable T cells/kg; range 0.5-1.0×10 6) 5-7 days after lymphodepletion (300 mg/m 2 cyclophosphamide, 30 mg/m 2 fludarabine daily for 3 days). Lee et al (Blood 2014) grading criteria for CRS were mapped to the ASTCT criteria for CRS. Post-hoc analysis of data revealed use of anakinra at some sites in patients who failed to respond to the initial management of CRS with tocilizumab +/- dexamethasone or in clinical settings where rise of ferritin and/or liver function tests were indicative for continued HLH/MAS-like manifestations (Kennedy et al. ASH 2020). Results: Of 97 patients in CARTITUDE-1, CRS occurred in 92 (95%) patients; 4% were grade 3/4. The median time to onset was 7 days (range 1-12) and median duration was 4 days (range 1-14). Supportive measures to treat CRS were administered to 91% of patients, most commonly tocilizumab (69%; 4 patients received ≥3 doses), corticosteroids (22%), and anakinra (18 patients, 19%). CRS resolved in 99% of patients. Anakinra was administered after initial tocilizumab and within the first 48 hours (range 0-6 days) of CRS onset for the majority of patients as part of effective management of CRS. Anakinra was administered at a dose of 100-200 mg every 8-12 hours over a median of 2.5 days (range 1-15 days). CRS uniformly resolved following anakinra use in CARTITUDE-1, apart from one patient who died from sepsis (grade 5 outcome) due to HLH/MAS considered related to treatment (Table). Conclusions: CRS events in cilta-cel-treated patients in CARTITUDE-1 were common, generally low-grade, and successfully managed with standard tocilizumab +/- dexamethasone. The use of anakinra should be considered in patients with persistent CRS/inflammatory symptoms despite tocilizumab use, and in particular in patients with HLH/MAS-like symptoms/phenotype occurring following CRS or in the absence of prior CRS. Figure 1 Figure 1. Disclosures Wong: Amgen: Consultancy; Genentech: Research Funding; Fortis: Research Funding; Janssen: Research Funding; GloxoSmithKlein: Research Funding; Dren Biosciences: Consultancy; Caelum: Research Funding; BMS: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees. Richard: Karyopharm, Janssen: Honoraria. Lin: Juno: Consultancy; Legend: Consultancy; Merck: Research Funding; Bluebird Bio: Consultancy, Research Funding; Sorrento: Consultancy; Janssen: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Novartis: Consultancy; Celgene: Consultancy, Research Funding; Takeda: Research Funding; Gamida Cell: Consultancy; Vineti: Consultancy. Madduri: Janssen: Current Employment. Jackson: Janssen: Current Employment; Memorial Sloan Kettering Cancer Center: Consultancy. Zudaire: Janssen: Current Employment. Romanov: Janssen: Current Employment. Trigg: Janssen: Current Employment. Vogel: Janssen Global Services, LLC: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company, Divested equity in a private or publicly-traded company in the past 24 months. Garrett: Legend Biotech USA: Current Employment. Nesheiwat: Legend Biotech USA: Current Employment. Martin: Oncopeptides: Consultancy; Sanofi: Research Funding; Janssen: Research Funding; GlaxoSmithKline: Consultancy; Amgen: Research Funding. Jagannath: Bristol Myers Squibb: Consultancy; Legend Biotech: Consultancy; Karyopharm Therapeutics: Consultancy; Janssen Pharmaceuticals: Consultancy; Takeda: Consultancy; Sanofi: Consultancy. OffLabel Disclosure: At the time of abstract submission, cilta-cel is being investigated for the treatment of multiple myeloma but is not yet approved

Abstract Introduction: Ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor T-cell (CAR-T) therapy with 2 B-cell maturation antigen (BCMA)-targeting single-domain antibodies, is being evaluated in patients (pts) with relapsed/refractory multiple myeloma (RRMM). In the phase 1b/2 CARTITUDE-1 (NCT03548207) study, a single dose of cilta-cel led to early, deep, and durable responses in heavily pretreated pts with MM, with a manageable safety profile (Berdeja, Lancet, 2021). At median 18 months of follow-up, the overall response rate (ORR) was 98%, with 80% of pts achieving stringent complete response. Median duration of response (DOR) was 21.8 months (95% CI, 21.8-not estimable); 18-month progression-free survival (PFS) and overall survival (OS) rates were 66% and 81%, respectively. Here, we report the efficacy and safety of cilta-cel in various subgroups of pts in CARTITUDE-1. Methods: Eligible pts had MM and received ≥3 prior lines of therapy (LOT) or were double refractory to a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), and had received a PI, IMiD, and anti-CD38 antibody. After apheresis, bridging therapy was permitted. Pts received a single cilta-cel infusion (target dose: 0.75×10 6 CAR+ viable T cells/kg; range 0.5-1.0×10 6) 5-7 days after lymphodepletion (300 mg/m 2 cyclophosphamide, 30 mg/m 2 fludarabine daily for 3 days). Primary objectives were to characterize cilta-cel safety, confirm the recommended phase 2 dose (phase 1b), and evaluate efficacy (phase 2). In this combined phase 1b and phase 2 analysis, cytokine release syndrome (CRS) graded by Lee et al (Blood 2014) criteria and neurotoxicity by CTCAE v5.0 were mapped to the ASTCT criteria for CRS and immune effector cell-associated neurotoxicity (ICANS), respectively. Efficacy and safety were evaluated in the following subgroups: ≥65 years of age, Black/African American, 3 prior LOT, ≥4 prior LOT, triple-class refractory, penta-drug refractory, standard- and high-risk cytogenetics, International Staging System stage III, bone marrow plasma cells at baseline (≤30%, >30 to <60%, and ≥60%), BCMA tumor expression at baseline (<80%, ≥80%), and presence of soft tissue plasmacytomas (bone-based and extramedullary). Results: As of February 11, 2021, 97 pts in the overall population received cilta-cel; 58.8% were male, median age was 61 years (range 43-78), and median time from diagnosis to enrollment was 5.9 years (range 1.6-18.2). ORR across all evaluated subgroups was comparable to the overall population, and was consistently high (range 95.1-100%) including in those with high-risk cytogenetics, ISS stage III MM, baseline bone marrow cells ≥60%, and baseline plasmacytomas (Table). Median DOR for most subgroups, including high-risk cytogenetics, was consistent with the overall population or not reached but was shorter in pts with ISS Stage III MM and baseline plasmacytomas (Table). Across all subgroups, 80%-100% of MRD-evaluable pts achieved MRD negativity (10 -5 threshold). 