Primary results from the Phase III SHINE study demonstrated that once-daily oral Imbruvica plus bendamustine-rituximab (BR) and rituximab maintenance significantly reduced the risk of disease progression in Mantle Cell Lymphoma.- Janssen Biotech

This study is one of the largest clinical trials ever conducted in first-line MCL and the first for a Bruton’s tyrosine kinase inhibitor (BTKi). The data were presented in an oral session and featured in a press briefing during the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, and were published in The New England Journal of Medicine. The data will also be presented as an oral presentation at the 2022 European Hematology Association (EHA) Annual Congress.

The Phase III SHINE (MCL3002) study (NCT01776840) – sponsored by Janssen Biotech, Inc., in collaboration with Pharmacyclics LLC, an AbbVie Company – enrolled 523 patients aged 65 years or older with newly diagnosed MCL. All participants were randomly assigned to receive Imbruvica (560 mg orally daily until progression or unacceptable toxicities) or placebo plus BR for a maximum of six 28-day cycles; participants with a complete response (CR) or partial response (PR) continued to receive maintenance therapy with rituximab every second cycle for a maximum of 12 additional doses. Imbruvica or placebo was administered daily until progressive disease or unacceptable toxicity.

The SHINE study met its primary endpoint of progression-free survival (PFS) . Key findings from the Phase III SHINE study include: i. With a median follow-up of 84.7 months, the Imbruvica plus BR and rituximab maintenance combination showed a statistically significant and clinically meaningful 2.3-year improvement in median PFS. ii Median PFS in the Imbruvica plus BR arm was 6.7 years compared to 4.4 years in the placebo plus BR arm (stratified hazard ratio [HR]: 0.75, 95 percent confidence interval [CI], 0.59-0.96; p = 0.011).

Key secondary endpoints included : CR, time-to-next treatment (TTNT), overall survival (OS), and overall response rate (ORR). i. A CR was achieved in 171 patients (65.5 percent) in the Imbruvica plus BR arm and 151 patients (57.6 percent) in the placebo arm (p = 0.057). The rates of objective response were similar between the two arms (Imbruvica plus BR: 89.7 percent; placebo: 88.5 percent). ii Median TTNT was not reached in the Imbruvica plus BR arm. The median TTNT was 92 months in the placebo plus BR arm (HR: 0.48, 95 percent CI, 0.34-0.66).111. iii. OS was similar between treatment arms and median OS was not reached in either treatment arm (HR: 1.07, 95 percent CI, 0.81-1.40).

The safety profile of the Imbruvica plus BR regimen was consistent with known safety profiles of Imbruvica as well as BR. Across all treated patients, the most common Grade 3/4 Adverse Events (AEs) greater than 5 percent were neutropenia (Imbruvica plus BR: 47.1 percent; BR: 48.1 percent), pneumonia (Imbruvica plus BR: 20.1 percent; BR:14.2 percent), anemia (Imbruvica plus BR: 15.4 percent; BR: 8.8 percent), thrombocytopenia (Imbruvica plus BR: 12.7 percent; BR: 13.1 percent), rash (Imbruvica plus BR: 12 percent; BR: 1.9 percent), and diarrhea (Imbruvica plus BR: 6.9 percent; BR: 3.8 percent). Treatment-emergent AEs of clinical interest with BTKis included atrial fibrillation (AF) which was reported in 13.9 percent of patients in the Imbruvica plus BR arm and 6.5 percent in the placebo arm; hypertension in 13.5 percent and 11.2 percent; major bleeding in 5.8 percent and 4.2 percent; any bleeding 42.9 percent and 21.5 percent; and arthralgia in 17.4 percent and 16.9 percent, respectively.

Imbruvica is currently approved globally for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. Within the U.S., this indication is approved under accelerated approval based on overall response rate (ORR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

See- "Ibrutinib plus Bendamustine and Rituximab in Untreated Mantle-Cell Lymphoma." Michael L. Wang, M.D., Wojciech Jurczak, M.D., Ph.D., Mats Jerkeman, M.D., Ph.D., et al., for the SHINE Investigators-June 3, 2022. DOI: 10.1056/NEJMoa2201817.