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Kroog, Glenn S.

https://orcid.org/0009-0000-2897-9810

Mayo Clinic

Regeneron (United States)

Citations 15

Real-world outcomes and subsequent treatment utilization following anti-B-cell maturation antigen antibody-drug conjugate exposure in patients with multiple myeloma.
Dimopoulos, M A, Urrea, Jorge Monge, Kastritis, E K, Leleu, Xavier P., Siegel, David Samuel DiCapua, Ocio, Enrique M., Nagaraj, Madhu , Hassan, Rafla , Jagannath, Sundar, Weisel, K, Bonar, Nicolle , Green, Jeannette, Kroog, Glenn S. , Ma, Qiufei, Kumar, Shaji, Leleu, Xavier , Ocio, Enrique M. , Jagannath, Sundar , Weisel, Katja C , Shokoohi, Mostafa , Hampp, Christian , Humblet, Olivier , Breskin, Alexander , Ma, Qiufei , Kumar, Shaji

Journal of Clinical Oncology | May 28, 2026 | Volume: 44 | Issue: 16_suppl | Pages: No page available

10.1200/jco.2026.44.16_suppl.e19503 Get It

e19503 Background: The anti-B-cell maturation antigen (BCMA) antibody-drug conjugate (ADC) belantamab mafodotin is approved in the USA and EU for relapsed/refractory multiple myeloma (RRMM). Understanding treatment options and patient outcomes following ADC failure is clinically important. This study describes post-ADC treatment patterns and clinical outcomes in real-world patients with RRMM. Methods: Adult patients with MM who received an ADC and initiated ≥1 subsequent line of therapy (LOT) were included. The index date was the start of the first post-ADC LOT. Data were obtained from chart reviews at International Myeloma Foundation International Myeloma Working Group (IMF IMWG) academic sites, and US electronic health records from largely community sites (COTA and Guardian Research Network [GRN]). Patient characteristics and index regimens were summarized descriptively. Time to next treatment (TTNT) and overall survival (OS) were estimated with the Kaplan-Meier estimator. Results: The IMF IMWG cohort (n=40) had a mean age of 70.8 years, median of 7 prior LOTs and 82.5% were triple-class refractory (TCR). Overall, 85% received ADC monotherapy (70% belantamab mafodotin) and 15% combination therapy. Pre-ADC and not considering corticosteroids, patients were commonly exposed to lenalidomide (R; 100%), bortezomib (V; 92.5%), daratumumab (D) and pomalidomide (P; 90% each). Over a median follow-up of 26 months after index date, 29 unique index post-ADC regimens were reported, frequently selinexor (27.5%) and bispecific antibodies (15%). CAR T-cell therapy was administered to 5%, with 60% re-treated with a pre-ADC drug class (PI/IMiD/anti-CD38) after ADC. Median (95% CI) TTNT and OS were 10.8 (7.0–20.6) and 19.0 (13.4–25.1) months, respectively. The COTA-GRN cohort (n=39) had a mean age of 67.5 years, median of 8 prior LOTs, and 51.3% were TCR. Overall, 56% received ADC monotherapy (belantamab mafodotin) and 44% combination therapy. Pre-ADC and not considering corticosteroids, patients were commonly exposed to D and R (97.4% each), and carfilzomib, V and P (94.9% each). Over a median follow-up of 9.2 months, 32 unique index post-ADC regimens were reported, frequently selinexor (23.1%) and venetoclax (17.9%) based; 0% received CAR Ts and 54% were re-treated with a pre-ADC drug class (PI/IMiD/anti-CD38) after ADC. Median (95% CI) TTNT and OS were 4.9 (2.8–non-estimable [NE]) and 12.0 (4.9–NE) months, respectively. Conclusions: Findings highlight that most patients with heavily pretreated BCMA-ADC exposed MM were re-treated with similar classes. Academic centers used novel therapies (ie, CAR T, bispecific antibodies) more often and their patients had longer survival than those treated at community sites. However, clinical outcomes remained sub-optimal, emphasizing the unmet need for effective, accessible post-ADC treatments.
Safety and efficacy of linvoseltamab (LINVO) combined with anti-CD38 monoclonal antibodies (mAbs) daratumumab (DARA) or isatuximab (ISA) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): Initial results from the multicohort, Phase 1b LINK
Manier, Salomon, Rubinstein, Samuel M. , Chamorro, Maria Del Carmen Martinez, Breazna, Aurora, Dhadwal, Amishi, Masinde, Sheila , Kroog, Glenn S. , Sarkaria, Shawn , Dimopoulos, Meletios Α. , Delimpasi, Sosana , Manier, Salomon, Michot, Jean‐Marie , Ocio, Enrique M. , Cook, Joselle , Ghodke‐Puranik, Yogita , Oriol, Albert