18-month PFS and OS rates were consistent with the overall population in most subgroups, including high-risk cytogenetics, and lower in ISS stage III and baseline plasmacytomas (Table). Incidence of CRS, ICANS, and other CAR T-cell neurotoxicities (events not reported as ICANS [ie, onset after a period of recovery from CRS and ICANS]) in various subgroups was consistent with the overall population, with no new safety signals. Conclusions: At median follow-up of 18 months, a single infusion of cilta-cel yielded deep, durable responses in all evaluated subgroups in CARTITUDE-1. An ORR of 95%-100% was observed in pts across all subgroups, including those with high-risk cytogenetics, ISS stage III MM, baseline bone marrow cells ≥60%, and baseline plasmacytomas. In patients with ISS stage III and with baseline plasmacytomas, median DOR appeared shorter and 18-mo PFS and OS rates lower. Cilta-cel safety profile across the subgroups was consistent with the overall population, with no new safety signals. Ongoing evaluation of cilta-cel in the multicohort CARTITUDE-2 (NCT04133636) study in pts with unmet need in varying stages of treatment for MM will further explore the treatment benefit of cilta-cel, including in those with high-risk disease. Figure 1 Figure 1. Disclosures Jakubowiak: GSK: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Gracell: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Usmani: Janssen Oncology: Consultancy, Research Funding; Takeda: Consultancy, Research Funding, Speakers Bureau; SkylineDX: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding, Speakers Bureau; Amgen: Consultancy, Research Funding, Speakers Bureau; Merck: Consultancy, Research Funding; Janssen: Consultancy, Research Funding, Speakers Bureau; Array BioPharma: Consultancy, Research Funding; GSK: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Celgene/BMS: Consultancy, Research Funding, Speakers Bureau; EdoPharma: Consultancy; Abbvie: Consultancy; Bristol-Myers Squibb: Research Funding. Berdeja: Bluebird bio, BMS, Celgene, CRISPR Therapeutics, Janssen, Kite Pharma, Legend Biotech, SecuraBio, Takeda: Consultancy; GSK, Ichnos Sciences, Incyte: Research Funding; EMD Sorono, Genentech: Research Funding; Celularity, CRISPR Therapeutics: Research Funding; Lilly, Novartis: Research Funding; Abbvie, Acetylon, Amgen: Research Funding; Poseida, Sanofi, Teva: Research Funding. Cohen: Oncopeptides: Consultancy; Genentech/Roche: Consultancy; Janssen: Consultancy; BMS/Celgene: Consultancy; Takeda: Consultancy; GlaxoSmithKline: Consultancy, Research Funding; AstraZeneca: Consultancy; Novartis: Research Funding. Hari: Karyopharm: Consultancy; Adaptive Biotech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millenium: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau; Celgene-BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Schecter: Janssen: Current Employment, Current holder of stock options in a privately-held company. Yeh: Janssen: Current Employment. Olyslager: Janssen: Current Employment. Banerjee: Janssen: Current Employment, Current holder of individual stocks in a privately-held company. Jackson: Janssen: Current Employment; Memorial Sloan Kettering Cancer Center: Consultancy. Allred: Janssen: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Zudaire: Janssen: Current Employment. Deraedt: Janssen: Current Employment. Geng: Legend Biotech USA: Current Employment. Pacaud: Legend Biotech: Current Employment. Lin: Janssen: Consultancy, Research Funding; Vineti: Consultancy; Legend: Consultancy; Bluebird Bio: Consultancy, Research Funding; Novartis: Consultancy; Juno: Consultancy; Celgene: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Takeda: Research Funding; Sorrento: Consultancy; Merck: Research Funding; Gamida Cell: Consultancy. Martin: Janssen: Research Funding; GlaxoSmithKline: Consultancy; Oncopeptides: Consultancy; Amgen: Research Funding; Sanofi: Research Funding. Jagannath: Bristol Myers Squibb: Consultancy; Janssen Pharmaceuticals: Consultancy; Legend Biotech: Consultancy; Karyopharm Therapeutics: Consultancy; Takeda: Consultancy; Sanofi: Consultancy. OffLabel Disclosure: At the time of abstract submission, cilta-cel is being investigated for the treatment of multiple myeloma but is not yet approved.

8005 Background: CARTITUDE-1 (NCT03548207) is a phase 1b/2 study evaluating ciltacabtagene autoleucel (cilta-cel; JNJ-68284528), a CAR T-cell therapy with two BCMA–targeting single-domain antibodies, in patients (pts) with R/R MM. Here, we report updated results in pts with a longer duration (median 12.4 months) of follow-up. Methods: Eligible pts had MM and received ≥3 prior regimens or were double refractory to a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), and had received a PI, IMiD, and anti-CD38 antibody. After apheresis, bridging therapy was permitted. Pts received a single cilta-cel infusion (target dose: 0.75×106 CAR+ viable T cells/kg; range 0.5-1.0×106) 5–7 days (d) after lymphodepletion (300 mg/m2 cyclophosphamide, 30 mg/m2 fludarabine daily for 3 d). The primary objectives were to characterize cilta-cel safety, confirm the recommended phase 2 dose (RP2D; phase 1b), and evaluate efficacy (phase 2). Cytokine release syndrome (CRS) was graded by Lee et al (Blood 2014) and neurotoxicity by CTCAE, v5.0 (in phase 1b). CRS and ICANS were graded by ASTCT criteria (in phase 2). Here, Lee et al and CTCAE v5.0 were mapped to ASTCT for CRS and ICANS, respectively. Results: As of Sept 1, 2020, 97 pts with a median of 6 prior lines received cilta-cel. Overall response rate per independent review committee (primary endpoint) was 97% (95% CI, 91–99), with 67% achieving stringent complete response (sCR). Median time to first response was 1 month (range, 1–9), and median time to CR or better was 2 months (range, 1–15). Responses deepened over time, and median duration of response was not reached. Of 57 pts evaluable for minimal residual disease (MRD) assessment, 93% were MRD-negative at 10-5. The 12-month progression-free survival (PFS) and overall survival rates (95% CI) were 77% (66–84) and 89% (80–94), respectively; median PFS was not reached. Grade 3/4 hematologic AEs ≥20% included neutropenia (95%), anemia (68%), leukopenia (61%), thrombocytopenia (60%), and lymphopenia (50%). CRS occurred in 95% of pts (4% grade 3/4), with median time to onset of 7 d (range, 1–12), and median duration of 4 d (range, 1–14, excluding 1 pt with 97-d duration). CRS resolved in all but one with grade 5 CRS/haemophagocytic lymphohistiocytosis. CAR T-cell neurotoxicity occurred in 21% of pts (grade ≥3, 10%). Fourteen deaths occurred during the study after cilta-cel infusion: none within the first 30 days, 2 within 100 days; and 12 more than 100 days post infusion, of which 5 were due to disease progression, and 4 due to treatment-related AEs. Conclusions: A single infusion of cilta-cel yielded early, deep, and durable responses in heavily pretreated pts with MM, with a manageable safety profile at the RP2D. Cilta-cel is under further investigation in other MM populations in earlier lines of therapy and in outpatient settings. Clinical trial information: NCT03548207.

