At the 65th American Society of Hematology (ASH) Annual Meeting in San Diego, California, Charalambos Andreadis, MD, Helen Diller Family Comprehensive Cancer Center, UCSF, San Francisco, California, presented on a randomized phase 3 clinical trial to evaluate the addition of ibrutinib to autologous hematopoietic stem cell (autoHCT) as part of conditioning and as consolidation therapy for patients with high-risk relapsed/refractory (R/R) activated-B-Cell subtype diffuse large B-cell lymphoma (ABC-DLBCL.)

The primary analysis demonstrated that ibrutinib with and following autoHCT for patients with relapsed/refractory ABC-DLBCL was well-tolerated, and may improve progression-free survival. 

Transcript:

I'm Babis Andreadis. I'm a professor at the University of California in San Francisco, and I specialize in lymphoma and cell therapies. The study I presented today is a randomized phase 3 study of ibrutinib with and following autologous stem cell transplant for patients with relapsed lymphoma of the ABC subtype. This is a relatively common subtype of diffuse large B-cell lymphoma, and there's good evidence to suggest that it's overrepresented at the time of relapse or progression. Up until a few years ago, we didn't really have more effective therapies for lymphoma that's relapsed. Now, we have CAR T-cells, we have bispecific antibodies, but at that point, transplant was the only way to go. The study attempted to use some molecular biology insights into incorporating novel therapies in that setting, and the drug that we chose was ibrutinib, because it has activity in this disease, but also, has an immunomodulatory effect that can be helpful.

The study took many years, unfortunately, to accrue, because the methodology that we used to enroll patients was difficult to do in a large group setting. Having said that, we did accrue a significant number of patients that we can learn from. I think what we learned, first and foremost, was that it's safe to combine with a transplant, and it's safe to use as a maintenance therapy in this patient population. We did not see any unforeseen toxicity, and it was well tolerated. At the end of the day, we think that it may have shown a benefit in terms of progression-free survival. It's just that the study didn't reach its full accrual, so the results were not statistically significant. But there was clearly a lower rate of progressions on the ibrutinib arm. Going forward, I think ibrutinib should be considered in the setting of autologous stem cell transplant, but also, in the setting of more modern therapies, like CAR T-cell or bispecific antibodies, because it can provide a significant effect in this patient population.

Source:

Andreadis C, Bobek O, Hsi ED, et al. Ibrutinib Added to Standard Conditioning a Consolidation Therapy Following Autologous Hematopoietic Stem Cell Transplantation (AutoHCT) for Relapsed/Refractory Activated-B-Cell Subtype Diffuse Large B-Cell Lymphoma (ABC-DLBCL): Primary Analysis of the US Intergroup Double-Blind Randomized Phase III Study Alliance A051301/BMT-CTN 1201. Presented at the ASH 65th Annual Meeting & Exposition; December 9-12 2023; San Diego, California. Abstract 437