Blood | December 4, 2025 | Volume: 146 | Issue: Supplement 1 | Pages: 2254-2254

10.1182/blood-2025-2254 Get It

Abstract Introduction LINVO, a human B-cell maturation antigen (BCMA)xCD3 bispecific antibody, was recently approved for triple-class exposed (TCE) RRMM after ≥3 prior therapies (EU) or ≥4 prior lines of therapy (US), demonstrating high efficacy and a generally manageable safety profile. Combining LINVO with an anti-CD38 mAb, such as DARA or ISA, may provide additional benefit to pts with RRMM. Here we report pooled safety and efficacy results from the LINVO + DARA and LINVO + ISA cohorts during the dose-finding portion of the Phase 1b LINKER-MM2 trial (NCT05137054). Methods Eligible pts were aged ≥18 years with RRMM that progressed after ≥3 lines of therapy (LoTs), or ≥2 LoTs if TCE or double-class refractory (immunomodulatory drug [IMiD] + proteasome inhibitor [PI]). Prior treatment (tx) with DARA or ISA was allowed if previously tolerated and ≥6 months (mos) or ≥3 mos washout, respectively, had elapsed since last exposure. Tx began with LINVO monotherapy (Cycle [C]0; 28-day cycle) consisting of 2 step-up doses (5 mg, 25 mg) and 2 full doses (dose level [DL]1 100 mg; DL1b 150 mg; DL2 200 mg) before standard dosing of DARA or ISA was added at C1. LINVO was given once weekly in C1–3 and once every 2 weeks in C4+. At the end of 2024, dosing once every 4 weeks was implemented after C6 if a very good partial response or better (≥VGPR) was achieved. Dexamethasone premedication was required during the first 2 cycles and then given per label for DARA or ISA. Primary endpoints: dose-limiting toxicities (DLTs) and tx-emergent adverse events (TEAEs). Key secondary endpoints: overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and rate of minimal residual disease (MRD) negativity. The analyses reported here combine the LINVO + DARA and LINVO + ISA cohorts. Results As of May 7, 2025, 42 pts were enrolled. All pts were included in the safety analysis set: DL1 (DARA, n=12; ISA, n=6), DL1b (n=6; n=10), or DL2 (n=8; n=0); 37 were included in the efficacy analysis set: DL1 (DARA, n=11; ISA, n=5), DL1b (n=5; n=9), or DL2 (n=7; n=0). At baseline, all pts had received ≥1 PI (refractory to ≥1 PI: 76%) or ≥1 IMiD (refractory to ≥1 IMiD: 86%), and 21 pts (50%) had received prior DARA or ISA (refractory to DARA or ISA: 33% [DARA, n=4; ISA, n=10]). Median number of prior LoTs was 3 (range 2–8), including 50% of pts with TCE and 21% with triple-class refractory disease. Median age was 68 years (range 42–86); male, 57%; ISS stage III at study entry, 12%; high-risk cytogenetics, 31%; bone marrow plasma cells ≥50%, 31%; and soft tissue plasmacytomas, 33% (extramedullary, 12%). Median follow-up duration was 14.8 mos for DL1 (DARA 21.3; ISA 11.3), 7.6 mos for DL1b (DARA 13.5; ISA 5.2), and 5.9 mos for DL2 (all DARA), with 44%, 50%, and 63% of pts still receiving tx, respectively. The most common TEAEs were anemia (any grade [Gr] 48%; Gr 3/4 26%), neutropenia (41%; 41%), diarrhea (38%; 2%), and thrombocytopenia (38%; 17%). Cytokine release syndrome was reported in 33% of pts (all Gr 1/2 events except 1 Gr 3 event during the step-up period that fully resolved). No pts experienced immune effector cell-associated neurotoxicity syndrome (ICANS). Infections were reported in 32 pts (any Gr 76%; Gr ≥3 40%), and 3 resulted in death (1 tx related: cytomegalovirus [CMV] pneumonia; 2 tx unrelated: C. diff colitis and lower respiratory infection). One DLT was observed at DL1b in the ISA cohort (Gr 3 Epstein–Barr virus pharyngitis) and 1 was observed at DL2 in the DARA cohort (Gr 5 CMV pneumonia). Among efficacy evaluable pts, ORR was 75% at DL1 (12/16; ≥VGPR rate 75%), 93% at DL1b (13/14; ≥VGPR rate 57%), and 86% at DL2 (6/7; ≥VGPR rate 86%). Of 10 MRD-evaluable pts, all were MRD negative (<10−5by clonoSEQ or EuroFlow). The 12-mo DOR rate was 79% (95% confidence interval [CI] 52–92; median DOR not reached) and 12-mo PFS rate was 73% (95% CI 53–86; median PFS not reached). Pharmacokinetic analyses showed LINVO concentrations were not affected by the addition of DARA or ISA. ConclusionsIn pts with heavily pretreated RRMM, half of whom had prior anti-CD38 mAb exposure, the combination of LINVO and DARA or ISA was feasible, inducing a high rate of deep and durable responses, and exhibiting a safety profile similar to that reported for each individual drug. These preliminary data support continued development of LINVO plus an anti-CD38 mAb for the tx of pts with MM.
A plain language summary of patient preferences for treatments for multiple myeloma that has relapsed or is refractory to prior therapy
Mansfield, Carol , Bussberg, Cooper , Chi, Lei, Kroog, Glenn S. , Rodriguez-Lorenc, Karen, Ahlstrom, Jenny, Ma, Qiufei , Ailawadhi, Sikander , Inocencio, Timothy J. , Chintakayala, Phani , Harnett, James

