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3792d Activity of CAR-T Cells and Bispecific Antibodies in Multiple Myeloma with Extramedullary Involvement

Program: Oral and Poster Abstracts
Session: 907. Outcomes Research: Plasma Cell Disorders: Poster II
Hematology Disease Topics & Pathways:
Research, Bispecific Antibody Therapy, Clinical Research, Health outcomes research, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Plasma Cell Disorders, Therapy sequence, Diseases, Treatment Considerations, Biological therapies, Real-world evidence, Adverse Events, Lymphoid Malignancies, Monoclonal Antibody Therapy
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Maximilian J. Steinhardt1*, Christoph Schaefers, MD2*, Lisa Leypoldt, MD2*, Marie Harzer2*, Xiang Zhou, MD, BMBS3, Christine Riedhammer, MD4*, Abdulaziz Kamili, MD2*, Ricardo Kosch, MD2*, Jule Arztenroth, MD2*, Maximilian Al-Bazaz, MD2*, Winfried Alsdorf5*, Max S. Topp4*, Johannes Duell, MD6*, Julia Mersi, MD1*, Johannes Waldschmidt, MD7, Carsten Bokemeyer, MD2*, Hermann Einsele, MD1, K. Martin Kortüm, MD8*, Katja C. Weisel, MD5 and Leo Rasche, MD9,10*

1Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany
2University Medical Center Hamburg Eppendorf, Hamburg, Germany
3University Hospital Wuerzburg, Wurzburg, Germany
4University Hospital Wuerzburg, Wuerzburg, Germany
5University Medical Center Hamburg-Eppendorf, Hamburg, Germany
6University of Wurzburg, Wurzburg, Germany
7Department of Internal Medicine II, University Hospital Wuerzburg, Wuerzburg, Germany
8Department of Internal Medicine II, University Hospital of Würzburg, Wuerzburg, Germany
9Department of Internal Medicine, University Hospital of Würzburg, Würzburg, Germany
10Mildred-Scheel-Nachwuchszentrum, Wuerzburg, Germany

Background

Extramedullary disease (EMD) represents an aggressive variant of multiple myeloma (MM) associated with low response rates to conventional myeloma therapies, short progression-free survival (PFS) and high mortality. While CAR T cells and bispecific antibodies (bsABs) provide new opportunities in patients with relapsed/refractory MM (RRMM), their use in EMD is less clear. Furthermore, it remains uncertain whether one strategy is superior to the other in the setting of EMD and should therefore be preferred.

Methods

We retrospectively collected data of patients with EMD not adjacent to the bone treated with bsABs or CAR T cell therapies from two academic centers in Germany from 09/21 to 07/24. All patients had both serological assessment and EMD imaging prior to therapy initiation and follow-up after at least three months or at the point of progression. We analyzed demographics, outcomes, cytogenetics, and prior therapies.

Results

We enrolled all 78 RRMM patients with EMD treated with either cilta-cel (n=11), ide-cel (n=21), talquetamab (n=27), and teclistamab (n=18). Muscle (38%), skin (33%), pleural (30%) and retroperitoneal manifestations (22%) were the most common EMD localizations, and the median follow-up was 4.6 months.

The four cohorts were comparable with a median of 5 to 7 prior lines of therapy. EMD was diagnosed 2.5-4 years after MM diagnosis. All patients were triple-refractory and more than 64% were penta-refractory in each cohort. The population was enriched for high-risk cytogenetics (>41% of patients with available FISH over all cohorts). The majority of CAR T cell patients received bridging therapy. Response to bridging therapy was not associated to PFS and 41/36% had extramedullary or serologic progressive disease at the time of cilta-cel or ide-cel cell infusion, respectively. The vast majority of patients receiving cilta-cel, ide-cel or teclistamab were BCMA-naive (>91% in each cohort).

EMD response rates of patients receiving CAR T cells were significantly higher (93% for cilta-cel, 82% for ide-cel) than with bsABs (47% for talquetamab, 38% for teclistamab, p<0.0001). Complete resolution of EMD was also significantly more frequent after CAR T cell therapies (50% and 41%) than after bsABs (16% and 14%, p=0.001). Median PFS was not reached in patients after cilta-cel and significantly longer in ide-cel with 11.2 months when compared to talquetamab and teclistamab (3.2 and 2.8 months, p=0.03). OS was not reached for patients receiving cilta-cel, 24.6 months for ide-cel, 18.4 months for teclistamab, and 15.1 months for Talquetamab (ns).

