This is a single-institution, single-arm, phase 2 study in which belantamab mafodotin (GSK2857916), an antibody-drug conjugate targeting B-cell maturation antigen (BCMA), will be administered to patients with multiple myeloma prior to and following high-dose melphalan and autologous stem cell transplantation (ASCT), in conjunction with standard lenalidomide maintenance.
This trial is currently open and accepting patients.
This is a single-institution, single-arm, phase 2 study in which belantamab mafodotin (GSK2857916), an antibody-drug conjugate targeting B-cell maturation antigen (BCMA), will be administered to patients with multiple myeloma prior to and following high-dose melphalan and autologous stem cell transplantation (ASCT), in conjunction with standard lenalidomide maintenance. We hypothesize that administration of belantamab mafodotin as part of autologous stem cell transplant consolidation and maintenance will be safe, well tolerated, and efficacious in comparison to historical data.
The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.
Inclusion Criteria:
Exclusion Criteria:
Phase 2
Enrollment: 47 patients (estimated)
View MoreDecember 08, 2024
Results: As of 7/1/24, 24 subjects (15 M and 9 F; median age 61 (range 37-72); 20 White, 4 Black) had received ≥1 dose of belamaf. R-ISS at diagnosis was stage 1 in 29%, 2 in 38%, 3 in 13%, and unknown in 21%. Fifteen (63%) had high risk cytogenetics, with 7 (29%) having ≥2 high risk features. One (4%) and 8 (33%) had extramedullary and paramedullary disease, respectively. Induction regimens were VRd in 29%, DaraVRd in 58% and other in 13%, with 67% receiving an anti-CD38 antibody. Responses at enrollment: 9 (38%) in PR and 15 (63%) in VGPR. The 1st 13 subjects started belamaf at 2.5 mg/kg; 8 had either their 2nd (D+60) or 3rd (D+150) dose skipped due to corneal toxicity, with 3 choosing to discontinue belamaf after 1 dose. After an amendment, subsequent subjects started at 1.9 mg/kg, with only 1 missed dose so far, and no discontinuations.
Of 17 subjects who have received at least 2 belamaf doses, 13 have required ≥1 dose reduction, with 7 having 2 dose reductions. Ocular toxicities were the most common treatment-emergent adverse events (TEAEs, n=22 with at least 1 follow-up visit post-belamaf), including keratopathy (100%, Gr 3 9%), blurred vision (91%, Gr 3 0%), decreased visual acuity (91%, Gr 3 41%), dry eye (68%, Gr 3 0%), photophobia and eye pain (32% each, Gr 3 0%). No grade 4 ocular toxicities were noted. Other common TEAEs included thrombocytopenia (45%, Gr 3/4 9%), upper respiratory infection (45%, Gr 3/4 0%), fatigue and leukopenia (36% each, Gr 3/4 0%), neutropenia, flu-like symptoms, and diarrhea (27% each, Gr 3/4 0%), myalgias (23%, Gr 3/4 0%), and increased ALT (23%, Gr 3/4 5%). Ten serious AE’s were seen in 7 subjects, including 1 grade 5 cardiac arrest D+132 post-ASCT in a patient with multiple cardiovascular co-morbidities, unrelated to study treatment. Belamaf had no apparent impact on stem cell collection (median 9.3x106 CD34+/kg in median 2 days) or post-ASCT engraftment (median time to ANC>1000 and platelets>50 of 11 and 15 days, respectively).
Seventeen subjects have reached the D+90 response assessment; all were able to start len maintenance, with 3 requiring dose reductions and none requiring len discontinuation. Best responses to date in these subjects are VGPR in 24% and sCR in 76%. At D+90, 14 were MRD-evaluable (2 had no baseline clone identified, 1 refused BM biopsy), with 9 (64%) MRD-neg at 10-5 and 8 (57%) at 10-6. At 12 months post-ASCT, 12 are MRD-evaluable (2 not yet at M12, 1 no baseline clone, 1 expired, 1 progressed), with 10 (83%) MRD-neg at 10-5 and 8 (67%) at 10-6. With median follow-up of 15.5 months (range 0.5 – 36), 1 patient has progressed at D+187, with 1-year PFS and OS estimates of 87% and 93%, respectively.
Conclusions: In newly-diagnosed MM patients with <CR after induction, belamaf every 3 months in conjunction with ASCT and len maintenance appears feasible (at 1.9 mg/kg starting dose), with expected reversible ocular toxicities, and so far has promising rates of sCR, MRD-negativity, and PFS. Accrual and follow-up are ongoing.
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Philadelphia, PA
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