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4759 Efficacy of Idecabtagene Vicleucel (ide-cel) in Patients with Relapsed/Refractory Multiple Myeloma and Prior Central Nervous System Manifestation: A Retrospective Real-World Analysis

Program: Oral and Poster Abstracts
Session: 655. Multiple Myeloma: Cellular Therapies: Poster III
Hematology Disease Topics & Pathways:
Research, Clinical Research, Real-world evidence
Monday, December 9, 2024, 6:00 PM-8:00 PM

Markus Maulhardt1*, Philipp Berning2*, Christine Hanoun3*, Hristo Boyadzhiev4,5*, Anca Maria Albici6*, Snjezana Janjetovic7*, Anna Ossami Saidy7*, Simon Call2*, Natalie Schub6*, Enver Aydilek1*, Michael Daskalakis8*, Wolfram Jung1*, Justin Hasenkamp1*, Carolin Krekeler2*, Cyrus Khandanpour9, Ulrike Bacher8*, Hans Christian Reinhardt3, Georg Lenz2, Friedrich Stölzel6*, Gerald Wulf1*, Thomas Pabst4, Bastian von Tresckow3 and Evgenii Shumilov2*

1Department of Hematology and Medical Oncology, University Hospital Goettingen, Goettingen, Germany
2Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Muenster, Muenster, Germany
3Department of Hematology and Stem Cell Transplantation, West German Cancer Center and German Cancer consortium (DKTK partner site Essen), University Hospital Essen, University of Duisburg-Essen, Essen, Germany
4Department of Medical Oncology, Inselspital, University Hospital Bern, University of Bern, Bern, Switzerland
5Habichtswald Hospital, Kassel, Germany
6Division of Stem Cell Transplantation and Cellular Immunotherapies, University Hospital Schleswig-Holstein, Kiel, Germany
7Department of Hematology and Cell Therapy, Helios Klinikum Berlin-Buch, Berlin, Germany
8Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
9Department of Hematology and Oncology, University Hospital Schleswig-Holstein, University of Luebeck, Luebeck, Germany

Introduction

Relapsed/refractory (r/r) multiple myeloma (MM) with central nervous system (CNS) manifestation represents a significant therapeutic challenge, characterized by a poor prognosis with a median overall survival (mOS) of two months (mo). Concurrently, BCMA-directed chimeric antigen receptor (CAR)-T cell therapies have emerged as a standard of care treatment in r/r MM. However, real-world evidence regarding the efficacy and safety profile of CAR-T cell therapy in MM patients (pts) with a history of CNS disease (MM-CNS) is limited, as these were excluded from the pivotal studies. We therefore evaluated the outcomes of MM-CNS pts undergoing ide-cel and compared them to MM pts without CNS disease (non-MM-CNS) in a real-world setting.

Methods

We conducted a multicenter retrospective study including r/r MM pts undergoing ide-cel treatment between March 2022 and May 2024 at seven German tertiary care centers. Pts were grouped by presence of CNS disease prior to ide-cel infusion. Only pts with intradural and/or intraparenchymal lesions or detection of myeloma cells in the cerebrospinal fluid (CSF) were regarded as MM-CNS pts. Subsequently, descriptive and survival analyses, including propensity score matching between MM-CNS and non-MM-CNS pts (nearest neighbor 1:1 matching with R-ISS stage, number of therapy lines, triple- and penta-class refractoriness, and remission status as co-variates) were performed.

Results

In total, we identified 153 r/r MM pts undergoing ide-cel therapy during the specified period. Seventeen (11%) pts met the criteria of CNS disease prior to CAR-T treatment. The median age for MM-CNS pts at CAR-T infusion and the median number of therapy lines prior to ide-cel was 62 years (range: 32-81 years) and 5 (range: 3-11), respectively. Penta-refractoriness was documented in 12 (71%) cases. CNS manifestation prior to ide-cel occurred in two pts (12%) at initial diagnosis, while the remaining cases (15/17; 88%) developed secondary CNS involvement during the disease course and after a median of three therapy lines. Median time from first CNS myeloma detection to CAR-T therapy was 10 mo. One pt experienced CNS manifestation after indication to ide-cel. CNS manifestations were parenchymal lesions (50%), leptomeningeal manifestations (44%) and/or central nerve lesions (31%). CNS myeloma was commonly detected by MRI (20%), CT (27%), or both (47%) as well as imaging plus CSF diagnostics (7%). Regarding CNS myeloma status immediately before CAR-T cell therapy and defined by imaging +/- CSF diagnostics, complete remission (CR) was achieved in 20%, partial remission (PR) in 27%, stable disease (SD) in 20% and 33% of pts presented with progressive disease (PD) at CAR-T application. Serologic response at ide-cel infusion showed CR and VGPR/PR in 31% of MM-CNS pts each, respectively, while 13% had SD and 25% PD at CAR-T treatment.

