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Multicenter Study
. 2024 Jun 6;17(1):42.
doi: 10.1186/s13045-024-01555-4.

Impact of extramedullary multiple myeloma on outcomes with idecabtagene vicleucel

Saurabh Zanwar #  1 , Surbhi Sidana #  2 , Leyla Shune #  3 , Omar Castaneda Puglianini  4 , Oren Pasvolsky  5 , Rebecca Gonzalez  4 , Danai Dima  6 , Aimaz Afrough  7 , Gurbakhash Kaur  7 , James A Davis  8 , Megan Herr  9 , Hamza Hashmi  8   10 , Peter Forsberg  11 , Douglas Sborov  12 , Larry D Anderson Jr  7 , Joseph P McGuirk  3 , Charlotte Wagner  12 , Alex Lieberman-Cribbin  13 , Adriana Rossi  13 , Ciara L Freeman  4 , Frederick L Locke  4 , Shambavi Richard  13 , Jack Khouri  6 , Yi Lin  1 , Krina K Patel #  14 , Shaji K Kumar #  15 , Doris K Hansen #  16
Affiliations
Multicenter Study

Impact of extramedullary multiple myeloma on outcomes with idecabtagene vicleucel

Saurabh Zanwar et al. J Hematol Oncol. .

Abstract

Idecabtagene vicleucel (Ide-cel) has demonstrated excellent efficacy and durable responses in patients with relapsed/refractory multiple myeloma (RRMM). However, the outcomes with ide-cel in patients with extramedullary disease (EMD) remain incompletely characterized. We included patients with RRMM treated with ide-cel between May 2021 and April 2023 across 11 US academic institutions. Visceral or soft tissue lesions non-contiguous from bone was classified as EMD. Time-to-event analyses were performed from date of ide-cel infusion. Among 351 patients, 84 (24%) had EMD prior to infusion. The median follow-up from ide-cel infusion was 18.2 months (95% CI: 17-19.3). The day 90 overall response rates (ORR) were 52% vs. 82% for the EMD and non-EMD cohorts, respectively (p < 0.001). The median progression-free survival (PFS) was 5.3 months (95% CI: 4.1-6.9) for the EMD cohort vs. 11.1 months (95% CI: 9.2-12.6; p < 0.0001) for the non-EMD cohort. In a multivariable analysis, EMD was an independent predictor of inferior PFS [hazard ratio 1.5 (1.1-2.2), p = 0.02]. The median overall survival was 14.8 months [95% CI: 9-Not reached (NR)] vs. 26.9 months (26.3 vs. NR, p = 0.006) for the EMD and non-EMD cohorts, respectively. Extramedullary disease represents an independent predictor of inferior day 90 ORR and PFS among patients treated with ide-cel.

Keywords: BCMA CAR-T; Ide-cel; Immunotherapy; Radiation; Relapsed/refractory myeloma.

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Conflict of interest statement

