Taiga Nishihori, MD from the H. Lee Moffitt Cancer Center & Research Institute speaks about the ASCO 2021 Abstract – The results of multicenter phase II, double-blind placebo-controlled trial of maintenance ixazomib after allogeneic hematopoietic cell transplantation (alloHCT) for high-risk multiple myeloma (MM) from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN 1302).
Link to Abstract:
https://meetinglibrary.asco.org/record/195823/abstract
Background information:
The function of alloHCT and subsequent maintenance in the treatment of high-risk MM remains unknown. To treat patients with high-risk MM, we tested the effectiveness of ixazomib maintenance treatment following alloHCT utilizing a reduced-intensity fludarabine/melphalan/bortezomib (Flu/Mel/Bort)-based conditioning regimen.
Methodologies:
Adults 70 years or younger with either high-risk MM characterized by cytogenetics or plasma cell leukemia (PCL) or recurrence within 24 months following autologous HCT were included in this phase 2 prospective multicenter study (NCT#02440464). Flu/Mel/Bort was the conditioning routine. Patients got HLA-matched donor peripheral blood transplants that had not been altered. Tacrolimus and methotrexate was used to prevent graft-versus-host disease (GVHD). Patients were randomly randomized (1:1) to receive ixazomib at 3 mg orally on days 1, 8, 15, and 28 on a 28-day cycle between days +60 and +120 after allogeneic HCT or a matched placebo for 12 cycles between days +60 and +120 after allogeneic HCT. The trial planned to enroll 138 patients, with 110 obtaining randomization for an ixazomib maintenance vs. placebo progression-free survival (PFS) comparison.
The following are the outcomes:
Fifty-seven patients were recruited from 15 sites between 2015 and 2018, with 52 (91.2%) receiving allogeneic HCT and 43 (82.7%) proceeding to randomization (21 assigned to ixazomib and 22 to placebo). A trial hold was placed on enrollment after 17 patients were enrolled due to toxicity concerns with the conditioning regimen. After an adjustment decreased bort to a single pre-HCT dosage, the remaining patients were recruited. As a result of these and other recruitment delays, the study was prematurely closed. The median age was 56 (range, 35-65), with 33 patients (57.9%) having high-risk MM and 9 patients (15.8%) having primary PCL. PFS and OS for all alloHCT recipients were 52 percent and 85 percent at 24 months, respectively, with a transplant-related mortality (TRM) of 11 percent. PFS (55.3 percent vs. 59.1 percent, p = 0.17), and OS (95 percent vs. 87 percent, p = 0.17), were similar in the ixazomib vs. placebo groups at 21 months post-randomization. At 100 days, the cumulative incidences of grade III-IV acute GVHD (9.5 percent vs. 0 percent) and chronic GVHD (69 percent versus 64 percent) were similar. At 21 months, the cumulative incidence of transplant-related mortality (TRM) for the ixazomib and placebo groups was 0.0 percent and 4.5 percent (90 percent CI: 0.5-16.5 percent), respectively.
Final Thoughts:
In severely high-risk individuals, alloHCT with lower intensity fludarabine/melphalan and a single pre-HCT dose of bortezomib is safe and can yield long-term disease control. Due to the early conclusion of the trial, ixazomib maintenance following alloHCT could not be studied as intended, although there was no evidence of an influence on outcomes.
Clinical trial information: NCT02440464 –
http://clinicaltrials.gov/show/NCT02440464