Future Oncology | December 1, 2025 | Volume: 21 | Issue: 29 | Pages: 3701-3711

10.1080/14796694.2025.2584284 Get It

Concordance between blinded independent central review committee and physician-assessed responses: Analyses based on a real-world external control arm in relapsed/refractory multiple myeloma using International Myeloma Working Group data.
Durie, Brian G.M. , Siddiqui, Muhaimen, Bonar, Nicolle , Spin, Paul , Green, Jeannette, Kroog, Glenn S. , Ma, Qiufei , Kumar, Shaji , Rosiñol, Laura , Weisel, Katja C , Jagannath, Sundar , Shokoohi, Mostafa , West, Michael, Hampp, Christian , Harnett, James , Humblet, Olivier , Breskin, Alexander

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: No page available

10.1200/jco.2025.43.16_suppl.e19521 Get It

e19521 Background: Blindedindependent central review (BICR) committees are often established for oncology trials to assessbestoverall response (BOR), while real-world (RW) studies typically rely on physician-assessed responses. To emulate clinical trial rigor, a BICR committee was implemented in the R5458-ONC-21101 RW data-derived external control arm study (NCT05673967) to evaluate BOR using International Myeloma Working Group (IMWG) criteria. A pre-specified concordance analysis compared BOR assessments between the BICR committee and treating site physicians. Methods: RW data were obtained from chart reviews at 15 participating International Myeloma Foundation IMWG sites. The BICR committee, comprised of three multiple myeloma experts, evaluated BOR through consensus voting. Per protocol, the committee reviewed case report forms consisting of data on serum and urine myeloma protein and free light chain levels; and, where available, bone marrow plasma cell percentage, presence of plasmacytomas, and bone lesion changes. Concordance between BICR- and physician-assessed BOR was evaluated for objective response rate defined as ≥partial response (PR), ≥very good partial response (VGPR), ≥complete response (CR), and stringent complete response (sCR), with non-evaluable responses excluded from the analysis. Cohen’s kappa (κ) was used to measure agreement, with values >0.6 indicating strong concordance. 1 Results: Of 279 evaluable lines of therapy from 203 patients (Table), the BOR of ≥PR was 45.2% by BICR assessment and 42.3% by treating physicians (κ=0.622). Concordance improved for BOR of ≥VGPR (22.2% by BICR vs 24.7% by treating physicians; κ=0.731) but was low for BOR of ≥CR (3.9% vs. 10.8%; κ=0.508) and sCR (1.1% vs. 4.7%; κ=0.364). Conclusions: BICR- and physician-assessed responses showed strong concordance for BOR of ≥PR and ≥VGPR. However, as expected, lower concordance for ≥CR and sCR was observed, as evaluation of CR per IMWG criteria requires a bone marrow biopsy, which is rarely performed in clinical practice. While the reliability of CR and sCR in RW data is less certain, these results suggest that BOR of ≥VGPR or ≥PR may be reliably ascertained in academic settings based on treating physician evaluations. 1. Landis JR, Koch GG. Biometrics 1977;33(1):159–74. Clinical trial information: NCT05673967 . Agreement of BICR- and physician-assessed responses. BICR assessed Physician assessed Observed agreement, % Cohen’s kappa* Number of evaluable lines of therapy 279 279 - - ≥PR, n (%) 126 (45.2) 118 (42.3) 81.4 0.622 ≥VGPR, n (%) 62 (22.2) 69 (24.7) 90.3 0.731 ≥CR, n (%) 11 (3.9) 30 (10.8) 93.2 0.508 sCR, n (%) 3 (1.1) 13 (4.7) 96.4 0.364 *A kappa value >0.6 indicates strong concordance. 1
Patient preferences for triple-class–exposed relapsed or refractory multiple myeloma treatment: a discrete-choice study
Inocencio, Timothy J. , Mansfield, Carol , Bussberg, Cooper , Chi, Lei, Kroog, Glenn S. , Rodriguez-Lorenc, Karen, Ma, Qiufei , Inocencio, Timothy J , Mansfield, Carol , Chintakayala, Phani , Harnett, James , Kroog, Glenn S , Ailawadhi, Sikander