S.Z., O.P, R.G., D.D. G.K, M.H, P.F, C.W.A.L-C.: no relevant disclosures. S.S.: Consulting or advisory role for Janssen, Bristol-Myers Squibb, Legend, Magenta Therapeutics, Sanofi, Pfizer, Takeda, Kite, Abbvie and Regeneron; Research funding from Janssen, Magenta Therapeutics, Allogene Therapeutics, Novartis and Bristol-Myers Squibb; L.S.: Consulting or Advisory role for Janssen Oncology; O.C.P.: Consulting or Advisory role for BMS/Celgene/Juno, Legend Biotech; A.A.: Consulting or Advisory role for BMS, Karyopharm, Research funding from Abbvie, Adaptive biotechnologies; J.A.D.: consultancy for Janssen; H.H.; Consulting or Advisory role for Sanofi, BMS/Celgene, Janssen; speaker’s bureau: Janssen, Karyopharm, Amgen; D.S.: Consulting or Advisory role for Sanofi, GSK, BMS/Celgene, Janssen, Abbvie, Pfizer, Arcellx, BiolineRx, Astrazeneca, research funding from Pfizer; L.D.A. Jr: consulting or advisory board role for Janssen, Celgene, Bristol Myers Squibb, Amgen, GlaxoSmithKline, AbbVie, BeiGene, Cellectar, Sanofi, Karyopharm, Oncopeptides, and Prothena. J.M: Honoraria: Kite, a Gilead company, AlloVir, Magenta Therapeutics, Nektar, Sana Biotechnology; Consulting or Advisory Role: Kite, a Gilead company, Juno Therapeutics, AlloVir, Magenta Therapeutics, EcoR1 Capital, CRISPR therapeutics; Speakers’ Bureau: Kite/Gilead; Research Funding: Novartis (Inst), Fresenius Biotech (Inst), Astellas Pharma (Inst), Bellicum Pharmaceuticals (Inst), Novartis (Inst), Gamida Cell (Inst), Pluristem Therapeutics (Inst), Kite, a Gilead company (Inst), AlloVir (Inst); Travel, Accommodations, Expenses: Kite, a Gilead company; A.R.: consultant for Sanofi, BMS, Janssen, and Adaptive. C.R. is a consultant for Janssen, BMS, Takeda, Sanofi, and Artiva; C.L.F: horonoraria and consulting- Bristol Myers Squibb, Seattle Genetics, Celgene, AbbVie, Sanofi, Incyte, Amgen, ONK Therapeutics & Janssen; and research funding from Bristol Myers Squibb, Janssen, and Roche/Genentech; F.L.L.: Scientific Advisory Role/Consulting Fees: A2, Allogene, Amgen, Bluebird Bio, BMS, Calibr, Caribou, Cowen, EcoR1, Gerson Lehrman Group (GLG), Iovance, Kite Pharma, Janssen, Legend Biotech, Novartis, Sana, Umoja, Pfizer; Data Safety Monitoring Board: Data and Safety Monitoring Board for the NCI Safety Oversight CAR T-cell Therapies Committee. Research Contracts or Grants to my Institution for Service: Kite Pharma (Institutional), Allogene (Institutional), CERo Therapeutics (Institutional), Novartis (Institutional), BlueBird Bio (Institutional), 2SeventyBio (Institutional), BMS (Institutional), National Cancer Institute (R01CA244328 MPI: Locke; P30CA076292 PI: Cleveland), Leukemia and Lymphoma Society Scholar in Clinical Research (PI: Locke); Patents, Royalties, Other Intellectual Property: Several patents held by the institution in my name (unlicensed) in the field of cellular immunotherapy; Education or Editorial Activity: Aptitude Health, ASH, BioPharma Communications CARE Education, Clinical Care Options Oncology, Imedex, Society for Immunotherapy of Cancer S.R.: Honoraria: BMs, Jansssen; Consulting or Advisory Role: Genentech; Research Funding: Janssen, C4 therapeutics, Gracell, Heidelberg Pharma; J.K.: Consulting or Advisory Role: Janssen Oncology; Honoraria: GPCR therapeutics; Y.L.: Consulting or Advisory role: Kite/Gilead, BMS, Vineti, Janssen Oncology, Pfizer; Sanofi, NexImmune, Caribou biosciences, Regeneron, Genentech, Fosun Kite, Chimeric Therapeutics, Adicet Bio, Nektar; Research Funding: Janssen Oncoloyg, BMS, Merck, Takeda, Boston Scientific, Kite/Gilead, Bluebird Bio; K.K.P.: Consulting or Advisory Role: Celgene, BMS, Janssen, Pfizer, Arcellx, Karyopharm Therapeutics, Merck, Cellectis, Caribou Biosciences, Takeda, Abbvie, Travel, Accomodation, Expenses: BMS; Research funding: Celgene/BMs, Takeda, Janssen, Cellectis, Nektar, Abbvie/Genentech, Precision Biosciences, Allogene Therapeutics; S.K.: Consulting or Advisory Role: Takeda, Janssen Oncology, Genentech/Rocher, Abbvie, BMS/Celgene, Pfizer, Regeneron, Sanofi, K36 Therapeutics; travel, accomodation and expenses: Abbvie, pfizer; Research funding: Takeda, Abbvie, Novartis, Sanofi, Janssen Oncology, MedImmune, Roche/Genentech, CARsgen Therapeutics, Allogene Therapeutics, GSK, Regeneron, BMS/Celgene; D.K.H.: Research funding from Bristol-Myers Squibb, Karyopharm, and Adaptive Biotech; Consulting or advisory role for Bristol-Myers Squibb, Janssen, Pfizer, and Karyopharm. D.K.H is also supported by the Pentecost Family Myeloma Research Center.

Figures

Fig. 1
Fig. 1
Response rates at Day 30 and Day 90 by the IMWG criteria: Patients with EMD demonstrate significantly inferior overall response rates (ORR) at day 90 (52%) compared to the non-EMD cohort (82%, p < 0.001)
Fig. 2
Fig. 2
Survival Outcomes with ide-cel: A. Presence of extramedullary disease (EMD) was associated with a significantly inferior progression-free survival compared to the patients without EMD [hazard ratio 2.1 (95% CI: 1.6–2.7), p < 0.001]. B. Overall Survival was significantly inferior in the cohort of patients with EMD [Hazard ratio 1.6 (95% CI: 1.1–2.4), p = 0.007]
Fig. 3
Fig. 3
Progression-free survival (PFS) with ide-cel in patients with extramedullary disease (EMD). A. Patients with EMD achieving a day 30 objective response demonstrated a trend toward improved PFS but this did not reach statistical significance. B. The type of progression (hematologic, extramedullary or both) did not impact the PFS. C. Visceral site of EMD did not confer an inferior PFS with ide-cel and D. Presence of multi-site disease was not associated with a significantly worse PFS with ide-cel
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