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Ibrutinib Plus Bendamustine and Rituximab Prolongs PFS in Older Patients with MCL
Ibrutinib added to bendamustine and rituximab followed by rituximab maintenance yields significantly longer progression-free survival (PFS) in older patients with previously untreated mantle cell lymphoma (MCL), according to findings from the phase 3 SHINE trial.
“Combination therapy with bendamustine and rituximab has become one of the most-used first-line regimens for [MCL], given evidence showing longer [PFS] with this combination than with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone),” wrote Michael Wang, MD, University of Texas MD Anderson Cancer Center, Houston, and colleagues.
The SHINE trial enrolled 523 patients who were randomized in a 1:1 ratio to receive ibrutinib with bendamustine plus rituximab and rituximab maintenance therapy (n = 261) or placebo with bendamustine plus rituximab and rituximab maintenance therapy (n = 262). The primary end point was investigator-assessed PFS. Secondary end points included overall survival (OS) and safety.
At a median follow-up of 84.7 months, the median PFS was 80.6 months in the ibrutinib group and 52.9 months in the placebo group (hazard ratio for disease progression or death, 0.75; 95% confidence interval, 0.59 to 0.96; P = .01). The percentage of patients with a complete response was 65.5% in the ibrutinib group and 57.6% in the placebo group (P = .06). OS was similar in the two groups.
Adverse events of grade 3 or 4 during the treatment period occurred in 81.5% of the patients in the ibrutinib group and in 77.3% of those in the placebo group. The most common grade 3 or 4 adverse events were neutropenia (in 47.1% of the patients in the ibrutinib group and in 48.1% of those in the placebo group), pneumonia (in 20.1% and 14.2%, respectively), lymphopenia (in 16.2% and 11.9%), anemia (in 15.4% and 8.8%), thrombocytopenia (in 12.7% and 13.1%), rash (in 12.0% and 1.9%), and leukopenia (in 10.0% and 11.2%).
Of the adverse events of clinical interest for BTK inhibitors, atrial fibrillation was reported in 13.9% of the patients in the ibrutinib group and in 6.5% of those in the placebo group; hypertension in 13.5% and 11.2%, respectively; diarrhea in 46.3% and 36.9%; major hemorrhage in 5.8% and 4.2%; and arthralgia in 17.4% and 16.9%. Adverse events during the treatment period were the primary cause of death in 28 patients (10.7%) in the ibrutinib group and in 16 (6.1%) in the placebo group.
In conclusion, “ibrutinib in combination with bendamustine plus rituximab and rituximab maintenance therapy was an effective first-line treatment in patients with [MCL] who were 65 years of age or older and were considered to be unsuitable candidates for autologous stem-cell transplantation,” the study authors wrote.
Source:
Wang ML, Jurczak W, Jerkeman M, et al. Ibrutinib plus Bendamustine and Rituximab in Untreated Mantle-Cell Lymphoma. N Eng J Med. 2022;386(26):2482-2494. Published online June 30, 2022. doi:10.1056/nejmoa2201817
