In a recent trial of the European MCL Network, people with mantle cell lymphoma who received the Bruton’s tyrosine kinase inhibitor ibrutinib had rates of progression-free survival and overall survival that were on par with the current standard of care (high-dose immunochemotherapy followed by autologous stem cell transplantation), regardless of whether the patients received a stem cell transplant in addition to ibrutinib. Researchers are still awaiting data from a third comparison—between patients receiving ibrutinib plus a transplant or ibrutinib without a transplant—but say the available findings support ibrutinib over the previous standard of care. These findings were presented at the 2022 American Society of Hematology (ASH) Annual Meeting and Exposition by Martin Dreyling, MD, PhD, and colleagues (Abstract 1).
Martin Dreyling, MD, PhD
“Based on our findings, standard chemotherapy plus ibrutinib (with or without autologous stem cell transplantation) is the new [first-line] standard of care for patients [with mantle cell lymphoma],” said Dr. Dreyling, of LMU University Hospital Munich in Germany. “We have to wait for the full results; so far, we don’t see any difference between these two ibrutinib curves for progression-free survival and overall survival, but already both curves are numerically superior to the old standard, autologous transplant only. I think clinicians will interpret these results as suggesting you may essentially substitute autologous transplant with ibrutinib to avoid its well-known long-term toxicities.”
Study Details
The trial enrolled 870 younger adult patients (median age = 57 years) treated for mantle cell lymphoma in 14 countries, primarily in Europe. One-third of the participants were assigned to receive standard care (high-dose cytarabine-containing immunochemotherapy followed by autologous stem cell transplantation and rituximab maintenance if this is the clinical routine), one-third received standard care plus ibrutinib, and one-third received ibrutinib without a stem cell transplant. Researchers tracked outcomes for a median of 2.5 years.
Key Results
The primary endpoint, failure-free survival, was defined as survival without stable disease or disease progression at the end of the initial course of treatment. By this measure, the standard of care was not found to be superior to ibrutinib without a stem cell transplant, and the standard of care plus ibrutinib was found to be superior to the standard of care alone.
In the maintenance phase of treatment, patients who received the standard of care plus ibrutinib had higher rates of adverse events than did patients who received either the standard of care or ibrutinib alone. Combined with findings from other trials, these results suggest ibrutinib may be best used as a replacement for—rather than an augmentation to—stem cell transplantation.
“Even from the perspective of toxicity, the ideal regimen is a combination of conventional chemotherapy plus ibrutinib,” said Dr. Dreyling.
In addition to continuing to collect and analyze data to compare the use of ibrutinib with and without stem cell transplantation, the researchers are investigating whether factors such as particular genetic mutations or the degree of cancer proliferation may influence the optimal treatment strategy.
Disclosure: For full disclosures of the study authors, visit ash.confex.com.