Background: The phase 1b/2 CARTITUDE-1 study (NCT03548207) is evaluating ciltacabtagene autoleucel (cilta-cel; JNJ-68284528; LCAR-B38M CAR-T cells), a chimeric antigen receptor T (CAR-T) cell therapy with 2 B-cell maturation antigen-targeting single-domain antibodies, in patients with relapsed/refractory (R/R) multiple myeloma (MM). Cytokine release syndrome (CRS), a known side effect of CAR-T therapy, can be mild to life-threatening and requires careful monitoring and management. Here, we analyzed CRS and cytokine profiles in CARTITUDE-1. Methods: Eligible patients (aged ≥18 years) had a diagnosis of MM per International Myeloma Working Group criteria, measurable disease, Eastern Cooperative Oncology Group performance status ≤1, received ≥3 prior regimens or were double-refractory to a proteasome inhibitor and immunomodulatory drug, and received an anti-CD38 antibody. Bridging therapy was permitted after apheresis. At 5-7 days prior to cilta-cel infusion, lymphodepletion was performed with cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2 daily for 3 days. Cilta-cel was administered as a single infusion at a target dose of 0.75×106 (range: 0.5-1.0×106) CAR+ viable T cells/kg. CRS was graded using Lee et al (Blood 2014) in the phase 1b portion and American Society for Transplantation and Cellular Therapy (ASTCT) in the phase 2 portion. In this combined analysis, Lee et al criteria were mapped to ASTCT criteria for patients in the phase 1b portion. Serum samples for cytokine profiling were collected prior to lymphodepletion, prior to cilta-cel infusion and 2 hours post-infusion on Day 1, at regular time points until Day 100, and if CRS was suspected or reported. Results: A total of 97 patients with R/R MM were treated with cilta-cel; median follow-up for this analysis was 8.8 months (range: 1.5-20.4). CRS was reported in 92 (94.8%) patients. A total of 48 (49.5%) patients had grade 1 CRS, 38 (39.2%) had grade 2, 4 (4.1%) had grade 3, and 1 had grade 5 (1.0%); maximum toxicity grade according to the ASTCT consensus grading system could not be derived for 1 patient with CRS in the phase 1b portion. Median time to CRS onset from cilta-cel infusion was 7.0 days (range: 1-12). Median duration of CRS was 4.0 days (range: 1-27, excluding n=1 with 97 days). Supportive measures to treat CRS or CRS symptoms were administered to 87 (89.7%) patients, most commonly tocilizumab (69.1%), acetaminophen (68.0%), corticosteroids (20.6%), and anakinra (18.6%). CRS resolved in 91 (98.9%) patients; the patient with grade 5 CRS/hemophagocytic lymphohistiocytosis died on Day 99 subsequent to sequelae of grade 4 CRS. Across all patients, levels of interleukin (IL)-6, IL-10, and interferon-γ peaked at Days 7-14 post-cilta-cel infusion. Conclusions: CRS after cilta-cel treatment was low grade and manageable in most patients with R/R MM. The low rate of grade ≥3 CRS, median time to CRS onset of 7.0 days, and median duration of 4.0 days suggests outpatient dosing of cilta-cel may be feasible; this approach is being explored in the phase 2 CARTITUDE-2 study (NCT04133636). Disclosures Lin: Gamida Cells: Consultancy; Sorrento: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite, a Gilead Company: Consultancy, Research Funding; Vineti: Consultancy; Takeda: Research Funding; Merck: Research Funding; Legend BioTech: Consultancy; Juno: Consultancy; Bluebird Bio: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy; Janssen: Consultancy, Research Funding. Martin:Janssen: Research Funding; AMGEN: Research Funding; Sanofi: Research Funding; Seattle Genetics: Research Funding; GSK: Consultancy. Cohen:Novartis: Other: Patents/Intellectual property licensed, Research Funding; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda,: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Genentech/Roche: Membership on an entity's Board of Directors or advisory committees. Jakubowiak:AbbVie, Amgen, BMS/Celgene, GSK, Janssen, Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive, Juno: Consultancy, Honoraria. Usmani:Celgene: Other; Takeda: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; SkylineDX: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Pharmacyclics: Research Funding; GSK: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Array Biopharma: Research Funding; Merck: Consultancy, Research Funding; Abbvie: Consultancy; BMS, Celgene: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Amgen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Incyte: Research Funding. Madduri:AbbVie: Consultancy, Honoraria; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; Foundation Medicine: Consultancy, Honoraria; Legend: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Kinevant: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau. Stewart:Janssen, BMS, Sanofi-Aventis, GSK: Honoraria; Tempus, Inc., Genomics England LLC: Membership on an entity's Board of Directors or advisory committees. Singh:Janssen: Current Employment. Zudaire:Janssen: Current Employment. Yeh:Janssen: Current Employment. Allred:Janssen: Current Employment. Olyslager:Janssen: Current Employment. Banerjee:Janssen: Current Employment. Goldberg:Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Schecter:Janssen: Current Employment. Jackson:Memorial Sloan Kettering Cancer Center: Consultancy; Janssen: Current Employment. Deraedt:Janssen: Current Employment, Current equity holder in publicly-traded company. Geng:Legend Biotech USA Inc.: Current Employment. Wu:Legend Biotech USA Inc.: Current Employment. Carrasco:Legend Biotech USA Inc.: Current Employment. Akram:Legend Biotech USA Inc.: Current Employment. Hossain:Legend Biotech USA Inc.: Current Employment. Wang:Legend Biotech USA Inc.: Current Employment. Berdeja:CRISPR Therapeutics: Consultancy, Research Funding; EMD Sorono: Research Funding; Teva: Research Funding; Servier: Consultancy; Vivolux: Research Funding; Abbvie: Research Funding; Novartis: Research Funding; Janssen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Karyopharm: Consultancy; Kesios: Research Funding; Kite Pharma: Consultancy; Legend: Consultancy; Genentech, Inc.: Research Funding; BMS: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Cellularity: Research Funding; Constellation: Research Funding; Glenmark: Research Funding; CURIS: Research Funding; Bioclinica: Consultancy; Amgen: Consultancy, Research Funding; Bluebird: Research Funding; Poseida: Research Funding; Acetylon: Research Funding; Prothena: Consultancy; Lilly: Research Funding. Jagannath:BMS, Janssen, Karyopharm, Legend Biotech, Sanofi, Takeda: Consultancy.

