From the Journals

Transplant provides no clear survival benefit in real-world MCL study



In younger patients with mantle cell lymphoma treated in U.S. community oncology settings in recent years, use of autologous transplant was not associated with improved survival, results of a large observational study show.

Autologous stem-cell transplant (ASCT) use was not linked overall survival (OS), according to the authors of the retrospective analysis of patients diagnosed with mantle cell lymphoma (MCL) between 2011 and 2021.

This lack of a clear survival benefit with use of ASCT is an “apparent contradiction” with prospective data from earlier clinical trials, authors wrote in the Journal of Clinical Oncology

However, they added, the finding is consistent with several recent registry analyses that also do not support a link between ASCT and overall survival in patients with MCL.

Although these findings are limited by the retrospective nature of the study, the results at least suggest that it is ethical to do research that doesn’t involve ASCT, study author Peter Martin, MD, said in an interview.

Furthermore, emerging data from the randomized TRIANGLE study from the European MCL Network suggest the potential for ASCT to be replaced by maintenance therapy with the Bruton's tyrosine kinase inhibitor ibrutinib, according to Dr. Martin, associate professor with Weill Cornell Medicine, New York.

“There are probably a lot of questions that will come up there, but essentially the barriers to research that do not include ASCT have been moved away, and we can go ahead and study non-ASCT (approaches) in younger patients,” Dr. Martin said.

No clear OS benefit

In current guidelines, recommended initial therapy for MCL patients younger than 65 years includes use of high-dose cytarabine-containing chemoimmunotherapy induction, followed by ASCT as consolidation, and then rituximab maintenance, Dr. Martin and coauthors say in their report.

Their primary analysis was based on the Flatiron Health database, which is derived from electronic medical records, mostly in U.S. community oncology practices, according to the report.

The researchers identified 1,274 patients under the age of 65 with a record of first-line treatment for MCL, and of those, 962 (or 76%) were considered eligible for ASCT.

Among ASCT-eligible patients, there was no significant association between receipt of ASCT and OS, with a hazard ratio of 0.86 (95% confidence interval, 0.63-1.18). The 3-year OS was 88% for patients receiving ASCT and similarly, 84% for those who did not, according to authors.

Likewise, there was no association between ASCT and real-world time to next treatment, an endpoint defined as time from start of first-line therapy to subsequent treatment or death, the report says.

Findings in perspective

The lack of clear survival benefit with ASCT in this and other recent observational studies may be explained in part by improvements in induction regimens, according to Timothy Fenske, MD, professor in the department of medicine at the Medical College of Wisconsin, Milwaukee.

“As our induction regimens have improved, it is very possible that the benefit for autologous transplantation will become less apparent,” Dr. Fenske said in an interview.

The discussion over ASCT in MCL is expected to evolve further in light of findings from TRIANGLE and EA4151, a randomized phase 3 trial of rituximab with or without ASCT specifically in patients with minimal residual disease (MRD)–negative MCL in first complete remission.

“If that study shows that the MRD-negative patients do not have much benefit from autologous transplantation,” Dr. Fenske said, “I think these studies will all be giving the same message – that autologous transplantation was beneficial back when induction regimens were poor (for example, CHOP without rituximab), but will have much less benefit in patients receiving modern inductions, which by and large will get more patients to be MRD negative.”

However, subgroup analyses of those TRIANGLE will be important, he added, since some patients may still benefit from ASCT, such as younger patients who remain MRD positive, or who have certain other high-risk molecular features.

Dr. Martin reported consulting or advisory roles with Janssen, BeiGene, Karyopharm Therapeutics, Kite/Gilead, Verastem, ADC Therapeutics, Bristol Myers Squibb/Celgene, Epizyme, Merck, MorphoSys, and Takeda. He reported institutional research funding from Karyopharm Therapeutics.

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