Taiga Nishihori, MD, Associate Member, Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida, shares the results of a phase 2 trial of ixazomib maintenance therapy after allogeneic hematopoietic cell transplant (alloHCT) in patients with high-risk multiple myeloma (MM), the data of which are being presented at the virtual 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

Transcript

Hi, I'm Taiga Nishihori from Moffitt Cancer Center, Department of Blood and Marrow Transplant and Cellular Immunotherapy. I'm an associate member.

Multiple myeloma that is high risk has very limited survival. There was a prior clinical trial done by BMT CTN called 0102 that compared tandem autologous transplant and tandem auto-allo transplant from an HLA-matched donor. It showed improved progression survival for high-risk myeloma patients.

We're building on prior trial. The data that was emerging at the time was the feasibility of combination of bortezomib to fludarabine/melphalan conditioning and some toxicity concerns from immunomodulatory agent used as a maintenance therapy.

We designed the trial by using a combination of bortezomib and melphalan/fludarabine and using ixazomib, which is a proteasome inhibitor, for maintenance therapy.

This was an allogeneic transplant trial for high-risk multiple myeloma patients who had HLA-matched donor, either related or unrelated. We took them to allogeneic transplant with fludarabine/melphalan/bortezomib. About two to three months after transplant, we randomized them to ixazomib versus placebo. The plan was to continue maintenance therapy for 12 cycles.

This study, unfortunately, was put on hold after early signals for toxicity. We modified our protocol by removing post-transplant bortezomib and continued the treatment. After the hold was lifted, we enrolled about 40 patients in addition, and we did a trial.

The trial was closed early before we met the accrual goal. It was an underpowered study. In general, the outcomes, looking at PFS and OS, were similar between ixazomib and placebo. We did not see any difference between the two.

People were able to complete maintenance therapy, in general. What we can say from the study is that this particular intervention did not cause additional either positive or negative impact.

The allogeneic transplantation for multiple myeloma remains investigational. I would say that use of this particular modality still would be best done in a well-designed clinical trial.

Having said that, our platform of melphalan, fludarabine, and bortezomib, without using post-transplant bortezomib, was rather safe. If we look at all our populations who had a transplant, overall survival of two years was 80 percent. Transplant-related mortality was around 11 percent for the entire cohort.

It was about 8.7 percent at two years for those patients who had transplant without post-transplant bortezomib. The platform could work, although with emerging and numerous therapeutic options for multiple myeloma patients, this would likely not be done on off-study basis.

We do think this platform is rather safe. It is possible that we may consider using this allogeneic transplant platform in patients who may have already experienced relapse from other therapies. For example, a CAR T cell therapy is an emerging valuable option, so patients who had CAR T and failing CAR T. A question that we may pose is would allogeneic transplantation be utilized in a particular setting like that.

In addition, there are resource-limited geographic areas where CAR T may not be available. Would the transplant be useful in those patient populations? That's another question.

It is a phase II study designed to look at the impact of post-allo-transplant maintenance. It was unfortunate that we were not able to address that question directly because of the limited enrollment. If there are any future opportunities to ask this question, I think people are interested in knowing that.