Citations

Abstract Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with a poor prognosis and considered incurable with conventional chemotherapy. Small observational studies reported allogeneic hematopoietic cell transplantation (allo-HCT) offers durable remissions in patients with BPDCN. We report an analysis of patients with BPDCN who received an allo-HCT, using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). We identified 164 patients with BPDCN from 78 centers who underwent allo-HCT between 2007 and 2018. The 5-year overall survival (OS), disease-free survival (DFS), relapse, and nonrelapse mortality (NRM) rates were 51.2% (95% confidence interval [CI], 42.5-59.8), 44.4% (95% CI, 36.2-52.8), 32.2% (95% CI, 24.7-40.3), and 23.3% (95% CI, 16.9-30.4), respectively. Disease relapse was the most common cause of death. On multivariate analyses, age of ≥60 years was predictive for inferior OS (hazard ratio [HR], 2.16; 95% CI, 1.35-3.46; P = .001), and higher NRM (HR, 2.19; 95% CI, 1.13-4.22; P = .02). Remission status at time of allo-HCT (CR2/primary induction failure/relapse vs CR1) was predictive of inferior OS (HR, 1.87; 95% CI, 1.14-3.06; P = .01) and DFS (HR, 1.75; 95% CI, 1.11-2.76; P = .02). Use of myeloablative conditioning with total body irradiation (MAC-TBI) was predictive of improved DFS and reduced relapse risk. Allo-HCT is effective in providing durable remissions and long-term survival in BPDCN. Younger age and allo-HCT in CR1 predicted for improved survival, whereas MAC-TBI predicted for less relapse and improved DFS. Novel strategies incorporating allo-HCT are needed to further improve outcomes.

8024 Background: Minimal residual disease (MRD) is prognostic for survival in multiple myeloma (MM). MRD is usually assessed in the bone marrow (BM) by flow cytometry or NGS. MRD by FDG PET/CT provides a global representation of the tumor burden, including response assessment of extramedullary disease. We examined MRD status in MM pts using both BM and PET/CT at Mayo Clinic. Methods: Medical records were reviewed retrospectively for MM pts who received CAR-T between 4/2018 and 12/2022. All PET/CT scans were assessed by radiologists. BM MRD was assessed by flow cytometry with a sensitivity of 10-5. Progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier method. Results: Among the 157 CAR-T pts, including 89 pts who received FDA-approved CAR-T, median age was 63 years, 59% (92/157) were males, 42% (66/157) had high risk cytogenetics with median of 5 prior lines of therapy, 36% (57/157) had plasmacytoma. Incidence of CRS was 83%, 5% grade ≥ 3 CRS. Incidence of ICANS was 19%, 4% grade ≥ 3 ICANS. CR/sCR rate was 37%. One hundred and thirty-seven pts (87%) had evaluable BM at month (mo) 1, 85% (117/137) were BM MRDneg at mo 1. Baseline demographics were comparable between the two groups except age, % BM plasma cells and use of bridging therapy. Among the MRDneg pts, CR/sCR rate was 44% (51/117) and 95% (111/117) had sFLC below normal. At median follow-up of 13.8 months, median PFS among pts with BM MRDneg at 1 mo was 12 mo (95% CI: 11, 30) vs 3 mo (95%CI: 2, 7) for BM MRDpos (p<0.001). Median OS among pts with BM MRDneg at 1 mo was 34 mo (95% CI: 24, NR) vs 22 mo (95%CI: 7, NA) for BM MRDpos (p<0.01). At month 1, 112 pts had both BM and PET/CT assessments available, 64/112(57%) were both BM MRDneg/PET MRDneg, 38/112 (34%) were MRDneg for either BM or PET and 10/112 (9%) were positive for both BM and PET (MRDpos/PET MRDpos). Baseline demographics except age were comparable between the 2 groups (Table). Rate of conversion from MRDpos to MRDneg was low. Rate of sustained BM and PET MRDneg at mo 12 was 44% (8/18). The median PFS and OS for BM MRDneg/PET MRDneg was significantly longer as compared to others (Table). Conclusions: Achieving FLC below normal, BM MRDneg and PET MRDneg at 1 month, regardless of IMWG response at that time, is prognostic for both PFS and OS in MM pts receiving CAR-T. Failure to achieve any of these confers poor prognosis. [Table: see text]