Serologic response ≥PR in patients with measurable serologic activity predicted EMD response (p<0.0001).

Independent of treatment, visceral and soft tissue manifestations responded significantly less frequent than skin, mucosal, and lymph node lesions (p=0.02).

Conclusion

Both CAR T cells and bsABs show efficacy in EMD. However, CAR T cells appear to be superior to bsABs in this setting. With significantly higher response rates, deeper remissions and longer median PFS in our analysis, CAR T cells may provide a meaningful benefit in EMD and should be considered preferentially.

Disclosures: Steinhardt: Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Other: Travel funds; Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees. Schaefers: Janssen: Honoraria; Abbvie: Honoraria; Astra Zeneca: Honoraria; Pfizer: Consultancy; Janssen: Consultancy; Astra Zeneca: Consultancy; Bristol Myers Squibb: Research Funding; Sanofi: Other: Travel Expenses; Menarini Stemline: Other: Travel Expenses; Acus Health: Other: Travel Expenses. Leypoldt: Oncopeptides: Other: travel expenses; Abbvie: Honoraria, Research Funding; BMS/Celgene: Honoraria; Pfizer: Honoraria; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive: Honoraria; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel expenses. Kamili: Janssen: Other: Travel Expenses. Kosch: Amgen: Other: Tra. Alsdorf: Immatics: Consultancy, Other: Travel costs, accommodations, expenses, assistance in medical writing; Janssen: Consultancy, Honoraria, Other: Travel costs, accommodations, expenses, assistance in medical writing; Affimed: Research Funding; Biontech: Other: Travel costs, accommodations, expenses, assistance in medical writing, Research Funding; AstraZeneca: Honoraria; Astellas: Honoraria; GSK: Honoraria. Topp: Roche: Honoraria, Other: Travel Support, Research Funding; Autolus Therapeutics: Consultancy; AbbVie: Consultancy; Incyte: Consultancy; Kite, a Gilead Company: Honoraria, Research Funding; Regeneron Pharmaceuticals, Inc.: Honoraria, Research Funding; Universitatsklinikum Wurzburg: Current Employment; AstraZeneca: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria. Duell: BMS: Honoraria; Gilead-Kite: Honoraria; Janssen: Honoraria; Novartis: Honoraria; Incyte: Consultancy, Research Funding; Abbvie: Consultancy; Beigene: Consultancy. Waldschmidt: Sanofi: Consultancy; Janssen: Consultancy; Takeda: Consultancy; Oncopeptides: Consultancy; Stemline Menarini: Consultancy; Pharmamar: Honoraria; GSK: Honoraria; Pfizer: Honoraria; Beigene: Honoraria. Bokemeyer: Astra Zeneca: Honoraria; Berlin Chemie: Honoraria; AOK Germany: Honoraria; Bristol Myers Squibb: Honoraria; GSO Research Organization: Honoraria; Janssen: Honoraria; med update: Honoraria; Merck Serono: Honoraria; Merck Sharp & Dohme: Honoraria; Novartis: Honoraria; Sanofi Aventis: Honoraria. Einsele: Sanofi: Honoraria; Celgene/Bristol-Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Honoraria; Amgen: Honoraria, 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, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kortüm: AbbVie, BMS, GSK Janssen, Novartis, Pfizer, Sanofi, Takeda, Stemline: Honoraria; AbbVie, BMS, GSK Janssen, Novartis, Pfizer, Sanofi, Takeda, Stemline: Consultancy; University Hospital Wurzburg: Current Employment. Weisel: Stemline: Honoraria; GlaxoSmithKline: Consultancy, Honoraria, Other: Research grant to institution; Pfizer: Consultancy, Honoraria; Novartis: Honoraria; Oncopeptides: Consultancy, Honoraria; BeiGene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Other: Research grant to institution; Roche Pharma: Consultancy, Honoraria; AstraZeneca: Honoraria; Adaptive Biotechnologies: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Other: Research grant to institution; AbbVie: Other: Research grant to institution; Menarini: Consultancy, Honoraria; Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Other: Research grant to institution; Janssen: Consultancy, Honoraria, Other: Research grant to institution; Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Regeneron: Consultancy. Rasche: Janssen: Honoraria; Skyline Dx: Research Funding; Pfizer: Honoraria; GSK: Honoraria; BMS: Honoraria; Amgen: Honoraria.

*signifies non-member of ASH