BMT CTN 1902: Post-transplant Consolidation is Back, and This Time With CAR-T!

Overall, BMT CTN 0702 showed no improvement in outcomes with added post-ASCT consolidation as compared to standard lenalidomide maintenance.

For over 30 years, autologous stem cell transplantation (ASCT) has remained a key component of first-line treatment for multiple myeloma (MM). Many studies have investigated consolidation strategies to improve outcomes after ASCT, including the Phase 3 Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0702 STaMINA trial. Overall, BMT CTN 0702 showed no improvement in outcomes with added post-ASCT consolidation as compared to standard lenalidomide maintenance; however, in as-treated analyses, there was a potential benefit to tandem ASCT in patients with high-risk cytogenetics.

But what if we could choose tandem cellular therapies based on dynamic risk over time as opposed to static features at diagnosis — and that too, choose a novel ‘chaser’ therapy rather than just repeating the same high-dose melphalan again? Later today at the #Tandem25 meeting in Honolulu, we will get our first glimpse at how this approach might work. The BMT CTN 1902 trial will be presented by Dr. Alfred Garfall from the University of Pennsylvania as a late-breaking abstract, and it will be a session worth watching!

In brief, BMT CTN 1902 is a single-arm Phase 2 trial of chimeric antigen receptor T-cell (CAR-T) therapy in patients with MM who did not achieve a complete response (CR) following ASCT. Enrolled post-ASCT participants then underwent T-cell, idecabtagene vicleucel (ide-cel) CAR-T therapy, and lenalidomide maintenance thereafter. Without spoiling too much of Dr. Garfall’s presentation, CR rates improved dramatically after ide-cel with very few high-grade toxicities. Importantly, all 38 patients who received CAR-T therapy were able to resume lenalidomide a few months later.

The concept of CAR-T as a post-ASCT consolidation strategy in MM isn’t new, strictly speaking. KarMMa-2 Cohort C and CARTITUDE-2 Cohort D have investigated the same concept, as did KarMMa-9 before the study was terminated by the sponsor. There are a few key differences to keep in mind with BMT CTN 1902, however:

Participants in BMT CTN 1902 had not achieved a complete response despite 3+ months of post-ASCT lenalidomide maintenance (required per protocol), making their sub-CR response more likely to represent a truly melphalan-refractory clone.

Almost half of BMT CTN 1902 participants had been exposed to daratumumab-based induction, and almost a third had received doublet maintenance (generally for high-risk cytogenetics). This patient population thus reflects the current United States MM treatment landscape particularly well.

Resuming lenalidomide maintenance after ide-cel was a core component of BMT CTN 1902, in contrast to other studies of this topic where lenalidomide resumption was either optional or intentionally omitted for some patients. While lenalidomide resumption sometimes took as long as 5 months after CAR-T due to cytopenias or logistical delays, the authors have demonstrated that this approach — where ide-cel is supplementing rather than replacing standard post-ASCT maintenance — is practical.

We did reach out to Dr. Garfall to get his wisdom on where the future of CAR-T in this setting may lie. Over a quarter of BMT CTN 1902 participants had no measurable residual disease (MRD) going into CAR T-cell infusion, and perhaps sub-CR responses reflect slow paraprotein clearance. What’s next for CAR-T here? If ide-cel someday gains commercial approval for post-ASCT consolidation, will you recommend it to all patients or selectively based on disease features or response characteristics?

Dr. Garfall’s response: You are correct in noting that some of these patients were on the cusp of CR. Through some planned and ongoing correlative studies, we hope to gain more insight into which patients might benefit most from this approach. Ultimately, we would only want to subject patients to the risk, complexity, and cost of CAR T cell therapy if long-term benefit were demonstrated in a Phase 3 study. We view our results as a preliminary but still important step. Our study, along with those of other similar studies you’ve mentioned, shows that CAR T cells can be manufactured in the post-ASCT setting, that they expand in vivo and exert anti-MM activity even in the setting of low target antigen burden, and they seem to have a more favorable safety profile when used as consolidation compared to the relapsed setting. These are important findings that set the stage for Phase 3 studies of consolidation strategies.

To watch the full presentation, visit: https://vmx.m-anage.com/us/tandem2025/en-US/presentation/666867