Researchers are reporting an impressive advance in the treatment of mantle cell lymphoma, a type of blood cancer that is considered incurable.
Patients who took the drug ibrutinib in addition to a standard treatment combination gained more than 2 years without disease progression or death compared with those receiving just the standard treatment.
“This appears to be a very promising treatment approach, especially in older patients based on this trial. The question is, can we extrapolate that to younger patients? And can we ultimately prove an overall survival benefit?” said Stephen Spurgeon, M.D., a co-author of the work. Spurgeon is an associate professor of medicine in the OHSU School of Medicine and director of the Lymphoma Program in the Knight Cancer Institute.
The New England Journal of Medicine published the results online today, coinciding with a presentation by first author Michael Wang, M.D., at the American Society of Clinical Oncology Annual Meeting in Chicago. OHSU was among the top enrollers of subjects among the 203 study sites.
Mantle cell lymphoma is most commonly diagnosed in older people and many are not candidates for aggressive chemo or stem cell transplantation. In older patients, treatment guidelines recommend less aggressive therapy, such as the combination of bendamustine and rituximab.
The randomized, double-blind, phase 3 SHINE study tested ibrutinib given in addition to bendamustine and rituximab. About 250 subjects received that combination and they were compared with a similar-sized group that got a placebo in addition to the two standard drugs.
Progression-free survival, that is, the time from random assignment in the trial to disease progression or death, was about 81 months in the ibrutinib group, versus 53 months in the placebo group. Overall survival was similar in both groups.
The benefit of adding ibrutinib came with the downside of added toxicities. The rate of serious adverse events was 82% in the ibrutinib group compared with 77% in the placebo group. Rates of infections, particularly pneumonia, were similar in the first 6 months, but were higher during the maintenance period in the ibrutinib group, the study authors noted. A few infections were fatal.
“Monitoring for toxicity will be important,” Spurgeon said. “But the toxicity is not so pronounced that the risks outweigh the benefits of a deeper, longer remission.”
The dramatic difference in progress-free survival was achieved even though most people in the ibrutinib group stopped taking the drug early, either because of an adverse event, disease progression or because they dropped out of the study. The median time on the drug was 24 months. Spurgeon said that suggests that continuous treatment with ibrutinib may not be necessary. Time-limited use of ibrutinib might work effectively but avoid toxicities and costs associated with continuous treatment.
“This will be a practice changing study,” he said. “We also still have a lot of work to do because, you know, these patients, despite the benefit, are still relapsing.”
Ibrutinib plus Bendamustine and Rituximab in Untreated Mantle-Cell Lymphoma by Michael L. Wang and others, New England Journal of Medicine (June 3, 2022)