8012 Background: Cilta-cel was FDA approved in 2022 for the treatment of RRMM. We evaluated the outcomes of patients treated with intended SOC cilta-cel. Methods: 12 US academic medical centers contributed data to this retrospective study. As of 12/31/2022, 177 patients were leukapheresed and 139 received cilta-cel. Results: The table describes the study population compared to the CARTITUDE-1 trial. More patients in our study had extramedullary disease (EMD, 35%) and high-risk cytogenetics (41%). 55% of the patients would not have met eligibility criteria for CARTITUDE-1. Common reasons for ineligibility were cytopenias (19%), prior BCMA therapy (14%), organ dysfunction (12%), oligosecretory disease (13%), and plasma cell leukemia (8%). 83% of the patients received bridging chemotherapy (overall response rate, ORR: 28%). Lymphodepletion included fludarabine (Flu) + cyclophosphamide (Cy): 81%, bendamustine: 11%, Cy: 4%, and cladribine + Cy: 4%. Median CAR-T cells infused were 0.6 million/kg (range: 0.1-0.9), and 19% of patients were treated on an expanded access protocol (EAP). Median follow-up was 2.3 months (range: 0-8). Cytokine release syndrome (CRS) was seen in 81% (≥ grade 3: 7%) and immune effector cell-associated neurotoxicity syndrome (ICANS) in 22% (≥ grade 3: 8%) of patients. Tocilizumab, steroids, and anakinra were used in 61%, 44%, and 10% of patients, respectively. Delayed neurotoxicity (NT) was seen in 9% (cranial nerve palsy: 8, Parkinsonism: 2, others: 3). Grade ≥ 3 cytopenias at day ≥ 30 were seen in 75% of patients. Infections were seen in 32% of patients. Day 30 (N=115) and best response rates (N=118) were: ≥ partial response (PR), 75/80%; ≥ very good PR, 44/62%; and ≥ complete response (CR), 26/40%, respectively. In the non-EAP FluCy population (N=88), best ORR/≥CR were 89/49%. 17 patients died by data cut-off, 4 due to disease progression and 13 (9%) due to non-relapse mortality (NRM) (grade 5 CRS: 3, infection: 6, CRS/infection: 1, grade 5 ICANS: 1, delayed NT: 2). Conclusions: Patients treated with intended SOC cilta-cel had a favorable ORR (80%) despite a larger proportion of patients having high-risk features relative to trial patients and limited follow-up. Response rates were higher in patients receiving conforming products with FluCy conditioning (89%). Delayed NT and NRM were seen in 9% of patients. Results will be updated with continued follow-up. D.K.H., K.K.P, M.J., Y.L. & S.S. contributed equally. [Table: see text]

Abstract Introduction: The gut microbiome is a potentially modifiable factor in treatment related outcomes in allogeneic hematopoietic cell transplant (HCT). Prior studies have linked pre- or mid-treatment gut microbiome diversity with risk for treatment related morbidity and mortality. However, these studies have been limited by the inclusion of one or only a few institutions and the lack of longitudinal sampling with high quality metadata. These limitations complicate the interpretation of microbiome alterations over the course of HCT. Methods: To overcome these, we devised and implemented a large-scale biospecimen collection protocol in conjunction with BMT CTN 1703, a randomized, multicenter, Phase III trial of tacrolimus/methotrexate vs. post-transplant cyclophosphamide/tacrolimus/mycophenolate mofetil in reduced intensity conditioning (RIC) allogeneic HCT (NCT03959241). Patients enrolled on 1703 were optionally co-enrolled in the companion immune and microbiome profiling study, 1801 (MI-IMMUNE). This involved blood, urine and stool sampling before conditioning (PCON), then weekly starting on day 0 through day 77 (through day 84 for blood), and on days 98, 180, 270, 365 and 730. For all enrolled participants where the donor consented, residual donor cells were saved from the empty hematopoietic stem cell product bag for later analysis. Additionally, the protocol included one-time blood, urine and stool sample collection from consented matched related donors (MRDs) prior to stem cell collection. Starting with protocol version 4.0 on February 1, 2021, participation in 1801 stool collection was required for the first six out of eighteen sample collection timepoints. Participation in later stool and urine timepoint collections remained optional. Here we review the feasibility of creating a multi-institutional biobank. Additionally, we assess the success of our strategies by calculating sample collection compliance and standard deviation in compliance across centers for each timepoint. Results: On June 18, 2021, BMT CTN 1703/1801 closed to accrual with 431 patients enrolled on 1703; 323 patients from 36 centers were co-enrolled on 1801. 