Background: Multiple myeloma (MM) negatively affects health-related quality of life (HRQoL), and with each relapse, patients with MM experience further declines in HRQoL. Patient-reported HRQoL is therefore an important treatment outcome, in addition to clinical response to therapy. CARTITUDE-1 (NCT03548207) is a phase 1b/2 study evaluating the safety and efficacy of ciltacabtagene autoleucel (cilta-cel; JNJ-68284528; LCAR-B38M CAR-T cells), a chimeric antigen receptor T (CAR-T) cell therapy with 2 B-cell maturation antigen-targeting single-domain antibodies, in patients with relapsed/refractory (R/R) MM. We evaluated symptoms, functioning, and overall HRQoL through patient-reported outcome measures, which is a secondary objective of CARTITUDE-1. Methods: Patients were ≥18 years of age with a diagnosis of MM per International Myeloma Working Group criteria, measurable disease, and Eastern Cooperative Oncology Group performance status ≤1. Patients had received ≥3 prior regimens for MM or were double-refractory to a proteasome inhibitor and immunomodulatory drug, and had received an anti-CD38 antibody. Cilta-cel was given as a single infusion on Day 1 (target dose: 0.75×106 [range: 0.5-1.0×106] CAR+ viable T cells/kg) 5-7 days after start of lymphodepletion (cyclophosphamide 300 mg/m2 + fludarabine 30 mg/m2 daily for 3 days). In the phase 2 portion of CARTITUDE-1, HRQoL was assessed at baseline, on Days 7, 28, 56, 78, and 100, and every 28 days thereafter using 3 patient-reported instruments: the European Organization for Research and Treatment of Cancer QoL Questionnaire Core 30 (EORTC QLQ-C30), 4 items from the EORTC QLQ-Multiple Myeloma (MY20) module, and the 5-level EuroQol Five Dimension (EQ-5D-5L) measure. Raw EORTC QLQ-C30 and EORTC QLQ-MY20 scores were linearly transformed to a scale ranging from 0 to 100; the EQ-5D-5L visual analog scale (VAS) score ranges from 0 to 100. Clinically meaningful changes in EORTC QLQ-C30 symptoms, physical functioning, and overall HRQoL were based on anchor-based methods using a patient global impression of change item. Repeated-measures mixed-effects models were used to analyze mean changes in HRQoL from baseline to subsequent assessment time points in patients in the modified intent-to-treat population with ≥1 post-baseline assessment. Median time to event of HRQoL scores was calculated descriptively, using a change in score ≥0.5×standard deviation of values prior to cilta-cel infusion as improvement/worsening with death due to progression defined as worsening. Results: For the 68 patients in the phase 2 portion of CARTITUDE-1 (63.2% male; median age: 62.0 years [range: 43-78]), questionnaire completion rates at baseline and Day 100, respectively, were 92.6% and 69.2% for both the EORTC QLQ-C30 and EORTC QLQ-MY20 items and 92.6% and 70.8% for the EQ-5D-5L. For EORTC QLQ-C30 subscales, clinically meaningful improvements at Day 100 were seen for 71.1% of patients for pain, 62.2% for fatigue, 72.1% for physical functioning, and 51.1% for global health status. Mean changes in pain and fatigue showed a reduction in these symptoms over time (following an initial worsening of fatigue at Day 7; Figure). This trend of improvements over time was also observed for overall HRQoL and EORTC QLQ-MY20 single items. Clinically meaningful improvements at Day 100, defined by a literature-based minimal important difference of 10 points in mean score, were observed for the EORTC QLQ-MY20 single items: thinking about illness and worries about dying or future health. Approximately 50% of the population reported an event of improvement or worsening in EORTC QLQ-C30 and EQ-5D-5L scales, with the rest censored in this early data cut; among these patients, median time to improvement was approximately 1-2 months (with median time to worsening occurring less than 1 month after cilta-cel treatment). There was a trend for an improvement in mean EORTC QLQ-C30 global health status, physical functioning, pain, and fatigue, and EQ-5D-5L VAS at Day 100 with increased depth of response. Conclusions: Some patients with heavily pretreated MM showed rapid and clinically meaningful improvements in pain, fatigue, physical functioning, overall HRQoL, and future perspectives, consistent with their clinical outcomes. With additional follow-up, it is possible that these early improvements in symptoms will translate into greater improvement in overall HRQoL in the long term. Disclosures Martin: Janssen: Research Funding; Sanofi: Research Funding; AMGEN: Research Funding; Seattle Genetics: Research Funding; GSK: Consultancy. Lin:Vineti: Consultancy; Janssen: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy; Legend BioTech: Consultancy; Bluebird Bio: Consultancy, Research Funding; Juno: Consultancy; Merck: Research Funding; Takeda: Research Funding; Gamida Cells: Consultancy; Sorrento: Consultancy, Membership on an entity's Board of Directors or advisory committees. Cohen:Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda,: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Novartis: Other: Patents/Intellectual property licensed, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Genentech/Roche: Membership on an entity's Board of Directors or advisory committees. Htut:City of Hope Medical Center: Current Employment. Stewart:Janssen, BMS, Sanofi-Aventis, GSK: Honoraria; Tempus, Inc., Genomics England LLC: Membership on an entity's Board of Directors or advisory committees. Hari:GSK: Consultancy; BMS: Consultancy; Takeda: Consultancy; Amgen: Consultancy; Incyte Corporation: Consultancy; Janssen: Consultancy. Berdeja:Teva: Research Funding; Cellularity: Research Funding; Kesios: Research Funding; BMS: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; CURIS: Research Funding; EMD Sorono: Research Funding; Genentech, Inc.: Research Funding; Karyopharm: Consultancy; Poseida: Research Funding; Novartis: Research Funding; Lilly: Research Funding; Amgen: Consultancy, Research Funding; Acetylon: Research Funding; Glenmark: Research Funding; Janssen: Consultancy, Research Funding; Vivolux: Research Funding; Takeda: Consultancy, Research Funding; Servier: Consultancy; CRISPR Therapeutics: Consultancy, Research Funding; Constellation: Research Funding; Bluebird: Research Funding; Abbvie: Research Funding; Prothena: Consultancy; Bioclinica: Consultancy; Kite Pharma: Consultancy; Legend: Consultancy. Madduri:Foundation Medicine: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; AbbVie: Consultancy, Honoraria; Legend: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; Kinevant: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; Celgene: Consultancy, Honoraria. Usmani:Takeda: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; SkylineDX: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Incyte: Research Funding; Pharmacyclics: Research Funding; Janssen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; GSK: Consultancy, Research Funding; Abbvie: Consultancy; Array Biopharma: Research Funding; Celgene: Other; Amgen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; BMS, Celgene: Consultancy, Honoraria, Other: Speaking Fees, Research Funding. Yeh:Janssen: Current Employment. Allred:Janssen: Current Employment. Olyslager:Janssen: Current Employment. Banerjee:Janssen: Current Employment. Goldberg:Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Schecter:Janssen: Current Employment. Jackson:Janssen: Current Employment; Memorial Sloan Kettering Cancer Center: Consultancy. Deraedt:Janssen: Current Employment, Current equity holder in publicly-traded company. Gries:Janssen: Current Employment, Current equity holder in publicly-traded company. Fastenau:Janssen: Current Employment, Current equity holder in publicly-traded company. Wu:Legend Biotech USA Inc.: Current Employment. Carrasco:Legend Biotech USA Inc.: Current Employment. Akram:Legend Biotech USA Inc.: Current Employment. Hossain:Legend Biotech USA Inc.: Current Employment. Jakubowiak:AbbVie, Amgen, BMS/Celgene, GSK, Janssen, Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive, Juno: Consultancy, Honoraria. Jagannath:BMS, Janssen, Karyopharm, Legend Biotech, Sanofi, Takeda: Consultancy.

