Background

Multiple myeloma (MM) is a hematologic cancer characterized by an uncontrolled neoplastic proliferation of clonal plasma cells resulting in complications and death. Despite the discovery of novel agents, it remains an incurable disease. Elranatamab (Elra) is a humanized B-cell maturation antigen (BCMA)-CD3 bispecific antibody that was FDA approved in 2023 for the treatment of RRMM. We evaluated the outcomes of 34 patients (pts) treated with SOC Elra.

Methods

This retrospective analysis at Moffitt Cancer Center evaluated pts with RRMM that were treated with Elra between September 2023 and July 1, 2024. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded per ASTCT consensus criteria, while responses were graded based on the IMWG response criteria.

Results

Median age at the time of treatment was 69 years (52-81), and 6 (17.6%) out of the 34 pts evaluated had an ECOG performance status >2. Seventeen pts (50%) had high-risk cytogenetics by IMWG criteria (defined as del17, t(4;14), t(14;16)) at the time of initiation of Elra. Twenty-eight (82.3%) pts had a gain 1q identified. Median prior lines of therapy was 7 (4-14). As expected, this population was very heavily pretreated; thirty-three pts were triple-class refractory (97%), and twenty-four were penta-class refractory (70.6%). Twenty-six pts (76.5%) had previously received another anti-BCMA targeted therapy (BCMA-TT). Responses to prior BCMA-TT were as follows: 2 progression of disease (PD), 1 stable disease (SD), 4 partial response (PR), 1 very good partial response (VGPR), 18 complete response or better (≥CR). Seventeen of twenty-two pts tested for BCMA expression were positive by IHC. Of those that receive prior BCMA-TT, twenty (76.9%) had no other line of therapy (LOT) in between. Four pts (15.4%) had 1 LOT between prior BCMA-TT and Elra, and two pts (8.3%) had 2 LOT.

At a median follow up of 3.3 months, overall response rate (ORR) was 52.9%, with 5 pts achieving a PR, 2 a VGPR, and 11 a ≥CR. While 12 (35.3%) pts did not show any response to Elra, 3 (8.8%) had SD and 1 (2.9%) showed a minimal response (MR). Among the 12 pts that had progression of disease after Elra, 3 (25%) were naïve to BCMA directed therapies. All non-responders had previously benefited from other prior BCMA-TT. Nine (75%) of the non-responders had BCMA expression by IHC at the time of Elra administration.

Eleven (32.4%) pts had CRS. All CRS events were grade 1 (90.9) or grade 2 (9.1%) only. Five (14.7%), patients received Tocilizumab as part of the management for CRS. ICANS was seen in 5 pts (14.7%); 4 were ≤grade2, and only 1 grade 3. Infections were seen in eleven (32.4%) pts, and seven (63.6%) of those were severe requiring hospitalization. Six infectious cases were identified as bacterial, while 4 were viral. Four (11.8%) pts had severe neutropenia requiring granulocyte colony stimulating factor (GCSF). At the time of initiation of Elra seventeen (50%) pts had hypogammaglobulinemia, as defined by an IgG<400. After exposure to Elra, 9 pts (57%) developed new onset hypogammaglobulinemia. Thirteen (38.2%) pts receive intravenous immunoglobulin (IVIG). Ten pts died; 8 due to progressive myeloma, and 2 due to infection.

Conclusions

Patients treated with SOC Elra had a favorable ORR (52.9%) while maintaining an acceptable safety profile despite a larger proportion of them having high risk features relative to trial patients, including poor performance status, high-risk cytogenetics, and prior BCMA-directed therapies. Results will be updated with continued follow up.

*AFG, DKH, OC are co-first authors

Disclosures

Grajales-Cruz:Amgen: Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Cellectar: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Hansen:Karyopharm: Consultancy, Research Funding; Pfizer: Consultancy; Janssen: Consultancy; BMS: Consultancy, Research Funding. Castaneda:Janssen: Consultancy; BMS: Consultancy; Legend Biotech: Consultancy. Blue:Sanofi: Speakers Bureau; Pfizer Pharmaceuticals, Oncopeptides, Takeda, Abbvie, Janssen, and Kite Pharmaceuticals: Consultancy. Tobon:Eli Lilly: Consultancy, Honoraria, Other: Consultant/Advisory Board; Abbvie: Consultancy, Honoraria, Other: Consultant/Advisory Board; Bristol Myers Squibb: Consultancy, Honoraria, Other: Completed non-CE panel discussion. Liu:BioLineRx: Consultancy, Honoraria. Freeman:ONK therapeutics: Consultancy; Celgene: Consultancy; Seattle Genetics: Consultancy; Incyte: Consultancy; Amgen: Consultancy; Roche/Genentech: Research Funding; BMS: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Research Funding; Sanofi: Consultancy; Abbvie: Consultancy. Locke:American Society of Hematology: Honoraria, Other: travel, accomodation, expenses; Janssen: Consultancy; Amgen: Consultancy; BioPharma Communications CARE Education: Honoraria; Allogene: Other: Institutional, Research Funding; EcoR1: Consultancy; Society for Immunotherapy of Cancer: Honoraria; Gerson Lehrman Group (GLG): Consultancy; A2: Consultancy; Calibr: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; CERo Therapeutics: Research Funding; Kite, a Gilead Company: Consultancy, Other: institutional, travel, accomodation, expenses, Research Funding; Cowen: Consultancy; Allogene: Consultancy, Research Funding; Legend Biotech: Consultancy; Clinical Care Options Oncology: Honoraria; Moffitt Cancer Center: Patents & Royalties; Pfizer: Consultancy; Communications CARE Education: Honoraria; Bluebird Bio: Consultancy; Iovance: Consultancy; Novartis: Consultancy, Research Funding; Sana: Consultancy; Umoja: Consultancy; Imedex: Honoraria; Caribou: Consultancy; Aptitude Health: Honoraria; 2SeventyBio: Other: Institutional, Research Funding; National Cancer Institute: Other: Institutional, Research Funding; Leukemia and Lymphoma Society Scholar in Clinical Research: Other: Institutional, Research Funding. Nishihori:Novartis: Research Funding; Karyopharm: Other: drug only supply to the institution; ImmunoGen: Consultancy; Medexus: Membership on an entity's Board of Directors or advisory committees. Shain:Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Research Funding; Karyopharm: Research Funding; Abbvie: Research Funding; Karyopharm, Janssen, Adaptive Biotechnologies, GlaxoSmithKline, BMS, Sanofi, and Regeneron: Honoraria; Glaxo Smith Kline: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy; Takeda: Consultancy; Amgen: Research Funding; Adaptive Biotech: Consultancy. Alsina:BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees. Baz:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Cellectar: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Bristol-Myers Squibb: Research Funding; Karyopharm Therapeutics: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Regeneron: Research Funding; AbbVie: Research Funding.

This content is only available as a PDF.
2024
Sign in via your Institution