304 (94%) provided study samples, making this the largest prospective microbiome and immune profiling study in HCT patients to date. As of July 6, 2021, 3,683 blood, 2,668 urine, and 2,098 stool samples had been collected. Across the first 6 timepoints for all participating centers, blood, urine and stool sample collection averaged 93%, 82%, and 74% compliance, respectively. Of the 99 (30%) patients enrolled on 1801 with a MRD, 34 (34%) donors consented to sample collection. Sample collection compliance was lower for MRDs than for patients on the study with 76%, 74%, and 62% of expected blood, urine and stool samples collected, respectively, from this group. For stool collection exclusively, a median of 5 samples were collected per patient across the first 6 timepoints (median of 6 across all timepoints) with 93 (31%) of patients completing a full sample set through Day 28. 139 (46%) patients provided at least one sample after day 28; these represented 37% of the total samples collected to date. The PCON sample, which provides an important measure of pre-treatment gut microbiome diversity, had the third highest compliance with 74% of patients providing a sample. Surprisingly, Day 28 had the lowest compliance (66%) and highest standard deviation (37%) possibly because this timepoint often falls around the time of hospital discharge. Between PCON and day 28, the standard deviation between sites in the average collection compliance (24%) and number of samples collected per patient (1.1) was small indicating the successful adoption of stool collection across institutions. Table 1 summarizes sample collection statistics. Conclusion: Overall this study has resulted in a large, novel biobank of blood, urine and stool samples from patients undergoing RIC allogeneic HCT at 36 centers across the US. This will serve as a valuable resource for investigating the role of the gut microbiome in long term health outcomes following HCT. Although the results of 1801 are forthcoming given ongoing sample collection, the size and composition of the biobank to date clearly demonstrate the feasibility of implementing multi-institutional stool collection. This study represents a critical step towards the large-scale adoption of microbiome sampling as a diagnostic tool. Figure 1 Figure 1. Disclosures Chhabra: GSK: Honoraria. Clark: Kadmon: Consultancy. Horowitz: Mesoblast: Research Funding; Shire: Research Funding; Vertex: Research Funding; Stemcyte: Research Funding; Vor Biopharma: Research Funding; Janssen: Research Funding; Miltenyi Biotech: Research Funding; Kiadis: Research Funding; Sobi: Research Funding; Kite/Gilead: Research Funding; Pfizer, Inc: Research Funding; Jazz Pharmaceuticals: Research Funding; Magenta: Consultancy, Research Funding; Medac: Research Funding; Novartis: Research Funding; GlaxoSmithKline: Research Funding; Daiicho Sankyo: Research Funding; Xenikos: Research Funding; Omeros: Research Funding; Orca Biosystems: Research Funding; Pharmacyclics: Research Funding; Regeneron: Research Funding; Tscan: Research Funding; Takeda: Research Funding; CSL Behring: Research Funding; Genentech: Research Funding; Gamida Cell: Research Funding; Chimerix: Research Funding; Bristol-Myers Squibb: Research Funding; bluebird bio: Research Funding; Astellas: Research Funding; Amgen: Research Funding; Allovir: Consultancy; Actinium: Research Funding; Sanofi: Research Funding; Seattle Genetics: Research Funding. Jenq: Microbiome DX: Consultancy; Merck: Consultancy; Prolacta: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kaleido: Consultancy, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seres: Consultancy, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; LisCure: Consultancy, Membership on an entity's Board of Directors or advisory committees; MaaT Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karius: Consultancy. Levine: Equillium Bio: Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Research Funding; Kamada: Research Funding; Biogen: Research Funding; Omeros: Membership on an entity's Board of Directors or advisory committees; Symbio: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Talaris Therapeutics: Membership on an entity's Board of Directors or advisory committees; Viracor: Patents & Royalties: GVHD biomarker patent with royalties from Viracor; Mesoblast: Consultancy, Research Funding; X4 Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Murthy: CRISPR Therapeutics: Research Funding. Riches: ATARA Biotherapeutics: Other: Payment; BioIntelect: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Other: Payment. Sung: Merck: Research Funding; Novartis: Research Funding; Enterome: Research Funding; Seres: Research Funding; AVROBIO: Consultancy; Abbott Nutrition: Honoraria; Clasado: Other: Research Product; DSM: Other: Research Product. Al Malki: Neximmune: Consultancy; Jazz Pharmaceuticals, Inc.: Consultancy; Rigel Pharma: Consultancy; Hansa Biopharma: Consultancy; CareDx: Consultancy. Rezvani: Kaleido: Other: One-time scientific advisory board; Nohla Therapeutics: Other: One-time scientific advisory board; Pharmacyclics-Abbvie: Research Funding; US Department of Justice: Consultancy. Bolaños-Meade: Incyte Corp: Consultancy. Holtan: Incyte: Consultancy, Research Funding; Generon: Consultancy. Saber: Govt. COI: Other. Hamadani: Sanofi, Genzyme, AstraZeneca, BeiGene: Speakers Bureau; Janssen, Incyte, ADC Therapeutics, Omeros, Morphosys, Kite: Consultancy; Takeda, Spectrum Pharmaceuticals and Astellas Pharma: Research Funding. Kean: Bluebird Bio: Research Funding; Bristol Myers Squibb: Patents & Royalties: From clinical trial data, Research Funding; Vertex: Consultancy; Novartis: Consultancy; Gilead: Research Funding; Regeneron: Research Funding; EMD Serono: Consultancy. Perales: Cidara: Honoraria; Servier: Honoraria; Incyte: Honoraria, Other; Equilium: Honoraria; Takeda: Honoraria; Novartis: Honoraria, Other; Nektar Therapeutics: Honoraria, Other; NexImmune: Honoraria; MorphoSys: Honoraria; Omeros: Honoraria; Karyopharm: Honoraria; Sellas Life Sciences: Honoraria; Merck: Honoraria; Miltenyi Biotec: Honoraria, Other; Medigene: Honoraria; Bristol-Myers Squibb: Honoraria; Kite/Gilead: Honoraria, Other; Celgene: Honoraria.

Abstract Background Allogeneic (off the shelf) chimeric antigen receptor (CAR) T-cell therapy addresses the logistical challenges, availability (including insufficient T-cell yields from low baseline absolute lymphocyte count), and variable product quality of autologous CAR T therapy. ALLO-715 is a genetically modified anti-BCMA AlloCAR T™ cell which uses Cellectis TALEN ® technology to disrupt the T-cell receptor alpha constant gene (TRAC) and the CD52 gene to reduce the risk of graft-versus-host disease (GvHD) and permit the use of ALLO-647, an anti-CD52 monoclonal antibody (mAb), for selective and transitory host lymphodepletion (LD). Methods UNIVERSAL is an open-label, Phase 1 trial (NCT04093596) in adults with relapsed/refractory (R/R) multiple myeloma who have received ≥3 prior lines of therapy including a proteasome inhibitor, immunomodulator, and anti-CD38 mAb. Patients (pts) must be refractory to their last treatment line. Pts receive LD followed by ALLO-715 at 1 of 4 dose levels (DLs) in a 3+3 dose escalation design: 40, 160, 320, and 480 x 10 6 CAR+ T cells. Several LD regimens are being evaluated: FCA39; FCA60; FCA90; and CA39; with fludarabine [F] 90 mg/m 2, cyclophosphamide [C] 900 mg/m 2, and ALLO-647 [A] 39, 60, or 90 mg divided over 3 days. Results As of June 21, 2021 data-cut, 47 subjects were enrolled; 42 were treated with ALLO-715; 5 progressed prior to treatment. Median time from enrollment to LD was 5 days and no treated pts required bridging therapy. Pts were heavily pretreated with a range of 3-11 prior lines of therapy; 42.9% were penta refractory. There were 19% ISS Stage III at screening, 34% had high risk cytogenetics, and 19% had extramedullary disease. The most common Grade (Gr) 3+ adverse events (AEs) included anemia, neutropenia, lymphopenia, and thrombocytopenia. Cytokine release syndrome (CRS) occurred in 52.4%, all Gr 1/2 except 1 pt with Gr 3. CRS was treated with tocilizumab (21.3%) and corticosteroids (12.8%). One pt (with Gr 2 CRS) experienced Gr 1 neurotoxicity that resolved. Gr 3+ infections occurred in 12.8% of pts, including 2 previously reported Gr 5 events (fungal pneumonia and adenovirus hepatitis). Early results from this trial have been presented previously (ASH 