At the 2022 American Society of Hematology (ASH) Annual Meeting and Exposition in New Orleans, LA, Martin Dreyling, MD, LMU University Hospital Munich, Munich, Germany, presented data from the randomized Triangle trial on the efficacy and safety of ibrutinib combined with standard first-line treatment, or as a substitute for autologous hematopoietic stem cell transplantation (autoHSCT) in younger patients, at a median age of 57 years, with mantle cell lymphoma (MCL).

Transcript: 

My name is Martin Dreyling and I'm located in Munich, and I do have the privilege to coordinate the European [Mantle Cell Lymphoma] MCL network. Here in New Orleans at [the American Society of Hemotology] (ASH) [annual meeting], I had the privilege [of] doing the plenary session to give a final result of our study on first-line mantle cell lymphoma. I would say these [results] are really practice-changing. So what is the current standard of care in younger patients with mantle cell lymphoma? We established about 20 years ago that autologous transplant, or dose intensification in general, is the major principle of first-line treatment in younger patients. However, high-dose chemotherapy not only results in high efficacy, but also high toxicity, and therefore we try to move on. On the other hand, we do know that BTK inhibitors--Bruton's tyrosine kinase inhibitors--are the most potent therapeutic approach, at least in early relapses of mantle cell lymphoma.

That was why we came to the incorporation of this approach into first line. So what did we do? We compared the old standard, which is high-dose RSC-containing induction, followed by autologous transplant, and also by rituximab maintenance. [We] compared this one to an add-on arm, which means the same standard plus ibrutinib during induction and maintenance. The other experimental arm was a head-to-head comparison between autologous transplant and ibrutinib, essentially skipping the autologous transplant in the ibrutinib arm. So what are the results so far? This is a huge trial, [with] almost 900 patients being included. That allows us also to evaluate subgroups of patients. What we've seen concerning the add-on design may not be surprising: there was a significantly improved outcome with about 50% additional progression-free survival after 3 years.

What about the comparison of the hat-to-hat, autologous transplant versus ibrutinib? It came [as] a surprise to us. We speculated that autologous transplant still is superior, but this hypothesis was rejected and instead, the curves flipped around. In fact, the higher curve was the ibrutinib-containing arm, and the worst one was the old standard autonomous transplant. Again, there was a huge difference [of] about 15% after 3 years.

What about the third comparison, which is flipping around the question, if you take ibrutinib for granted, what about the addition of [an] autologous transplant? This is still an open question. I can't answer that, but so far the curves are totally overlapping and therefore we looked into toxicity. Here we see a clear increase of toxicity in the combined arm autologous transplant plus ibrutinib. To sum up, we could show that both ibrutinib arms did result in a clinically meaningful improvement of progression-free survival. I should also add that specifically for overall survival, again, both ibrutinib arms were superior to the old standard. What about toxicity? Toxicity definitely favors ibrutinib only in comparison to the combined ibrutinib plus autologous transplant arm.

In my opinion, this is really changing our standard of care, leading to a more efficient treatment with less toxicity. I think, and I'm not the only one, [that] this is really finalizing, let's say, the life cycle of autologous transplant. Of course, this is not the achievement of single [people], but really of the whole consortium. This large international trial, a pure academic trial, had been performed in 14 different countries.
 

Source:

Dreyling M, Doorduijn JK, Gine E, et al. Efficacy and Safety of Ibrutinib Combined with Standard First-Line Treatment or As Substitute for Autologous Stem Cell Transplantation in Younger Patients with Mantle Cell Lymphoma: Results from the Randomized Triangle Trial By the European MCL Network. Presented at the 2022 ASH Annual Meeting & Exposition; December 10-13, 2022; New Orleans, LA. Abstract 1.