Future Oncology | February 27, 2025 | Volume: 21 | Issue: 7 | Pages: 853-865

10.1080/14796694.2025.2461430 Get It

Comparative Effectiveness of Linvoseltamab Versus Current Real-World Standard of Care Therapies in Triple-Class Exposed Relapsed/Refractory Multiple Myeloma Treated at IMWG Sites
Kumar, Shaji , Dachs, Laura Rosiñol, Monge, Jorge, Leleu, Xavier , Rubia, Javier de la , Mateos, María-Victoria, Gozzetti, Alessandro , Bladé, Joan , Nagaraj, Madhu , Hassan, Rafla , Green, Jeannette, Kroog, Glenn S. , Lorenc, Karen Rodriguez , Ma, Qiufei , Durie, Brian G.M. , Gozzetti, Alessandro , Jagannath, Sundar , Weisel, Katja C , Dimopoulos, Meletios Α. , Siegel, David S. , Monge, Jorge , Du, Juan , Lee, Jae Hoon , Mateos, María‐Victoria , Dytfeld, Dominik , Ocio, Enrique M. , Ozaki, Shuji , Hampp, Christian

Blood | December 5, 2024 | Volume: 144 | Issue: Supplement 1 | Pages: 7039-7039

10.1182/blood-2024-210376 Get It

Introduction Multiple myeloma (MM) is considered incurable. Despite improved outcomes with novel agents, including BCMA-targeted chimeric antigen receptor (CAR) T-cell therapies, antibody-drug conjugates (ADCs), and bispecific antibodies, patients with relapsed/refractory MM (RRMM) often have poor prognoses. LINKER-MM1 (NCT03761108) is a global, single-arm, Phase 1/2 study of linvoseltamab, a BCMA×CD3 bispecific antibody, in patients with RRMM who were either triple-class exposed (TCE; previously treated with a proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody) during ≥3 prior lines of therapy (LOTs), or triple-class refractory to these therapies. Here, we present comparisons of clinical outcomes from LINKER-MM1 with those of a current, international, real-world (RW) external control arm (ECA; NCT05673967). Methods The ECA was derived from 16 academic sites of the International Myeloma Foundation International Myeloma Working Group (IMWG) (N=203; 309 eligible LOTs) and compared with linvoseltamab (N=105; Phase 2 200 mg cohort). Patients in the ECA initiated ≥1 anti-MM therapy after meeting key LINKER-MM1 eligibility criteria. Weighted random sampling and inverse probability of treatment weighting were used to select 1 LOT per patient and balance the ECA and trial populations on prespecified prognostic factors (Kumar S, et al. IMS 2023). The primary endpoint was objective response rate (ORR; IMWG criteria) determined by an independent central review committee (ICRC) based on myeloma laboratories. An independent data review committee reviewed comparability of cohorts and endpoint assessments prior to conducting comparative analyses. Results Median follow-up was 14.3 months for the linvoseltamab cohort (data cutoff: Jan 6, 2024) and 13.4 months for the ECA. After weighting, 15 prognostic factors were balanced between cohorts. Patients in the ECA received 68 distinct regimens, most commonly CAR T-cell therapies (11.3%) and ADCs (10.3%). After balancing the cohorts, patients in the ECA evaluable for response had ICRC-assessed ORR of 46.3% (40.8% by treating physician assessment), among whom 24.0% had very good partial response or better (≥VGPR). When including patients who died without evaluable response, ECA ICRC-assessed ORR was 44.2%. Linvoseltamab induced significantly higher ICRC-assessed ORR (69.5% vs 46.3%, odds ratio [OR] 2.65 [95% confidence interval (CI) 1.66-3.69]) and rate of ≥VGPR (62.9% vs 24.0%, OR 5.37 [95% CI 3.61-8.49]) compared with ECA regimens. Conclusion Despite current use of novel therapies, there is no well-established RW standard of care (SOC) for patients with TCE RRMM treated at IMWG sites. To our knowledge, this is the first RW ECA study in MM with a high percentage of anti-BCMA therapies and response ascertainment for all patients by ICRC. Linvoseltamab induced significantly higher response rates, including rate of ≥VGPR, compared with current RW SOC therapies, highlighting its potential as a highly effective treatment in patients with TCE RRMM.
Comparative Effectiveness of Linvoseltamab Versus Current Real-World (RW) Standard-of-Care (SOC) Therapies in Triple-Class Exposed Relapsed/Refractory Multiple Myeloma (RRMM): Key Subgroups Analysis
Kumar, Shaji, Dachs, Laura Rosiñol, Leleu, Xavier , Rubia, Javier de la , Mateos, María‐Victoria , Martínez, Borja Puertas, Gozzetti, Alessandro , Bladé, Joan , Beksaç, Meral , Escalante, Fernando , Nagaraj, Madhu , Hassan, Rafla , Spin, Paul , Bonar, Nicolle , Siddiqui, Muhaimen, Hou, Kevin, Green, Jeannette, Breskin, Alexander , Harnett, James , Ge, Wenzhen , Jalbert, Jessica J. , Kroog, Glenn S. , Lorenc, Karen Rodriguez , Ma, Qiufei , Durie, Brian G.M. , Gozzetti, Alessandro , Kumar, Shaji , Jagannath, Sundar , Weisel, Katja C , Dimopoulos, Meletios Α. , Siegel, David S. , Monge, Jorge , Du, Juan , Lee, Jae Hoon , Puertas, Borja , Dytfeld, Dominik , Ocio, Enrique M. , Ozaki, Shuji , Shokoohi, Mostafa , Wang, Di, Humblet, Olivier , Sobel, Rachel E. , Hampp, Christian