2020) and therefore the efficacy analysis on pts (n=26) treated at DL3 and DL4 with FCA LD, which are considered a more relevant cell dose and LD, is presented here (Table). In pts who received DL3 or DL4 (320 or 480 x 10 6 CAR T cells) (n=26), the ORR was 61.5% (95% CI: 40.6, 79.8); very good partial response or better (VGPR+) rate was 38.5% (95% CI: 20.2, 59.4). Median time to 1 st response was 16 days. The median follow-up for the DL3/DL4 pts was 7.4 months (95% CI: 3.6, 9.9) with a median duration of response of 8.3 months (95% CI: 1.5, not reached). Of the 10 pts with a best response of VGPR+, 8 were found to be negative by minimal residual disease (MRD) analysis. Conclusions UNIVERSAL demonstrates proof of concept for allogeneic CAR T therapy in multiple myeloma. ALLO-715 showed CAR T cell dose response relationship with higher doses (DL3/DL4) leading to clinically meaningful efficacy, including high VGPR+ rate of 38.5% and high MRD negativity without requiring leukapheresis or bridging therapy. ALLO-715 following LD with FCA has a tolerable safety profile. FCA induces a deep and durable window of lymphocyte depletion allowing CAR T cell expansion and persistence. A study using the next generation anti-BCMA CAR (ALLO-605) which supplies cytokine signaling to the CAR bearing cells is ongoing (IGNITE). The current UNIVERSAL trial continues to enroll, including a cohort with consolidation, and updated data will be presented at the meeting. Figure 1 Figure 1. Disclosures Mailankody: Allogene Therapeutics: Research Funding; Plexus Communications: Honoraria; Fate Therapeutics: Research Funding; Physician Education Resource: Honoraria; Bristol Myers Squibb/Juno: Research Funding; Jansen Oncology: Research Funding; Legend Biotech: Consultancy; Evicore: Consultancy; Takeda Oncology: Research Funding. Liedtke: Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; Kura Oncology: Membership on an entity's Board of Directors or advisory committees; Alnylam: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Caelum: Membership on an entity's Board of Directors or advisory committees, Other: Clinical Trial Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Sidana: BMS: Consultancy; Magenta Therapeutics: Consultancy, Research Funding; Allogene: Research Funding; Janssen: Consultancy, Research Funding. Chhabra: GSK: Honoraria. Oluwole: Janssen: Consultancy; Pfizer: Consultancy; Curio Science: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding. Kumar: Oncopeptides: Consultancy; Antengene: Consultancy, Honoraria; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bluebird Bio: Consultancy; Roche-Genentech: Consultancy, Research Funding; Merck: Research Funding; Carsgen: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Research Funding; Beigene: Consultancy; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Tenebio: Research Funding; Sanofi: Research Funding. Nath: Actinium: Consultancy, Honoraria; Incyte: Consultancy, Honoraria. Anwer: Janssen pharmaceutical: Honoraria, Research Funding; Allogene Therapeutics: Research Funding; GlaxoSmithKline: Research Funding; BMS / Celgene: Honoraria, Research Funding. Raje: Caribou: Other; Janssen: Other; bluebird bio: Other; Amgen: Other; Celgene: Other; BMS: Other. Siegel: Bristol Myers Squibb: Honoraria, Speakers Bureau; Takeda: Honoraria; GlaxoSmithKline: Honoraria, Speakers Bureau; Celularity: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Honoraria; Amgen Inc.: Honoraria; Janssen: Honoraria, Speakers Bureau. Karski: Allogene Therapeutics: Current Employment, Current equity holder in publicly-traded company; Crispr Therapeutics: Current equity holder in publicly-traded company; Nektar Therapeutics: Current equity holder in publicly-traded company. Lovelace: Allogene Therapeutics, Inc.: Current Employment. Lourbakos: Allogene Therapeutics, Inc.: Current Employment. Hari: Millenium: Membership on an entity's Board of Directors or advisory committees, Research Funding; 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; Adaptive Biotech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; 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; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau; Karyopharm: Consultancy; 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.