Best radiologic response for CNS manifestation following ide-cel treatment was CR (69%) followed by PR (23%) and SD (8%) while PD did not occur. The best serologic response was: CR (47%), VGPR/PR in (35%) and PD in 18%. Overall, seven (41%) pts experienced relapse post-CAR-T. Of these, two (12%) pts experienced relapse or progression of CNS disease after ide-cel, while the remaining five pts developed serologic progression. Cytokine-release syndrome (CRS) grade >2 occurred in 19% (gr.3: 13%; gr.4: 6%). Notably, there were no cases of high-grade (3-4) immune effector cell-associated neurotoxicity syndrome (ICANS). With a median follow-up of 4.4 months, estimated median progression-free survival (mPFS) for MM-CNS pts was 10.5 mo while mOS was not reached; 1-year OS was 88%. Survival outcomes as well as serologic response rates were consistent after applying propensity score matching identifying a cohort of 17 pts without CNS myeloma undergoing ide-cel therapy: mPFS 10.5 vs. 8.5 mo (p=0.59), mOS 13 vs. 10.6 mo (p=0.92); CR/VGPR/PR rates 82% and 80%, for MM-CNS and non-MM-CNS pts, respectively.

Conclusions

We here report for the first time that CAR-T cell therapy is an effective and feasible treatment option in MM-CNS pts, showing comparable outcomes to those without a history of CNS myeloma. Our data showed a high remission rate for CNS manifestations after ide-cel treatment. Therefore, CAR-T cell therapy can be considered for eligible r/r MM patients with a history of CNS involvement.

Disclosures: Schub: BMS, Janssen: Honoraria. Aydilek: Kite Gilead: Honoraria. Daskalakis: Kite Gilead, Novartis: Other: Travel and congress support ; Novartis: Consultancy, Honoraria. Lenz: Bayer: Honoraria, Research Funding; BMS: Honoraria; Constellation: Honoraria; Genase: Honoraria; Genmab: Honoraria; Hexal/Sandoz: Honoraria; Immagene: Honoraria; Incyte: Honoraria; Karyopharm: Honoraria; Lilly: Honoraria; Miltenyi Biotech: Honoraria; MSD: Honoraria; NanoString: Honoraria; PentixaPharm: Honoraria; Pierre Fabre: Honoraria; Sobi: Honoraria, Speakers Bureau; Acerta: Research Funding; Roche, Gilead, BMS, Novartis, AstraZeneca, Abbvie, Incyte, Genmab, Constellation, ADC Therapeutics, Miltenyi, PentixaPharm, Sobi, Immagene, Genase, Hexal-Sandoz, Lilly, Beigene, MSD, Pierre Fabre: Consultancy; ELVESCA: Current equity holder in private company; Roche, Gilead, BMS, Novartis, AstraZeneca, Abbvie, Incyte, Genmab, Constellation, ADC Therapeutics, Miltenyi, PentixaPharm, Sobi, Immagene, Genase, Hexal-Sandoz, Lilly, Beigene, MSD, Pierre Fabre: Membership on an entity's Board of Directors or advisory committees; AbbVie, BeiGene, Sobi, Roche, Gilead, BMS: Other: Travel; MorphoSys: Honoraria, Research Funding; BeiGene: Honoraria; Amgen: Honoraria; AbbVie: Honoraria; ADC Therapeutics: Honoraria; Verastem: Research Funding; Roche: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding; AGIOS: Research Funding; AQUINOX: Research Funding; Gilead: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. von Tresckow: AbbVie, AstraZeneca, BMS/Celgene, Gilead Kite, Incyte, Janssen-Cilag, Lilly, Merck Sharp & Dohme, Novartis, Roche and Takeda: Honoraria; Esteve (Inst), Merck Sharp & Dohme (Inst), Novartis (Inst), and Takeda (Inst): Research Funding; AbbVie, AstraZeneca, Gilead Kite, Janssen-Cilag, Lilly, Merck Sharp & Dohme, Pierre Fabre, Roche, Takeda, and Novartis: Other: Travel and congress support ; Allogene, Amgen, BMS/Celgene, Cerus, Gilead Kite, Incyte, IQVIA, Janssen-Cilag, Lilly, Merck Sharp & Dohme, Miltenyi, Novartis, Noscendo, Pentixapharm, Pfizer, Pierre Fabre, Qualworld, Regeneron, Roche, Sobi and Takeda: Consultancy. Shumilov: Oncopeptides: Consultancy, Honoraria, Other: Travel and congress support; Incyte: Honoraria; BMS: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Other: Travel and congress support; Pfizer: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Other: Travel and congress support; Stemline: Consultancy, Honoraria; Sanofi-Aventis: Consultancy, Honoraria, Other: Congress support.

*signifies non-member of ASH