(OA-67) Phase 2 Study of Cevostamab Consolidation Following BCMA CAR T Cell Therapy: Preliminary Safety and Efficacy Data from the “STEM” (Sequential T Cell-Engagement for Myeloma) Trial
Associate Professor of Medicine Perelman School of Medicine, University of Pennsylvania Philadelphia, Pennsylvania
Introduction: BCMA-targeted CAR T cells have unprecedented activity in relapsed/refractory multiple myeloma (RRMM), but most patients (pts) relapse. FcRH5 is a MM antigen with expression independent of BCMA. Cevostamab (cevo) is an FcRH5-targeted, T cell-engaging bispecific antibody with activity in RRMM, including in pts with prior BCMA-directed therapies. We hypothesized that fixed-duration cevo following CAR T cells would be feasible, tolerable, and improve sustained MRD-negative complete response (CR) rates.
Methods: This is an ongoing single-institution, investigator-initiated study (NCT05801939). RRMM pts who received standard of care CAR T cells (ide-cel or cilta-cel), with stable disease or better, receive cevo starting 10-12 weeks (wks) post-CART at step-up dose of 3.6mg IV on Cycle 1 Day 1 (C1D1), followed by 132mg starting C1D8, then q3wks for total of 8 cycles. If pts have MRD-negative CR after C8 (Adaptive Clonoseq, at 10-5 sensitivity), they stop therapy and are observed. If not, they get another 8 cycles, then stop. Primary endpoint is frequency of MRD-negative CR 1 year post-CAR T cells. All patients receive prophylactic IVIG.
Results: 27 pts (20M and 7F; median age 64; 21 White, 6 Black) enrolled. 74% had high risk cytogenetics, with 41% having ≥2 high risk features; 19% had extramedullary disease. Median number of prior lines was 4 (2-10), with 74% triple-class refractory, 11% prior BCMA therapy, and 11% prior talquetamab. 93% received cilta-cel and 7% ide-cel. Reponses at enrollment were 63% CR/sCR, 15% VGPR, 18% PR, 4% SD; all 25 evaluable for MRD were MRD-negative. As of 6/27/25 data cut-off, no DLTs have been seen, including no ICANS or HLH; CRS was seen in 4 (15%) pts (3 G1, 1 G2) and infusion reactions in 19% (all G1/2). Median number of cycles is 8, and 6 (22%) pts had dose reductions to 90mg. Most common TEAEs are lymphopenia (74%, G3/4 67%), neutropenia (74%, G3/4 44%), cough (59%, G3/4 0%), rash 44% (G3/4 0%), thrombocytopenia 41% (G3/4 22%), upper respiratory infection 37% (G3/4 0%), and AST increase 33% (G3/4 7%). Infections were seen in 52% (G3/4 in 15%). Immune-related AEs were seen in 4 pts (colitis G1, neuropathy with ataxia G3, ITP G4, autoimmune hepatitis G1) – all resolved. So far, 22 pts are response-evaluable after 8 cycles, with 81% in sCR, 9% VGPR, 5% SD; 21/22 (95%) were MRD-negative at 10-5, and 20/22 (91%) at 10-6 (1 pt had PD after C4, counted as MRD+). 3 pts to date have required the 2nd 8 cycles of cevo. 14 pts are evaluable at 1 year post-CAR T cells, with 93% in MRD-negative (at 10-5) sCR, 79% at 10-6. With median follow-up of 12 months (range 3-25) post-CAR T cells, estimated 12-month PFS and OS are both 95%.
Conclusions: To date, cevostamab consolidation post-CAR T cell infusion appears feasible and well-tolerated in late-line RRMM, with low rates of non-hematologic G3/4 TEAEs, including infections. Preliminary efficacy appears promising, with over 90% showing sustained MRD-negative sCR at 1 year.
