What Is the Current Role of Autologous Transplant in Mantle Cell Lymphoma?

Long-term follow-up from the phase 3 TRIANGLE trial (NCT02858258) showed that adding a Bruton tyrosine kinase (BTK) inhibitor to frontline chemoimmunotherapy for patients with mantle cell lymphoma (MCL) outperformed consolidative autologous stem cell transplantation (ASCT). Separately, the phase 3 EA4151 trial (NCT03267433) found that ASCT can be omitted without compromising survival in patients who reach undetectable minimal residual disease (MRD) after induction in MCL, according to Brad S. Kahl, MD.^1,2

“I feel now there are 2 ways to avoid the stem cell transplant. You could add the BTK inhibitor, or you could do the MRD assessment. If your MRD [is] undetectable, then subtract the stem cell transplant,” Kahl said in an exclusive interview with OncLive®.

At a median follow-up of 55 months, patients in the TRIANGLE trial who received ibrutinib (Imbruvica) without ASCT had a 4-year overall survival (OS) rate of 90% vs 81% for those who received chemoimmunotherapy plus ASCT alone (P = .0019).¹ In EA4151, 3-year OS among all patients (n = 516) was 82.7% with rituximab (Rituxan) maintenance alone compared with 82.1% with ASCT plus rituximab (HR, 1.11; 95% CI, 0.71-1.74; P = .66).²

In the interview, Kahl discussed TRIANGLE, EA4151, and other ongoing trials that are reshaping ASCT use in frontline MCL, along with open questions on induction intensity and treatment strategies for high-risk disease, which were presented at the 2026 Society of Hematologic Oncology Annual Meeting in September.

Kahl is a professor of medicine and director of the lymphoma program in the Division of Oncology at Washington University School of Medicine and Siteman Cancer Center in St Louis, Missouri.

OncLive: What is the current treatment landscape for MCL regarding transplants, and why is there debate about their ongoing role?

Kahl: For many years, standard therapy for MCL included a semi-intensive induction therapy followed by ASCT consolidation and then maintenance rituximab. The first year of treatment was difficult for patients, and it was a very prolonged treatment, but it did seem to result in improved outcomes. In the past 10 years or so, we’ve had the introduction of novel agents into MCL, and the European MCL Network conducted a large, important trial called TRIANGLE, in which they added the BTK inhibitor ibrutinib into a frontline treatment strategy. They not only added it to ASCT, but they also had an arm where they used it instead of stem cell transplant. Those results were presented at the American Society of Hematology Annual Meeting & Exposition a few years ago, have now been published, and even had some long-term follow-up [data] this year. What the trial shows clearly is that the 2 arms that had the BTK inhibitor added performed better than the arm that did not, and that was true for failure-free survival and now also OS. The arm in the study that had no transplant and the BTK inhibitor performed better than the arm that had the stem cell transplant. Common sense tells us that’s a much easier strategy for patients, since they don’t have to go through ASCT. The TRIANGLE study really put an end to ASCT in first-line management of MCL.

How does the potential for transplant currently factor into frontline treatment decision-making for MCL?

There’s really not any role for transplantation, at least ASCT, in the frontline management of MCL nowadays. We’re incorporating BTK inhibitors into the regimen, and for patients who have an inadequate response, we now have CAR [chimeric antigen receptor] T-cell therapy. I can’t remember the last time we did an ASCT in first-line MCL at our institution; it’s largely a dead issue.

What other trials have contributed to declining transplant use in MCL? What future regulatory developments could further reduce it?

The regulatory aspect to consideris if a patient was unable to access a BTK inhibitor to incorporate into the frontline strategy, then you might argue there’s still a role for ASCT. [However,], the US Cooperative Group system conducted an important clinical trial, [the EA4151 trial], where we also tested the need for ASCT. We used a different strategy [in this trial that] incorporated a MRD assessment at the end of therapy: if patients were MRD undetectable, proving they were in a deep, high-quality remission, we randomly assigned them to ASCT plus maintenance rituximab or to maintenance rituximab alone, without autologous stem cell transplant. Our trial showed that if you are MRD-negative, you really don’t benefit from the stem cell transplant.

Now there are 2 ways to avoid the stem cell transplant: you could add the BTK inhibitor, or you could do the MRD assessment, and if your MRD [is] undetectable, then subtract the stem cell transplant.

What key takeaways from the current state of transplantation in MCL are most important to know?

Now that the transplantation question is settled, what becomes interesting are the next questions. In the European TRIANGLE regimen, they still use high-dose cytarabine during the induction, and I question whether that’s necessary; there are some retrospective data suggesting it’s not.

We also conducted a US Cooperative Group trial called EA4181, which randomly assigned patients to different chemotherapy strategies with the inclusion of a BTK inhibitor, and these data suggest that if you add the BTK inhibitor to the induction, you don’t need the high-dose cytarabine. This is an ongoing question, but it’s starting to be addressed.

Other questions are: What to do with very high-risk MCL, like [TP53]-mutated disease, which tends not to respond well to chemotherapy? We now have some chemotherapy-free approaches using all targeted agents that seem to produce better outcomes, but these need to be studied further.

[Another question is:] Should these chemotherapy-free approaches, which look really good in high-risk disease, be tested in MCL? There is a US Cooperative Group trial about to initiate, [EA4251], that will test standard immunochemotherapy against a chemotherapy-free approach.

[Ultimately], what to do in high-risk disease, whether you need high-dose cytarabine, and whether chemotherapy-free regimens can replace chemotherapy [are current unanswered questions in MCL].

Editor’s Note: This transcript has been edited for grammar and clarity using artificial intelligence tools.

References

1. Dreyling M, Doorduijn J, Giné E, et al. Ibrutinib combined with immunochemotherapy with or without autologous stem-cell transplantation versus immunochemotherapy and autologous stem-cell transplantation in previously untreated patients with mantle cell lymphoma (TRIANGLE): a three-arm, randomised, open-label, phase 3 superiority trial of the European Mantle Cell Lymphoma Network. Lancet. 2024;403(10441):2293-2306. doi:10.1016/S0140-6736(24)00184-3
2. Fenske TS, Wang XV, Till BG, et al. Lack of benefit of autologous hematopoietic cell transplantation (auto-HCT) in mantle cell lymphoma (MCL) patients (pts) in first complete remission (CR) with undetectable minimal residual disease (uMRD): initial report from the ECOG-ACRIN EA4151 phase 3 randomized trial. Blood. 2024;144(suppl 2):LBA-6. doi:10.1182/blood-2024-212973