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Multicenter Study
. 2025 Jul 30;15(1):126.
doi: 10.1038/s41408-025-01330-9.

Activity of CAR-T cells and bispecific antibodies in multiple myeloma with extramedullary involvement

Maximilian J Steinhardt #  1 , Christoph Schaefers #  2 , Lisa B Leypoldt  2   3 , Igor-Wolfgang Blau  4 , Marie Harzer  2 , Xiang Zhou  1 , Christine Riedhammer  1 , Abdulaziz Kamili  2 , Ricardo Kosch  2 , Laura S Topp  1 , Isabel Molwitz  5 , Nils-Ole Gross-Fengels  5 , Yasmin Fede Melzer  5 , Jule Artzenroth  2 , Maximilian Al-Bazaz  2 , Winfried Alsdorf  2 , Max S Topp  1 , Johannes Duell  1 , Julia Mersi  1 , Johannes Waldschmidt  1 , Carsten Bokemeyer  2 , Hermann Einsele  1 , K Martin Kortüm  1 , Katja Weisel  2 , Leo Rasche  6   7
Affiliations
Multicenter Study

Activity of CAR-T cells and bispecific antibodies in multiple myeloma with extramedullary involvement

Maximilian J Steinhardt et al. Blood Cancer J. .

Abstract

Extramedullary multiple myeloma (EMD) is associated with low response rates, short progression-free survival, and poor prognosis. CAR T cells and bispecific antibodies (bsABs) have shown efficacy in relapsed myeloma, but it remains uncertain whether one T cell redirection strategy should be preferred. We retrospectively analyzed 80 patients with EMD not adjacent to the bone treated with ide-cel, cilta-cel, teclistamab, or talquetamab at three academic centers in Germany. All patients were heavily pretreated, and a high-risk cytogenetic profile was prevalent in >41% of patients. All cohorts had a median of 5 to 7 prior lines of therapy. The vast majority of patients receiving cilta-cel, ide-cel, or teclistamab were BCMA-naive ( >88%). Response rates after CAR T cell infusion were significantly higher (100% with cilta-cel, 82% with ide-cel) than with bsABs (29% for talquetamab, 36% for teclistamab). Complete resolution of EMD was more frequent after CAR T cell therapies (50% and 41%) than after bsABs (16% and 14%). With a median follow-up of 12.2 months, median (m)PFS was not reached in patients that had received cilta-cel; mPFS was 7.3 months after ide-cel and significantly longer for both CAR T products compared to talquetamab or teclistamab (mPFS 4.0 and 2.6 months). Effective debulking therapy prolonged remissions after CAR T cell infusion compared to no debulking or no response to debulking. Visceral and soft tissue manifestations responded significantly less frequently than EMD in other locations. With significantly higher response rates, deeper remissions, and longer mPFS, our retrospective data suggest CAR T cells may provide a meaningful benefit in EMD.

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Conflict of interest statement

Competing interests: MJS: Travel funds from and consultancy for Johnson&Johnson outside of the submitted work. CS: Consultancy for Acus Health, Astra Zeneca, Janssen-Cilag, Menarini Stemline, oncopeptides, Pfizer; honoraria from Abbvie, Astra Zeneca, Janssen-Cilag; other (travel expenses/congress support): Acus Health, Astra Zeneca, Janssen-Cilag, Menarini Stemline, oncopeptides, Sanofi. LBL: Advisory role: GSK, Sanofi, Janssen; Honoraria-payments for specific speeches, seminar presentations, or appearances: Adaptive, AbbVie, Janssen, BMS/Celgene, Pfizer, Sanofi, GSK, Takeda, AstraZeneca; Research funding: Abbvie, GSK (both to the institution); Travel: Sanofi, Oncopeptides, J&J I-WB states no conflicts of interest. MH states no conflicts of interest. XZ states no conflicts of interest. CR received honoraria from Janssen. AK states no conflicts of interest. RK states no conflicts of interest. LST states no conflicts of interest. IM states no conflicts of interest. N-OG-F states no conflicts of interest. YFM states no conflicts of interest. JA: Travel funds from Sanofi. MA-B states no conflicts of interest. WA: Honoraria from GSK, Janssen, Astellas, AstraZeneca. Research Funding: Affimed, Biontech. Consultancy: Janssen, Immatics. ST states no conflicts of interest. JD states no conflicts of interest. JM states no conflicts of interest. JW states no conflicts of interest. CB states no conflicts of interest. HE states no conflicts of interest. KMK states no conflicts of interest. KW states no conflicts of interest. LR states no conflicts of interest.

Figures

Fig. 1
Fig. 1. Response, progression-free, and overall survival of EMD patients treated with ide-cel, cilta-cel, talquetamab, or teclistamab.
A Visual representation of response patterns in regard to therapy. B PFS (serologic and EMD combined). C PFS (EMD only). D OS analysis by therapy.
Fig. 2
Fig. 2. Predictors of progression-free and overall survival after T-cell redirecting therapy.
A EMD PFS analysis by serologic response. B OS by serologic response. C EMD PFS by response to bridging.
Fig. 3
Fig. 3. EMD response by localization, and number of EMD lesions.
A Analysis of EMD response by localization. B Analysis of EMD response by number of lesions.
See this image and copyright information in PMC

References

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