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 in all cohorts. 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 (>91% in all cohorts). Response rates after CAR T cell infusion were significantly higher (93% with cilta-cel, 82% with ide-cel) than with bsABs (47% for talquetamab, 38% for teclistamab, p<0.0001). Complete resolution of EMD was more frequent after CAR T cell therapies (50% and 41%) than after bsABs (16% and 14%, p=0.001). At a median follow-up of 4.6 months, median PFS was not reached after cilta-cel and 11.2 months after ide-cel compared to talquetamab and teclistamab (3.2 and 2.8 months, p=0.03). Visceral and soft tissue manifestations responded significantly less frequent than EMD in other locations (p=0.02). With significantly higher response rates, deeper remissions and longer median PFS, CAR T cells may provide a meaningful benefit in EMD and should be considered preferentially.