Abstract Background: MM that is refractory to a proteasome inhibitor (PI), an immunomodulatory agent (IMiD) and an anti-CD38 monoclonal antibody (CD38MoAb) is labeled triple-class refractory (TCR) and recognized as a modern therapeutic challenge. In recent years, new agents have shown activity in this setting in single arm trials and many more are in development. The assessment of the impact of new agents in the TCR setting is impaired by limited information on the therapeutic outcomes of these patients when treated with non-investigational therapies. Methods: We utilized an independent RWD dataset of patients with MM refractory to CD38MoAb built from academic collaboration (MAMMOTH study) to identify patients with TCR MM who received subsequent therapy. Patients with MM that was CD38MoAb refractory but not TCR were followed longitudinally and only included if, after subsequent lines of therapy, MM became TCR. Patients were excluded if they had plasma cell leukemia, poor renal function (serum creatinine &gt; 2 mg/dl) or if next therapy after TCR status included experimental agents. Refractoriness to a MM agent was defined as lack of objective response and/or progression while receiving therapy or within 60 days of last dose as per International Myeloma Working Group (IMWG) criteria. Time zero for analysis was initiation of next therapy after MM became TCR. Response to therapy and progression were adjudicated utilizing IMWG criteria. MM that was TCR but also exposed to 2 PIs, 2 IMiDs and a CD38MoAb was considered penta-exposed, and when refractory to 2 PIs, 2 IMiDs and a CD38MoAb, it was considered penta-refractory. Results: Data collection occurred between 2016 and 2018 (prior to commercial availability of selinexor, belantamab mafodotin, melflufen or ide-cel). Of 275 patients in the MAMMOTH study, 177 were included. Median age was 65 years (range 27-90), 53% were male, 76% white, 28 % had International Staging System stage 3, and 29% high risk cytogenetics [t(4;14), t(14;16) or del(17p)]. Median number of prior lines of therapy was 5 (range 3-17), median time from diagnosis to TCR was 4.8 years (range 0.9-19.4), 73% had received prior autologous hematopoietic cell transplantation, 84% were refractory to bortezomib or ixazomib, 58% were refractory to carfilzomib, 87% to lenalidomide and 74% to pomalidomide. Penta-exposed patients were 58% and penta-refractory 30%. The first regimen after MM became TCR included cytotoxic chemotherapy in 45%, CD38MoAb in 25%, SLAMF7 MoAb in 7%, carfilzomib in 24%, and pomalidomide in 34% of cases. Overall response rate (ORR) was 30% (20.9% PR, 7.3% VGPR and 1.7% CR). Median progression-free survival (PFS) was 2.8 mo. (95% C.I. 2.3-3.2) and overall survival (OS) 8.6 mo. (95% C.I. 6.8-10.3),(Figure). For Patients with MM that was penta-exposed (N=102), ORR was 30%, median PFS was 2.7 mo (95% C.I 2.1-3.2), and median OS 7.7 mo (95% C.I. 6.0-9.4). For patients with penta-refractory MM (N=53), ORR was 32%, median PFS was 2.5 mo. (95% C.I. 1.7-3.3), and median OS 6.9 mo. (95% C.I. 4.9-8.9). PFS or OS was similar among patients who were TCR but not penta-exposed, TCR plus penta-exposed but not penta- refractory or TCR plus penta-refractory (Figure). Outcomes according to next regimen after MM became TCR are outlined in the Table. In multivariable analysis, no factor was predictor of PFS while refractoriness to carfilzomib (HR 2.2, 95% C.I. 1.5-3.3), presence of high-risk chromosome abnormalities (HR 1.5, 95% C.I. 1.0-2.2) and short interval from diagnosis to TCR (HR 0.92, 95% C.I. 0.85-0.99) were predictors of shorter OS. Conclusions: Patients with TCR MM have a uniformly low chance of response to subsequent conventional therapy with short PFS and OS even when not penta-exposed or penta-refractory. This dataset provides efficacy benchmark for new therapies being developed in this setting. Figure 1 Figure 1. Disclosures Costa: BMS: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau. Cornell: Abvvie: Current