A recent phase 2 trial showed that in patients with high-risk multiple myeloma (MM) undergoing allogeneic hematopoietic cell transplantation (HCT), reduced-intensity conditioning (RIC) with fludarabine/melphalan/bortezomib (Flu/Mel/Bort) was feasible. However, the primary endpoint of the study was considered unable to be fully assessed. The study results were published in the journal Transplantation and Cellular Therapy.
The trial ended early due to enrollment challenges, therefore a full assessment of ixazomib maintenance efficacy could not be completed, the study investigators explained in their report. The use of maintenance therapy following allogeneic HCT in MM had not been established, but the researchers hypothesized it could potentially reduce relapse risk.
The study was the phase 2, double-blind, prospective, multicenter BMT CTN 1302 trial (ClinicalTrials.gov Identifier: NCT02440464). The trial enrolled patients with high-risk MM, which involved features such as poor-risk cytogenetics, plasma cell leukemia, or a relapse within 24 months following autologous HCT.
Patients were randomized into either of 2 maintenance therapy arms following allogeneic HCT, with 1 arm receiving ixazomib and the other arm receiving placebo. Patients were given Flu/Mel/Bort RIC and graft-versus-host disease (GVHD) prophylaxis with tacrolimus plus methotrexate. The primary end point of the study was progression-free survival (PFS), and there were several secondary end points.
There were 57 patients enrolled in the trial, of whom 52 (91.2%) underwent allogeneic HCT. The median patient age was 56.0 years (range, 35.3-65.3). The total randomized population included 43 patients, 21 of whom were in the ixazomib treatment arm and 22 were in the placebo arm.
At 21 months following randomization, PFS rates were reportedly similar between treatment arms. The 21-month cumulative incidence of progression after randomization was 44.7% (90% CI, 25.6-62.1%) for patients in the ixazomib arm, and it was 36.4% (90% CI 19.8-53.3%) for patients in the placebo arm (P =1.00). Estimated 21-month postrandomization overall survival rates were reported to be 94.7% in the ixazomib arm and 86.4% in the placebo arm (P =.17). Nonrelapse mortality rates were also similar between arms.
Grade 3 or 4 acute GVHD at 100 days postrandomization occurred with cumulative incidences of 9.5% in the ixazomib arm and 0% in the placebo arm (P =1.00). For chronic GVHD, the estimated cumulative incidences at both 12 months and 21 months postrandomization were 68.6% in the ixazomib arm and 63.6% in the placebo arm (P =1.00).
Although the early study closure impacted efficacy assessments, the researchers were able to make other observations. For example, the Flu/Mel/Bort RIC regimen appeared to be feasible in this study. “In summary, the Flu/Mel/Bort RIC regimen with tacrolimus/methotrexate GVHD prophylaxis can be a good platform for allografting in myeloma patients,” the study investigators concluded.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Bashir Q, Nishihori T, Pasquini MC, et al. Multicenter phase II, double-blind placebo-controlled trial of maintenance ixazomib after allogeneic transplantation for high-risk multiple myeloma: results of the BMT CTN 1302 trial. Transplant Cell Ther. Accepted manuscript. Published online July 12, 2022. doi:10.1016/j.jtct.2022.07.007