Blood | December 5, 2024 | Volume: 144 | Issue: Supplement 1 | Pages: 7012-7012

10.1182/blood-2024-200679 Get It

Introduction Linvoseltamab is an investigational, BCMA×CD3 bispecific antibody designed for the treatment of RRMM. High objective response rates (ORR) to linvoseltamab 200 mg in the LINKER-MM1 trial (NCT03761108) were demonstrated across high-risk subgroups, including patients aged ≥75 years, patients with high-risk cytogenetics, and patients with penta-class refractory status. The aim of this study was to compare ORR, overall and in key subgroups, between patients in Phase 2 of the LINKER-MM1 trial and patients in an international RW SOC external control arm (ECA). Methods The ECA was derived from a chart review of 16 academic sites across 10 countries that are part of the International Myeloma Foundation (IMF)-International Myeloma Working Group (IMWG) and 2 US electronic health record databases (COTA and Guardian Research Network [GRN]). Included patients initiated ≥1 anti-MM treatment after meeting key eligibility criteria of LINKER-MM1. Weighted random sampling and inverse probability of treatment weighting (IPTW) were used to select 1 line of therapy (LOT) per patient and balance the overall ECA and trial populations on prespecified prognostic factors (Kumar S, et al. IMS 2023). For ORR assessment, LINKER-MM1 and IMF-IMWG used independent central review committees per IMWG criteria, COTA used algorithmic assessment based on IMWG criteria, and GRN used physician-assessed responses. Prior to conducting comparative analyses, an independent committee of epidemiology and oncology experts reviewed the comparability of the cohorts and endpoint assessments, and approved study continuation. ORR among patients in LINKER-MM1 and patients in the ECA was compared overall and across prespecified subgroups (≥10 patients per subgroup), including age, race, cytogenetic risk score, international Staging System (ISS), presence of extramedullary plasmacytoma (EMP), refractory class, bone marrow plasma cell (BMPC) proportion, and number of prior LOTs. Results Median duration of follow-up was 14.3 months (data cut-off: January 6, 2024) for patients receiving linvoseltamab (n=105) and 13.6 months for the ECA (n=307; n=194, n=72, and n=41 from IMF-IMWG, COTA, and GRN, respectively). Following IPTW, 13 prognostic factors with <30% missingness were balanced between cohorts, with an effective sample size in the ECA of 197. After adjustment, ORR was significantly higher in patients who received linvoseltamab compared with patients in the ECA (69.5% vs 45.7%, odds ratio [OR] 2.5 [95% confidence interval (CI) 1.6-4.1]) and in key subgroups with age 65-74 years (76.9% vs 48.3%, OR 3.6 [1.6-8.6]), age ≥75 years (72.4% vs 48.5%, OR 2.8 [1.1-7.4]), Black or African American race (82.4% vs 25.0%, OR 14.0 [3.0-85.4]), White race (68.9% vs 49.7%, OR 2.2 [1.3-4.0]), standard cytogenetic risk (72.3% vs 51.3%, OR 2.5 [1.3-4.8]), ISS stage III (58.8% vs 19.7%, OR 5.8 [1.5-25.2]), absence of EMP (71.6% vs 49.3%, OR 2.6 [1.5-4.6]), triple-class refractory status (68.2% vs 45.7%, OR 2.6 [1.5-4.4]), quadruple-class refractory status (66.7% vs 45.9%, OR 2.4 [1.3-4.3]), 4-5 prior LOTs (65.1% vs 40.4%, OR 2.8 [1.3-6.0]), and >5 prior LOTs (75.7% vs 36.1%, OR 5.5 [2.4-13.6]). Numerically higher (not statistically significant) or similar ORR was observed for patients receiving linvoseltamab compared with patients in the ECA with age <65 years (59.5% vs 46.8%, OR 1.7 [0.79-3.6]), high-risk cytogenetics (65.0% vs 63.1%, OR 1.1 [0.41-2.9]), ISS stage I (73.3% vs 64.6%, OR 1.5 [0.62-3.7]), ISS stage II (67.6% vs 53.5%, OR 1.8 [0.72-4.7]), presence of EMP (58.8% vs 56.9%, OR 1.1 [0.32-3.8]), penta-class refractory status (64.3% vs 48.5%, OR 1.9 [0.78-4.8]), BMPC <50% (77.0% vs 67.2%, OR 1.6 [0.61-4.3]), BMPC ≥50% (41.7% vs 36.0%, OR 1.3 [0.36-4.7]), and ≤3 prior LOTs (68.0% vs 66.4%, OR 1.1 [0.43-2.9]). Separate findings will be presented for IMF-IMWG and COTA/GRN data at the congress. Conclusions Linvoseltamab induced better ORR vs RW SOC treatments overall, and better or similar ORR in the key subgroups assessed, highlighting its therapeutic value across a range of patients with RRMM with heterogeneous risk profiles and levels of disease burden.
Comparative effectiveness of linvoseltamab versus standard-of-care (SOC) treatment (tx) in real-world patients (pts) in the United States (US) with triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM).
Kumar, Shaji , Ma, Qiufei , Bonar, Nicolle , Spin, Paul , Harnett, James , Ge, Wenzhen , Jalbert, Jessica J. , Kroog, Glenn S. , Rodriguez-Lorenc, Karen, Weisel, Katja C , Hampp, Christian , Humblet, Olivier , Shokoohi, Mostafa , Sobel, Rachel E. , Jagannath, Sundar

Journal of Clinical Oncology | June 10, 2024 | Volume: 42 | Issue: 16_suppl | Pages: 7561-7561

