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

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.