Employment. Chhabra: GSK: Honoraria. Liedtke: Janssen Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Caelum: Membership on an entity's Board of Directors or advisory committees, Other: Clinical Trial Funding; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; Kura Oncology: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Alnylam: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Kansagra: GSK: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Cota Health: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Alynylam: Membership on an entity's Board of Directors or advisory committees. Giri: PackHealth: Research Funding; CareVive: Honoraria, Research Funding. Malek: Amgen: Honoraria; Janssen: Other: Advisory board ; Cumberland Inc.: Research Funding; Bluespark Inc.: Research Funding; BMS: Honoraria, Research Funding; Sanofi: Other: Advisory Board; Medpacto Inc.: Research Funding; Takeda: Honoraria. Vij: BMS: Research Funding; Takeda: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; BMS: Honoraria; GSK: Honoraria; Oncopeptides: Honoraria; Karyopharm: Honoraria; CareDx: Honoraria; Legend: Honoraria; Biegene: Honoraria; Adaptive: Honoraria; Harpoon: Honoraria. Usmani: Celgene/BMS: Consultancy, Research Funding, Speakers Bureau; Array BioPharma: Consultancy, Research Funding; Amgen: Consultancy, Research Funding, Speakers Bureau; Abbvie: Consultancy; EdoPharma: Consultancy; GSK: Consultancy, Research Funding; Janssen: Consultancy, Research Funding, Speakers Bureau; Sanofi: Consultancy, Research Funding, Speakers Bureau; Merck: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; SkylineDX: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Takeda: Consultancy, Research Funding, Speakers Bureau; Janssen Oncology: Consultancy, Research Funding; Bristol-Myers Squibb: Research Funding. Hari: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, 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; 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; 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; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau; Karyopharm: Consultancy; Celgene-BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau. Kumar: Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Carsgen: Research Funding; Novartis: Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche-Genentech: Consultancy, Research Funding; Bluebird Bio: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Tenebio: Research Funding; Antengene: Consultancy, Honoraria; Beigene: Consultancy; Oncopeptides: Consultancy; Sanofi: Research Funding.

Abstract Little is known about whether risk classification at diagnosis predicts post-hematopoietic cell transplantation (HCT) outcomes in patients with acute myeloid leukemia (AML). We evaluated 8709 patients with AML from the CIBMTR database, and after selection and manual curation of the cytogenetics data, 3779 patients in first complete remission were included in the final analysis: 2384 with intermediate-risk, 969 with adverse-risk, and 426 with KMT2A-rearranged disease. An adjusted multivariable analysis detected an increased risk of relapse for patients with KMT2A-rearranged or adverse-risk AML as compared to those with intermediate-risk disease (hazards ratio [HR], 1.27; P = .01; HR, 1.71; P &lt; .001, respectively). Leukemia-free survival was similar for patients with KMT2A rearrangement or adverse risk (HR, 1.26; P = .002, and HR, 1.47; P &lt; .001), as was overall survival (HR, 1.32; P &lt; .001, and HR, 1.45; P &lt; .001). No differences in outcome were detected when patients were stratified by KMT2A fusion partner. This study is the largest conducted to date on post-HCT outcomes in AML, with manually curated cytogenetics used for risk stratification. Our work demonstrates that risk classification at diagnosis remains predictive of post-HCT outcomes in AML. It also highlights the critical need to develop novel treatment strategies for patients with KMT2A-rearranged and adverse-risk disease.