10.1200/jco.2024.42.16_suppl.7561 Get It

7561 Background: Pts with TCE RRMM have poor outcomes and a high unmet need, with no established SOC tx. LINKER-MM1 (NCT03761108) is a single-arm, Phase 1/2 study investigating linvoseltamab, a B-cell maturation antigen × CD3 bispecific antibody, in pts with RRMM who were previously treated with a proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody, or were triple-class refractory (TCR) to these tx. The aim of this study was to contextualize LINKER-MM1 by comparing outcomes with linvoseltamab vs a real-world (RW) external control arm (ECA). Methods: A RW ECA was derived from 2 US electronic health record databases (COTA, Guardian Research Network) of pts who started a new line of therapy (LOT) after classification as TCE or TCR and met key eligibility criteria for LINKER-MM1. Eligibility was assessed at the initiation of each new LOT, and all eligible LOTs were included in the ECA. Data in Phase 2 pts who received linvoseltamab 200 mg in LINKER-MM1 were included (data cutoff: Sep 8, 2023). Inverse probability of tx weighting (IPTW) was used to reduce imbalances between the RW and LINKER-MM1 cohorts. Key prognostic factors were identified using a systematic review and rank ordered by an international committee of MM experts (Kumar et al., 2023). Outcomes included overall response rate (ORR), progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS). An independent committee of epidemiology and oncology experts reviewed the comparability of the cohorts and endpoint assessments prior to conducting comparative analyses. Results: Comparative analyses were performed in 105 pts in the linvoseltamab cohort and 101 RW pts (137 LOTs). Following IPTW, the distribution of cytogenetic risk, age, TCR status, Eastern Cooperative Oncology Group Performance Status, and platelet count were balanced between the 2 cohorts (absolute standardized mean difference <0.10). After adjustment, pts receiving linvoseltamab had significantly improved ORR, PFS, TTNT, and OS vs the RW ECA (see table). Conclusions: Linvoseltamab significantly improved outcomes vs RW SOC in the US, highlighting its potential as a highly effective tx in pts with TCE RRMM. [Table: see text]
Use of CAR T cell vs non-CAR T cell therapy in the treatment of patients (pts) with multiple myeloma (MM) in the Medicare population.
An, Na, Qian, Xia , Ge, Wenzhen , Wu, Ning , Rodriguez-Lorenc, Karen, Kroog, Glenn S. , Jalbert, Jessica J. , Harnett, James , Roccia, Tito , Ma, Qiufei , Ailawadhi, Sikander , Inocencio, Timothy J. , An, Na, Humblet, Olivier , Wu, Ning

Journal of Clinical Oncology | June 3, 2024 | Volume: 42 | Issue: 16_suppl | Pages: e23310-e23310