Aims: To evaluate AMG 701, a BiTE® molecule binding BCMA on MM cells and CD3 on T cells, in RR MM (Amgen, NCT03287908); primary objective was to evaluate safety and tolerability and estimate a biologically active dose; secondary objectives were to characterize pharmacokinetics (PK), anti-myeloma activity per IMWG criteria, and response duration. Methods: Patients with MM RR or intolerant to ≥3 lines [proteasome inhibitor (PI), IMiD, anti-CD38 Ab as available] received AMG 701 IV infusions weekly in 4-week cycles until disease progression (PD). A 0.8-mg step dose was added prior to target doses ≥1.2 mg to prevent severe cytokine release syndrome (CRS). Target dose was achieved by day 8 or sooner with earlier escalation. Exclusion criteria included: solely extramedullary disease; prior allogeneic stem cell transplant (SCT) in the past 6 months; prior autologous SCT in the past 90 days; CNS involvement; prior anti-BCMA therapy. The first 3 cohorts (dose 5-45 μg) had 1 patient each, the next cohorts (0.14-1.2 mg) had 3-4 patients each, and subsequent cohorts (1.6-12 mg) were to have 3-10 patients each. Minimal residual disease (MRD) was measured by next-generation sequencing (NGS, ≤10-5 per IMWG) or flow cytometry (≤3×10-5). Results: As of July 2, 2020, 75 patients received AMG 701. Patients had a median age of 63 years, a median time since diagnosis of 5.9 years, and a median (range) of 6 (1-25) prior lines of therapy; 27% of patients had extramedullary disease, 83% prior SCT, and 93% prior anti-CD38 Ab; 68% were triple refractory to a PI, an IMiD, and an anti-CD38 Ab. Median (Q1, Q3) treatment duration was 6.1 (3.1, 15.3) weeks and median follow-up on treatment was 1.7 (1.0, 3.7) months. Patients discontinued drug for PD (n=47), AEs (adverse events, n=4, 3 CRS, 1 CMV / PCP pneumonia), withdrew consent (4), other therapy (1), investigator discretion (1), and CNS disease (1); 17 patients remain on AMG 701. The most common hematological AEs were anemia (43%), neutropenia (23%), and thrombocytopenia (20%). The most common non-hematological AEs were CRS (61%), diarrhea (31%), fatigue (25%), and fever (25%). CRS was mostly grade 1 (n=19) or 2 (n=21) per Lee Blood 2014 criteria. All grade 3 CRS (n=5, 7%) were assessed as dose-limiting toxicities (DLTs); all were reversible with corticosteroids and tocilizumab, with median duration of 2 days. CRS grade 3 drivers included transient LFT increases in 3 patients and hypoxia in 2 patients. Other DLTs were 1 case each of transient grade 3 atrial fibrillation, transient grade 3 acidosis, and grade 4 thrombocytopenia. Serious AEs (n=29, 39%) included infections (13), CRS (7), and asymptomatic pancreatic enzyme rise (2, no imaging changes, 1 treatment related). There were 4 deaths from AEs, none related to AMG 701 (2 cases of sepsis, 1 of retroperitoneal bleeding, and 1 of subdural hematoma). Reversible treatment-related neurotoxicity was seen in 6 patients, with median duration of 1 day, all grade 1-2, and associated with CRS in 4 patients. The response rate was 36% (16/45) at doses of 3-12 mg; at ≤1.6 mg (n=27), there was 1 response at 0.8 mg in a patient with low baseline soluble BCMA (sBCMA). With earlier dose escalation with 9 mg, the response rate was 83% (5/6, 3 PRs, 2 VGPRs), with 4/5 responders being triple refractory and 1 DLT of grade 3 CRS in this group. Across the study, responses included 4 stringent CRs (3 MRD-negative, 1 not yet tested), 1 MRD-negative CR, 6 VGPRs, and 6 PRs (Table). Median (Q1, Q3) time to response was 1.0 (1.0, 1.9) month, time to best response was 2.8 (1.0, 3.7) months, and response duration was 3.8 (1.9, 7.4) months, with maximum duration of 23 months; responses were ongoing at last assessment in 14/17 patients (Figure). MRD was tested in 4 patients (3 sCR, 1 CR) and all were negative (3 by NGS, 1 by flow); MRD negativity was ongoing at last observations up to 20 months later. AMG 701 exhibited a favorable PK profile in its target patient population of RR MM, with AMG 701 exposures increasing in a dose-related manner. Patient baseline sBCMA levels were identified as a determinant of AMG 701 free drug exposures; at higher doses, encouraging preliminary responses were seen even at the higher end of baseline sBCMA values. Summary: In this FIH study with ongoing dose escalation, AMG 701, an anti-BCMA BiTE® molecule, demonstrated a manageable safety profile, encouraging activity, and a favorable PK profile in patients with heavily pre-treated RR MM, supporting further evaluation of AMG 701. Disclosures Harrison: Janssen: Honoraria; Novartis: Consultancy, Honoraria, Patents & Royalties: wrt panobinostat; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria; CRISPR Therapeutics: Consultancy, Honoraria; Haemalogix: Consultancy; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; F. Hoffmann-La Roche: Consultancy, Honoraria. Minnema:Amgen: Honoraria; Servier: Honoraria; Gilead: Honoraria; Celgene Corporation: Honoraria, Research Funding; Janssen Cilag: Honoraria. Lee:Celgene: Consultancy, Research Funding; Genentech: Consultancy; GlaxoSmithKline: Consultancy, Research Funding; Genentech: Consultancy; Regeneron: Research Funding; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Sanofi: Consultancy; Daiichi Sankyo: Research Funding; Amgen: Consultancy, Research Funding. Spencer:AbbVie: Consultancy, Honoraria, Research Funding; Roche: Honoraria; Takeda: Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Secura Bio: Consultancy, Honoraria; Servier: Consultancy, Honoraria, Research Funding; HaemaLogiX: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pfizer: Consultancy, Honoraria; Pharmamar: Research Funding. Kapoor:Cellectar: Consultancy; Amgen: Research Funding; Janssen: Research Funding; Sanofi: Consultancy, Research Funding; Takeda: Honoraria, Research