Abstract The role of haploidentical hematopoietic cell transplantation (HCT) using posttransplant cyclophosphamide (PTCy) for acute lymphoblastic leukemia (ALL) is being defined. We performed a retrospective, multivariable analysis comparing outcomes of HCT approaches by donor for adults with ALL in remission. The primary objective was to compare overall survival (OS) among haploidentical HCTs using PTCy and HLA-matched sibling donor (MSD), 8/8 HLA-matched unrelated donor (MUD), 7 /8 HLA-MUD, or umbilical cord blood (UCB) HCT. Comparing haploidentical HCT to MSD HCT, we found that OS, leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and acute graft-versus-host disease (aGVHD) were not different but chronic GVHD (cGVHD) was higher in MSD HCT. Compared with MUD HCT, OS, LFS, and relapse were not different, but MUD HCT had increased NRM (hazard ratio [HR], 1.42; P = .02), grade 3 to 4 aGVHD (HR, 1.59; P = .005), and cGVHD. Compared with 7/8 UD HCT, LFS and relapse were not different, but 7/8 UD HCT had worse OS (HR, 1.38; P = .01) and increased NRM (HR, 2.13; P ≤ .001), grade 3 to 4 aGVHD (HR, 1.86; P = .003), and cGVHD (HR, 1.72; P ≤ .001). Compared with UCB HCT, late OS, late LFS, relapse, and cGVHD were not different but UCB HCT had worse early OS (≤18 months; HR, 1.93; P &lt; .001), worse early LFS (HR, 1.40; P = .007) and increased incidences of NRM (HR, 2.08; P &lt; .001) and grade 3 to 4 aGVHD (HR, 1.97; P &lt; .001). Haploidentical HCT using PTCy showed no difference in survival but less GVHD compared with traditional MSD and MUD HCT and is the preferred alternative donor HCT option for adults with ALL in complete remission.

8030 Background: CARTITUDE-1 is a single arm study of Ciltacabtagene autoleucel (cilta-cel; JNJ-68284528) anti-BCMA CAR-T cell therapy in US patients (pts) with relapsed multiple myeloma (RRMM) refractory to both IMiD and proteasome inhibitor (PI) or with at least 3 prior lines of therapy and previously exposed to anti-CD38 monoclonal antibody (MoAb). While recently reported efficacy results of cilta-cel were encouraging, it is unknown how they compare with similar pts receiving conventional (non CAR-T) treatment. Methods: We utilized a contemporary US-based dataset of pts with MM refractory to anti-CD38 MoAb (MAMMOTH) to identify pts who would meet eligibility for CARTITUDE-1 and who received conventional therapy. We analyzed the intent-to-treat population (ITT) in CARTITUDE-1, defined as pts who underwent apheresis (N=113) and a modified ITT population (mITT) defined as subset of pts who received cilta-cel at the RP2D (N=97). From the MAMMOTH dataset, we identified a population corresponding to CARTITUDE-1 ITT (N=190) and a mITT population, pts without death or progression within 47 days (median time between apheresis and cilta-cel infusion) from onset of therapy (N=122). We calculated propensity scores (PS) with demographics, N of prior therapies, cytogenetics and refractoriness to MM agents as covariates. An analyst blinded to outcomes performed nearest neighbor 1:1 PS matching. We analyzed overall response rate (ORR), progression-free (PFS) and overall survival (OS) for ITT and mITT in CARTITUDE-1 vs matching MAMMOTH cohorts. Results: Ninety-five ITT (75 received bridging therapy, 82 received cilta-cel) and 69 mITT (54 received bridging) CARTITUDE-1 pts matched MAMMOTH pts (Table). Among the pts in the MAMMOTH ITT cohort 34% received pomalidomide, 24% anti-CD38 MoAb, 19% carfilzomib and 35% cytotoxic chemotherapy in next therapy. ORR in the ITT cohorts was higher in CARTITUDE-1 (84% vs. 28%). Compared to their MAMMOTH counterparts, pts in CARTITUDE-1 ITT cohort had improved PFS (12 mo. 73% vs. 12%) and OS (12 mo. 83% vs 39%). Between the mITT cohorts, CARTITUDE-1 pts had superior ORR (96% vs. 30%), PFS (12 mo 79% vs. 15%) and OS (12 mo. 88% vs. 41%). Conclusions: In pts with RRMM beyond therapy with IMID, PI, and anti-CD38 MoAb, treatment with cilta-cel is associated with higher response rate and superior PFS and OS when compared to conventional treatment.[Table: see text]