Adding Ibrutinib to Standard of Care Improves Progression Free Survival in Older Patients with Mantle Cell Lymphoma
Mantle cell lymphoma is one of 70 subtypes of non-Hodgkin lymphoma. Relatively rare, it accounts for only 6% of all non-Hodgkin lymphoma cases. It gets its name because abnormal, malignant B cells usually develop in the part of the lymph nodes known as the mantle zone. Mantle cell lymphoma is an aggressive cancer that can spread quickly, meaning it is often diagnosed in the later stages.
Initial treatment approaches include combination chemotherapy and immunotherapy, followed by stem cell transplantation. The intensive course of treatment is well tolerated by younger patients. However, patients 65 or older are not candidates for this treatment due to risk of excessive toxicities. Instead, standard of care for this population includes chemotherapy bendamustine in combination with immunotherapy rituximab.
New data from the phase 3 SHINE trial suggests adding the Bruton’s tyrosine kinase inhibitor (BTKi) ibrutinib, a daily oral medication, to the standard of care regimen can improve patient free survival for older patients by 2.3 years. The results were presented at the 2022 American Society of Clinical Oncology Annual Meeting, as well as published in the New England Journal of Medicine.
SHINE data support bendamustine/rituximab & ibrutinib as a treatment option for #MCL in older pts unsuitable for intensive chemo or transplantation, but added toxicities a concern. https://t.co/lxJ1N5uBGY #ASCO22 #ASCODailyNews #HemOnc #lymsym @michaelwangmd
— ASCO (@ASCO) June 3, 2022
The trial included 532 patients, ages 65-87, with mantle cell lymphoma who were randomized into two arms:
- Ibrutinib combined with bendamustine and rituximab, followed by rituximab maintenance
- Bendamustine and rixtuximab plus placebo, followed by rituximab maintenance
The primary endpoint for the study was progression free survival, meaning the length of time from random assignment to disease progression or death. Patients in the ibrutinib arm had a median progression free survival of 6.7 years compared to 4.4 years in the placebo group. Trial investigators say the results are significant and should lead to a change in the standard of care, but Dr. Bijal Shah, a medical oncologist in Moffitt Cancer Center’s Malignant Hematology Department, says more data and research are needed.
“It is still too soon to say if this regimen will lead to a new standard of care for older patients with mantle cell lymphoma. I think a major challenge with the data presented relate to the need and benefit versus the toxicity of adding bendamustine. Notably, overall survival was not improved, and it suggests that a safe alternative is to deliver ibrutinib-based therapy at the time of relapse. It is hoped with future BTKi trials, we will learn more about the importance, or lack thereof, of the bendamustine component,” said Shah.
Overall survival, considered the gold standard for measuring the success of a clinical trial, is the time from treatment to death regardless of disease recurrence. In this trial, overall survival was similar in both arms of the study.