Funding; GlaxoSmithKline: Research Funding; Celgene: Honoraria. Madduri:Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Foundation Medicine: Consultancy, Honoraria; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; Kinevant: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; Legend: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; Celgene: Consultancy, Honoraria. Larsen:Janssen Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Ailawadhi:Cellectar: Research Funding; BMS: Research Funding; Medimmune: Research Funding; Amgen: Research Funding; Takeda: Honoraria; Janssen: Research Funding; Pharmacyclics: Research Funding; Celgene: Honoraria; Phosplatin: Research Funding. Kaufman:Amgen: Consultancy, Honoraria; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Honoraria; AbbVie: Consultancy; Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Tecnopharma: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi/Genyzme: Consultancy, Honoraria. Raab:Takeda: Membership on an entity's Board of Directors or advisory committees; Heidelberg Pharma: Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees, Research Funding. Hari:BMS: Consultancy; Amgen: Consultancy; GSK: Consultancy; Janssen: Consultancy; Incyte Corporation: Consultancy; Takeda: Consultancy. Iida:AbbVie: Research Funding; Merck Sharpe Dohme: Research Funding; Kyowa Kirin: Research Funding; Chugai: Research Funding; Sanofi: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Ono: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Davies:Celgene/BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotech: Honoraria; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees. Lesley:Amgen Inc.: Current Employment, Current equity holder in publicly-traded company. Upreti:Amgen Inc.: Current Employment, Current equity holder in publicly-traded company. Yang:Amgen Inc.: Current Employment, Current equity holder in publicly-traded company. Sharma:Amgen Inc.: Current Employment, Current equity holder in publicly-traded company. Minella:Amgen Inc.: Current equity holder in publicly-traded company, Ended employment in the past 24 months; Beam Therapeutics Inc.: Current Employment, Current equity holder in publicly-traded company. Lentzsch:Mesoblast: Divested equity in a private or publicly-traded company in the past 24 months; Janssen: Consultancy; Caelum Biosciences: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Magenta: Current equity holder in private company; Sanofi: Research Funding; Karyopharm: Research Funding; Celularity: Consultancy; Sorrento: Consultancy. OffLabel Disclosure: AMG 701, a half-life extended BiTE® (bispecific T-cell engager) molecule is an investigational agent for multiple myeloma.

Background: Ciltacabtagene autoleucel (cilta-cel; JNJ-68284528; LCAR-B38M CAR-T cells) is a chimeric antigen receptor T (CAR-T) cell therapy with 2 B-cell maturation antigen-targeting single-domain antibodies designed to confer avidity. In the phase 1 LEGEND-2 study in China, LCAR-B38M yielded deep, durable responses with a manageable safety profile in patients (pts) with relapsed/refractory multiple myeloma (R/R MM). The phase 1b/2 CARTITUDE-1 study (NCT03548207) is further evaluating cilta-cel in this pt population in the US. We present updated data from the phase 1b portion along with initial phase 2 data. Methods: Eligible pts (aged ≥18 y) were diagnosed with MM per International Myeloma Working Group (IMWG) criteria and had measurable disease, Eastern Cooperative Oncology Group performance status ≤1, received ≥3 prior regimens or were double-refractory to a proteasome inhibitor and immunomodulatory drug, and received an anti-CD38 antibody. After apheresis, bridging therapy was permitted. Cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2 daily for 3 d were used for lymphodepletion. A single infusion of cilta-cel at a target dose of 0.75×106 (range 0.5-1.0×106) CAR+ viable T cells/kg was administered 5-7 d after start of lymphodepletion. The primary objective of the phase 1b portion was to characterize cilta-cel safety and establish the recommended phase 2 dose; the primary objective of the phase 2 portion was to evaluate cilta-cel efficacy. Response was assessed per IMWG criteria and minimal residual disease (MRD) by next-generation sequencing. Adverse events (AEs) were graded using CTCAE v5.0. In the phase 1b portion, cytokine release syndrome (CRS) was graded by Lee et al (Blood 2014) and neurotoxicity by CTCAE v5.0; in the phase 2 portion, CRS and neurotoxicity were graded by American Society for Transplantation and Cellular Therapy (ASTCT) criteria. In this combined analysis, Lee et al and CTCAE v5.0 were mapped to ASTCT criteria for CRS and immune effector cell-associated neurotoxicity syndrome (ICANS), respectively. Results: As of the May 20, 2020 clinical cutoff, 97 pts (58.8% male; median age 61.0 y [range 43-78]) with R/R MM received cilta-cel (29 in phase 1b; 68 in phase 2). Median follow-up duration was 8.8 mo (range 1.5-20.4). Pts had received a median of 6 prior lines of therapy (range 3-18); 83.5% were penta-exposed, 87.6% were triple-refractory, 41.2% were penta-refractory, and 97.9% were refractory to last line of therapy. Overall response rate per independent review committee (primary endpoint) was 94.8% (95% CI 88.4-98.3), with a stringent complete response rate of 55.7% (95% CI 45.2-65.8), very good partial response rate of 32.0% (95% CI 22.9-42.2), and partial response rate of 7.2% (95% CI 3.0-14.3). All pts achieved a reduction in M-protein. Median time to first response was 1.0 mo (range 0.9-5.8; 80.4% ≤1.0 mo), and median time to complete response or better was 1.8 mo (range 0.9-12.5; 74.1% ≤3.0 mo); responses deepened over time (Figure). Median duration of response was not reached (NR). Of 52 MRD-evaluable pts, 94.2% were MRD-negative