Michael L. Wang, MD, Professor, Department of Lymphoma & Myeloma at the University of Texas MD Anderson Cancer Center, discusses results of the phase 3 SHINE study which evaluated the safety and efficacy of ibrutinib in combination with bendamustine and rituximab in patients 65 years of age or older with newly diagnosed mantle cell lymphoma. These data were recently presented at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting and were published in The New England Journal of Medicine.
Mantle cell lymphoma is a rare form of non-Hodgkin’s lymphoma in which B-cells become cancerous and form tumors in the lymph nodes that can quickly spread to other regions. It commonly affects people over the age of 65 who typically cannot tolerate intensive chemoimmunotherapy and stem cell transplantation, resulting in poor clinical outcomes.
As Dr. Wang explains, the SHINE study enrolled 523 patients 65 years of age or older with newly diagnosed mantle cell lymphoma. All participants were randomly assigned to receive 560 mg ibrutinib QD or placebo in combination with bendamustine and rituximab for a maximum of six 28-day cycles. Participants with a complete response or partial response continued to receive maintenance therapy with rituximab every second cycle for a maximum of 12 additional doses. Ibrutinib or placebo was administered daily until progressive disease or unacceptable toxicity.
The study met its primary endpoint of progression-free survival. With a median follow-up of 84.7 months, the ibrutinib plus bendamustine and rituximab, and rituximab maintenance combination showed a statistically significant and clinically meaningful 2.3 year improvement in median progression-free survival. Median progression-free survival in the ibrutinib arm was 6.7 years compared to 4.4 years in the placebo arm (stratified hazard ratio [HR]: 0.75, 95 percent confidence interval [CI], 0.59-0.96; p = 0.011).
Key secondary endpoints included complete response, time-to-next treatment, overall survival, and overall response rate. A complete response was achieved in 171 patients (65.5%) in the ibrutinib arm and 151 patients (57.6%) in the placebo arm (p = 0.057). The rates of objective response were similar between the two arms (ibrutinib: 89.7%; placebo: 88.5%). Median time-to-next treatment was not reached in the ibrutinib arm and was 92 months in the placebo arm (HR: 0.48, 95 percent CI, 0.34-0.66). Overall survival was similar between treatment arms and median overall survival was not reached in either treatment arm (HR: 1.07, 95 percent CI, 0.81-1.40).
The safety profile of the ibrutinib plus bendamustine and rituximab regimen was consistent with known safety profiles of ibrutinib as well as bendamustine and rituximab. Across all treated patients, the most common Grade 3/4 adverse events were neutropenia, pneumonia, anemia, thrombocytopenia, rash, and diarrhea. Treatment-emergent adverse events of clinical interest included atrial fibrillation which was reported in 13.9% of patients in the ibrutinib arm and 6.5% in the placebo arm; hypertension in 13.5% and 11.2%; major bleeding in 5.8% and 4.2%; any bleeding 42.9% and 21.5%; and arthralgia in 17.4% and 16.9%, respectively.
Dr. Wang also presented 3-year follow-up data from the ZUMA-2 trial which evaluated the efficacy of brexucabtagene autoleucel (KTE-X19) in participants with relapsed/refractory mantle cell lymphoma. Previous 1-year data demonstrated a 93% objective response rate and 67% complete response rate in patients with relapsed/refractory mantle cell lymphoma who received brexucabtagene autoleucel. The 3-year data demonstrated an objective response rate of 91% and complete response rate of 68%. No new safety signals were observed. Overall, this data suggests the long-term safety and efficacy of brexucabtagene autoleucel in patients with relapsed/refractory mantle cell lymphoma.
To learn more about mantle cell lymphoma and other rare cancers, visit checkrare.com/diseases/cancers/
