Ibrutinib improves progression-free survival (PFS) when added to standard chemoimmunotherapy in older patients with previously untreated mantle cell lymphoma (MCL), according to results from the phase 3 SHINE trial presented at the 2022 ASCO Annual Meeting.1
Adding ibrutinib to standard treatment with bendamustine and rituximab improved the median PFS by 2.3 years and resulted in a 25% reduction in the risk of progression or death.
“SHINE is the first phase 3 study to show that ibrutinib in combination with chemoimmunotherapy is highly effective in patients with untreated MCL,” said study author Michael Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston.
“This study should set a new benchmark for first-line therapy in older patients with MCL or those unsuitable for stem cell transplantation,” he added.
The phase 3 trial (ClinicalTrials.gov Identifier: NCT01776840) included 523 patients with previously untreated MCL who were 65 years of age or older. The patients were randomly assigned to receive ibrutinib plus bendamustine-rituximab (261 patients) or placebo plus bendamustine-rituximab (262 patients).
All patients received 6 cycles of bendamustine (90 mg/m2 on days 1-2) and rituximab (375 mg/m2 on day 1). Ibrutinib was given at 560 mg daily until disease progression or unacceptable toxicity. Patients in either arm who achieved a response to induction could go on to receive rituximab maintenance every 8 weeks for up to 12 cycles.
At a median follow up of 84.7 months, the median PFS was 80.6 months with ibrutinib and 52.9 months with standard therapy alone (hazard ratio [HR], 0.75; 95% CI, 0.59-0.96; P =.011).
When looking at the PFS in years, the median PFS is 6.7 years with ibrutinib and 4.4 years with standard therapy, which is “a very meaningful benefit” with first-line treatment in this older population, Dr Wang said.
Ibrutinib prolonged the time to next treatment as well. The median time to next treatment was not reached in the ibrutinib arm and was 92.0 months in the standard arm (HR, 0.48; 95% CI, 0.34-0.66). The proportion of patients who received second-line therapy was 40.5% and 19.9%, respectively.
There was no significant difference in overall survival between the treatment arms, and the median overall survival was not reached in either arm (HR, 1.07; 95% CI, 0.81-1.40).
The most common treatment-emergent adverse events (TEAEs) in both arms were neutropenia, diarrhea, and nausea. Bleeding was more common in the ibrutinib arm than in the standard arm (42.9% vs 21.5%), as was atrial fibrillation (13.9% vs 6.5%).
TEAEs of interest that occurred at similar rates in the ibrutinib and standard therapy arms were major bleeding (5.8% vs 4.2%), hypertension (13.5% vs 11.2%), arthralgia (17.6% vs 16.9%), and secondary primary malignancies (21% vs 19%).
Dr Wang noted that these TEAEs are consistent with the known safety profiles of ibrutinib and bendamustine-rituximab.
These results were also published in The New England Journal of Medicine.2
Disclosures: This research was supported by Janssen Research & Development in collaboration with Pharmacyclics. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
- Wang M, Jurczak W, Jerkeman M, et al. Primary results from the double-blind, placebo-controlled, phase III SHINE study of ibrutinib in combination with bendamustine-rituximab (BR) and R maintenance as a first-line treatment for older patients with mantle cell lymphoma (MCL). Presented at ASCO 2022; June 3-7, 2022. Abstract LBA7502.
- Wang M, Jurczak W, Jerkeman M, et al. Ibrutinib plus bendamustine and rituximab in untreated mantle-cell lymphoma. N Engl J Med. Published online June 3, 2022. doi:10.1056/NEJMoa2201817