at 10-5. The 6-mo progression-free survival (PFS) and overall survival (OS) rates (95% CI) were 87.4% (78.9-92.7) and 93.8% (86.7-97.2), respectively; median PFS and OS were NR. Ten deaths occurred during the study; 8 were due to AEs (both related and unrelated; CRS/hemophagocytic lymphohistiocytosis, neurotoxicity, respiratory failure, sepsis, septic shock, pneumonia, lung abscess, and acute myelogenous leukemia [n=1 each]), and 2 due to progressive disease. AEs reported in >70% of pts were CRS (94.8%; grade [gr] 3/4 4.1%), neutropenia (90.7%; gr 3/4 90.7%), anemia (81.4%; gr 3/4 68.0%), and thrombocytopenia (79.4%; gr 3/4 59.8%). Median time to CRS onset was 7.0 d (range 1-12) and median duration 4.0 d (range 1-27, excluding n=1 with 97 d). CAR-T cell-related neurotoxicity was reported in 20.6% of pts (gr 3/4 10.3%). Cilta-cel CAR+ T cells showed maximum peripheral expansion at 14 d (range 9-43). Among pts with 6 mo' individual follow-up, 67% had cilta-cel CAR+ T cells below the level of quantification (2 cells/µL) in peripheral blood. Conclusions: Preliminary phase 1b/2 data from CARTITUDE-1 indicate a single low-dose infusion of cilta-cel leads to early, deep, and durable responses in heavily pretreated pts with MM with a safety profile consistent with LEGEND-2. Further investigation of cilta-cel in other MM populations is underway. Disclosures Madduri: Celgene: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Foundation Medicine: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Legend: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; Kinevant: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau. Berdeja:Teva: Research Funding; Bluebird: Research Funding; Bioclinica: Consultancy; Celgene: Consultancy, Research Funding; EMD Sorono: Research Funding; Kite Pharma: Consultancy; Prothena: Consultancy; Cellularity: Research Funding; Karyopharm: Consultancy; Servier: Consultancy; Legend: Consultancy; Poseida: Research Funding; Lilly: Research Funding; Acetylon: Research Funding; CURIS: Research Funding; Janssen: Consultancy, Research Funding; Genentech, Inc.: Research Funding; Glenmark: Research Funding; Takeda: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Constellation: Research Funding; CRISPR Therapeutics: Consultancy, Research Funding; Vivolux: Research Funding; Abbvie: Research Funding; Amgen: Consultancy, Research Funding; Kesios: Research Funding; Novartis: Research Funding. Usmani:Celgene: Other; BMS, Celgene: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; GSK: Consultancy, Research Funding; Pharmacyclics: Research Funding; Merck: Consultancy, Research Funding; Abbvie: Consultancy; Sanofi: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Janssen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; SkylineDX: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Incyte: Research Funding; Array Biopharma: Research Funding; Amgen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding. Jakubowiak:Adaptive, Juno: Consultancy, Honoraria; AbbVie, Amgen, BMS/Celgene, GSK, Janssen, Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Cohen:Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda,: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Genentech/Roche: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Other: Patents/Intellectual property licensed, Research Funding. Stewart:Janssen, BMS, Sanofi-Aventis, GSK: Honoraria; Tempus, Inc., Genomics England LLC: Membership on an entity's Board of Directors or advisory committees. Hari:Amgen: Consultancy; BMS: Consultancy; GSK: Consultancy; Janssen: Consultancy; Takeda: Consultancy; Incyte Corporation: Consultancy. Htut:City of Hope Medical Center: Current Employment. Munshi:OncoPep: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; BMS: Consultancy; Janssen: Consultancy; Adaptive: Consultancy; Legend: Consultancy; Amgen: Consultancy; Karyopharm: Consultancy; Takeda: Consultancy; AbbVie: Consultancy; C4: Current equity holder in private company. Deol:Novartis: Consultancy; Kite, a Gilead Company: Consultancy. Lesokhin:BMS: Consultancy, Honoraria, Research Funding; Genentech: Research Funding; Janssen: Research Funding; Juno: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Serametrix Inc.: Patents & Royalties; GenMab: Consultancy, Honoraria. Singh:Janssen: Current Employment. Zudaire:Janssen: Current Employment. Yeh:Janssen: Current Employment. Allred:Janssen: Current Employment. Olyslager:Janssen: Current Employment. Banerjee:Janssen: Current Employment. Goldberg:Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Schecter:Janssen: Current Employment. Jackson:Janssen: Current Employment; Memorial Sloan Kettering Cancer Center: Consultancy. Deraedt:Janssen: Current Employment, Current equity holder in publicly-traded company. Zhuang:Janssen: Current Employment. Infante:Janssen: Current Employment. Geng:Legend Biotech USA Inc.: Current Employment. Wu:Legend Biotech USA Inc.: Current Employment. Carrasco:Legend Biotech USA Inc.: Current Employment. Akram:Legend Biotech USA Inc.: Current Employment. Hossain:Legend Biotech USA Inc.: Current Employment. Rizvi:Legend Biotech USA Inc.: Current Employment. Fan:Legend Biotech USA Inc.: Current Employment. Jagannath:BMS, Janssen, Karyopharm, Legend Biotech, Sanofi, Takeda: Consultancy. Lin:Kite, a Gilead Company: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Merck: Research Funding; Legend BioTech: Consultancy; Juno: Consultancy; Bluebird Bio: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy; Vineti: Consultancy; Takeda: Research Funding; Gamida Cells: Consultancy; Sorrento: Consultancy, Membership on an entity's Board of Directors or advisory committees. Martin:AMGEN: Research Funding; Seattle Genetics: Research Funding; Janssen: Research Funding; GSK: Consultancy; Sanofi: Research Funding.

