Bispecific antibody therapy in central nervous system (CNS) multiple myeloma (MM): Multicenter retrospective study.

Abstract

e19505 Background: CNS involvement in MM is a rare, aggressive extramedullary manifestation with a poor prognosis (~4 months). The blood-brain barrier limits the effectiveness of cytotoxic drugs and novel therapies. Patients (pts) with CNS-MM are often excluded from clinical trials, leading to limited data on its incidence, prognosis, and optimal treatment. While bispecific antibodies (BsAbs) have revolutionized treatment for relapsed/refractory (R/R) MM, their effectiveness in CNS-MM remains uncertain due to the exclusion of these patients from key trials. Methods: This multicenter, retrospective study included 8 patients with CNS-MM who were treated with BsAbs across 3 academic medical centers in the U.S. All patients received at least one full dose after step-up dosing (SUD). Clinical characteristics and outcomes were collected and analyzed. Results: Of the 8 patients, 7 received talquetamab and 1 received teclistamab. The median age at diagnosis was 66 years (range 48-73), and 6 patients (75%) were male. Cytogenetic findings included 1q21 amplification in 6 patients (75%) and 17p deletion in 3 patients (37.5%). No patients had t(11;14), t(4;14), t(14;16), or t(14;20). CNS involvement included intraparenchymal plasmacytoma (37.5%), leptomeningeal disease (25%), or both (37.5%). Fifty percent had extramedullary disease outside of CNS-MM, with 2 patients (25%) having plasma cell leukemia and 1 patient having R-ISS Stage III disease. Most patients (87.5%) were penta-refractory at the time of BsAb initiation with 37.5% of patients having received prior CAR-T. Among the 6 evaluable patients, 100% achieved a CNS response, with a median time to best response of 10 weeks (median 6.5 doses). All patients with measurable systemic disease (n=6) had a systemic response of ≥ VGPR. CNS-directed therapies, such as radiation (RT) or intrathecal chemotherapy (IT), were used in 7 patients (87.5%). No cases of grade ≥ 3 cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) were observed. Two patients were unable to have recorded CNS responses due to hospice enrollment or death. Conclusions: BsAbs show promise as a feasible and effective treatment for CNS-MM patients, offering good CNS disease control without an increased risk of CRS or ICANS. These findings underscore the potential of BsAbs in managing this high-risk population and support the need for further investigation.