10.1200/jco.2024.42.16_suppl.e23310 Get It

e23310 Background: Chimeric antigen receptor T-cell therapy (CAR T) is FDA-approved in pts with triple-class exposed (TCE) relapsed/refractory (RR) MM after four or more prior lines of therapy (LOTs). Real-world access to CAR T remains challenging due to manufacturing capacity, financial barriers, and pt fitness. Pts with certain pre-existing comorbidities (e.g., central nervous system disease, heart disease, secondary malignancies) are commonly excluded from clinical trials, including those investigating CAR T. The objective of this study was to identify the factors associated with the use of CAR T in pts with TCE RRMM to better understand the unmet need in this population. Methods: We conducted an observational cohort study using Medicare fee-for-service data; each pt in the CAR T intention-to-treat (ITT) population between 2021 and 2023 was matched to three non-CAR T pts, without replacement. Pts were eligible if they had an initial MM diagnosis, were continuously enrolled, were TCE, and did not receive treatment in a clinical trial. The index date was the ITT date. Baseline characteristics included age, sex, race/ethnicity, census region, three comorbidity indexes (Charlson, Elixhauser, CMS hierarchical condition categories [HCCs]), a claims-based frailty index (CFI), and dual enrollment in Medicare and Medicaid (as a proxy to social economic status [SES]). Logistic regression was used to derive odds ratios (ORs) and 95% confidence intervals (CIs) comparing the characteristics of CAR T vs non-CAR T pts. Results: Seventy-three ITT CAR T pts (nine underwent apheresis but did not receive CAR T) were matched to 219 non-CAR T pts by LOT and index year. Matched pts were treated with varied standard regimens (daratumumab-containing: 63%). Median prior LOTs were similar in the two cohorts (8; range 2–13). Median time from MM diagnosis to index date was 44.6 and 51.9 months for CAR T and non-CAR T pts, respectively. Compared with non-CAR T pts, pts in the CAR T population were younger (aged < 75 years: 59% CAR T vs 36% non-CAR T), less frail (mean CFI: 0.18 vs 0.20) and had higher SES (without dual enrollment in Medicare and Medicaid: 96% vs 81%), but were similar in terms of sex, region, and race/ethnicity. Variation in individual comorbidity prevalence was observed between CAR T and non-CAR T pts. In a multivariable regression analysis, factors strongly associated with lower odds of CAR T use included age ≥75 years (OR 0.29; 95% CI 0.16–0.53), comorbidities (lung/other severe cancers [OR 0.39; 95% CI 0.20–0.74] and chronic obstructive pulmonary disease [OR 0.32; 95% CI 0.10–0.99] defined by HCCs), and SES (OR 0.09; 95% CI 0.02–0.37). Conclusions: Older age, certain comorbidities, and lower SES are associated with lower odds of receiving CAR T in real-world pts with TCE RRMM, demonstrating an unmet need for more accessible and effective treatment options with acceptable safety profiles for these pts.
Preferences among patients with triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM) in the era of B-cell maturation antigen (BCMA)-directed T-cell–engaging therapies.