Background: Ide-cel, a BCMA-directed CAR T cell therapy, showed tolerability and promising efficacy in patients with relapsed and/or refractory multiple myeloma (RRMM) in the first-in-human phase 1 CRB-401 study (Raje et al. N Engl J Med. 2019;380:1726) and the pivotal phase 2 KarMMa study (Munshi et al. J Clin Oncol. 2020;38[suppl, abstr]:8503). Ide-cel demonstrated a favorable benefit-risk profile with an overall response rate (ORR) of 85%, a complete response (CR) rate of 45%, and a median progression-free survival (PFS) of 11.8 months in the first 33 patients treated in CRB-401. Reported here are updated safety and efficacy results for 62 patients who received ide-cel in the ongoing CRB-401 study. Methods: CRB-401 (NCT02658929) is a 2-part, phase 1 dose-escalation and -expansion study. The expansion phase enrolled patients who had received ≥3 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody, and were refractory to their last line of therapy. Eligibility criteria for the dose-escalation phase were described previously (Raje et al. N Engl J Med. 2019;380:1726). After lymphodepletion with fludarabine (30 mg/m2/day) and cyclophosphamide (300 mg/m2/day) for 3 days followed by 2 days of rest, patients received ide-cel at target doses of 50, 150, 450, or 800 × 106 CAR+ T cells in the dose-escalation phase and 150 to 450 × 106 CAR+ T cells in the dose-expansion phase. The primary endpoint was safety. Secondary endpoints included tumor response according to the International Myeloma Working Group criteria. Exploratory endpoints included PFS, overall survival (OS), and minimal residual disease (MRD). Results: As of January 14, 2020, 21 patients had received ide-cel in the dose-escalation phase, and 41 patients received ide-cel in the dose-expansion phase. The median age was 61 years, and 44% of patients had high tumor burden (≥50% bone marrow CD138+ plasma cells). Of the 62 patients, 45% received >6 prior regimens, 90% were daratumumab-exposed, and 77% were daratumumab-refractory. As of the cutoff date, 13 patients were ongoing, and 49 patients had discontinued the study. Reasons for study discontinuation were progressive disease (58%), withdrawal by patients (10%), and death (10%). Based on safety and efficacy in the dose-escalation phase, target dose levels of 150 to 450 × 106 CAR+ T cells were selected for the dose-expansion phase. The most frequent adverse events (AEs) were neutropenia (92%), cytokine release syndrome (CRS; 76%), anemia (76%), and thrombocytopenia (74%). The most frequent grade 3/4 AEs were neutropenia (89%), leukopenia (61%), anemia (57%), and thrombocytopenia (57%). Most CRS events were grade 1 or 2 (Table). Four patients (7%) had grade 3 CRS; there were no grade >3 CRS events. The incidence of CRS generally increased with target dose level. Neurologic toxicity (NT; clustered term) occurred in 27 patients (44%) and was primarily grade 1/2 with 1 patient having grade 3 and 1 patient having grade 4 NT. Among all 62 patients in the dose-escalation and -expansion phases, the ORR was 76%, including 24 patients (39%) with a CR or better and 40 patients (65%) with a very good partial response or better. The median duration of response was 10.3 months. Of 37 responders evaluable for MRD, 30 were MRD negative (≤10−4 nucleated cells) at 1 or more time point, and 7 responders were MRD positive. With a median follow-up of 14.7 months for all patients in the dose-escalation and dose-expansion phases, median PFS was 8.8 months and median OS was 34.2 months. Overall, a dose-dependent effect was observed on responses and survival outcomes, with greater efficacy reported at ≥150 × 106 CAR+ T cells (Table). Conclusions: Ide-cel demonstrated deep and durable responses in heavily-pretreated RRMM patients. Efficacy and safety reflect prior reports and support a favorable clinical benefit-risk profile for ide-cel at target dose levels ≥150 × 106 CAR+ T cells. Table Disclosures Lin: Novartis: Consultancy; Janssen: Consultancy, Research Funding; Vineti: Consultancy; Sorrento: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gamida Cells: Consultancy; Takeda: Research Funding; Merck: Research Funding; Legend BioTech: Consultancy; Juno: Consultancy; Celgene: Consultancy, Research Funding; Bluebird Bio: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding. Raje:Caribou: Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy; Bluebird, Bio: Consultancy, Research Funding; Takeda: Consultancy; Immuneel: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; Karyopharm: Consultancy; Celgene: Consultancy; Astrazeneca: Consultancy; Amgen: Consultancy. Berdeja:Abbvie: Research Funding; BMS: Consultancy, Research Funding; Karyopharm: Consultancy; Vivolux: Research Funding; Genentech, Inc.: Research Funding; Bluebird: Research Funding; Lilly: Research Funding; Constellation: Research Funding; Glenmark: Research Funding; Janssen: Consultancy, Research Funding; Legend: Consultancy; Novartis: Research Funding; Poseida: Research Funding; Prothena: Consultancy; Teva: Research Funding; Servier: Consultancy; Takeda: Consultancy, Research Funding; Bioclinica: Consultancy; EMD Sorono: Research Funding; Acetylon: Research Funding; Celgene: Consultancy, Research Funding; Cellularity: Research Funding; Kesios: Research Funding; CURIS: Research Funding; Kite Pharma: Consultancy; CRISPR Therapeutics: Consultancy, Research Funding; Amgen: Consultancy, Research Funding. Siegel:Karyopharma: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Merck: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau; Celulatiry: Consultancy. Jagannath:Janssen: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Legend Biotech: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Madduri:Legend: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; Celgene: Consultancy, Honoraria; Kinevant: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau; Foundation Medicine: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaking Engagement, Speakers Bureau. Liedtke:Pfizer: Honoraria; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Caelum: Membership on an entity's Board of Directors or advisory committees; Adaptive: Membership on an entity's Board of Directors or advisory committees. Rosenblatt:Celgene: Research Funding. Maus:arcellx: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; kite: Consultancy, Research Funding. Massaro:bluebird, bio: Current Employment, Current equity holder in publicly-traded company. Petrocca:bluebird, bio: Current Employment, Current equity holder in publicly-traded company. Caia:Celgene a BMS company: Current Employment, Current equity holder in publicly-traded company. Yang:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company; Celgene: Ended employment in the past 24 months. Campbell:BMS: Current Employment, Current equity holder in publicly-traded company. Hege:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Patents & Royalties: numerous, Research Funding; Celgene (acquired by Bristol Myers Squibb): Ended employment in the past 24 months; Mersana Therapeutics: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Arcus Biosciences (Former Board of Directors): Divested equity in a private or publicly-traded company in the past 24 months. Munshi:BMS: Consultancy; OncoPep: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; AbbVie: Consultancy; Karyopharm: Consultancy; Takeda: Consultancy; Adaptive: Consultancy; Janssen: Consultancy; C4: Current equity holder in private company; Amgen: Consultancy; Legend: Consultancy. Kochenderfer:Celgene: Patents & Royalties, Research Funding; bluebird, bio: Patents & Royalties; Kite, a Gilead company: Patents & Royalties, Research Funding.