Mansfield, Carol , Bussberg, Cooper , Chi, Lei, Harnett, James , Kroog, Glenn S. , Houvras, Yariv , Rodriguez-Lorenc, Karen, Ma, Qiufei , Ailawadhi, Sikander , Inocencio, Timothy J. , Chintakayala, Phani

Journal of Clinical Oncology | June 3, 2024 | Volume: 42 | Issue: 16_suppl | Pages: e23309-e23309

10.1200/jco.2024.42.16_suppl.e23309 Get It

e23309 Background: BCMA-directed T-cell–engaging therapies have been introduced into clinical practice for the treatment of TCE RRMM. While efficacious, such treatments are associated with safety considerations such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and serious infections. These treatments also vary in reported efficacy, administration processes, and hospitalization requirements. The aim of this study is to quantify patient preferences and tradeoffs regarding these attributes. Methods: A discrete choice experiment (DCE) was designed to elicit preference weights corresponding to seven attributes related to efficacy (objective response rate [ORR], overall survival [OS]), safety (all-grade CRS, all-grade ICANS, serious infections) and treatment procedures (treatment administration, hospitalization requirements). Attribute levels were based on plausible ranges of potential values. Patients in the United States (US) with a physician-confirmed diagnosis of TCE RRMM were recruited. Pre-test interviews with patients were conducted and the final survey deployed online in 2023. A random-parameters logit model was used to estimate preference weights. Conditional relative importance (CRI) was calculated to rank the relative importance of each attribute. The minimum acceptable benefit (MAB) and maximum acceptable risk (MAR) were calculated to estimate the tradeoffs between efficacy and safety attributes. Results: The sample included 200 respondents (mean [standard deviation] age: 61 [6.4] years; 43% female; 46% White; 10% African American). A total of 197 participants reported having responded to prior treatment, of whom 195 had relapsed or become refractory. In the DCE, a 24-month increase in OS was found to be the most important attribute, with a CRI of 32.0%. Next most important were avoiding a 60% risk of serious infection (CRI 17.3%), avoiding 14-day hospitalization requirements (CRI 15.0%), and a 38% increase in ORR (CRI 13.7%). A treatment that could be started immediately and administered weekly or up to every 4 weeks was preferred over a CAR T-like procedure with a waiting period. Fewer initial hospitalization days was significantly preferred over more hospitalization days. The MABs for OS when the risk of serious infection was increased from 20% to 60%, CRS from 40% to 95%, and ICANS from 3% to 20% were 24.2, 17.1, and 18.0 months, respectively. When OS was increased from 12 to 36 months, the estimated MARs for serious infections, CRS, and ICANS were > 60%, > 95%, and > 20%, respectively. Conclusions: This study highlights US patient preferences regarding treatment attributes for TCE RRMM. Treatment benefits and risks and the mutual tradeoffs considered by patients should be evaluated when developing and selecting therapeutic approaches.