Chemoimmunotherapy With Ibrutinib Shows Improved Survival Over Standard of Care in Mantle Cell Lymphoma
Ibrutinib plus bendamustine-rituximab and rituximab maintenance was found to lower the risk of disease progression or death by 25% compared with placebo in patients 65 years of age or older with newly diagnosed mantle cell lymphoma.
The combination of once-daily oral ibrutinib (Imbruvica; Janssen Pharmaceutical Companies of Johnson & Johnson) plus bendamustine-rituximab (BR) and rituximab maintenance was found to lower the risk of disease progression or death by 25% vs patients administered placebo plus BR and rituximab maintenance in patients 65 years of age or older with newly diagnosed mantle cell lymphoma (MCL).
These data, from the phase 3 SHINE study (Abstract #7502), are being presented in an oral session at the 2022 American Society of Clinical Oncology Annual Meeting, and were published in The New England Journal of Medicine. The SHINE study is among the largest clinical trials ever conducted in the first-line MCL setting and the first for a Bruton’s tyrosine kinase inhibitor (BTKi), according to the study investigators.
“There is an urgent need to improve outcomes for older patients with MCL,” said principal study investigator Michael L. Wang, MD, professor, Department of Lymphoma & Myeloma, The University of Texas MD Anderson Cancer Center, in a press release. “Given the median progression-free survival of 6.7 years, the ibrutinib combination demonstrated the potential to be a first-line treatment in this population.”
The phase 3 SHINE (MCL3002) study (NCT01776840) enrolled 523 patients 65 years of age or older with newly diagnosed MCL at 183 sites in 28 countries since 2013 and evaluated treatment with BR and rituximab maintenance plus either ibrutinib or the placebo. Approximately 65.6% of individuals had low or intermediate prognostic risk factors on the MCL international prognostic index (MIPI) and 8.6% had blastoid/pleimorphic histology.
Additionally, individuals included could not have received prior therapies for their disease. Investigators said the individuals were representative of the racial breakdown of individuals with newly diagnosed MCL and were mostly white.
Ibrutinib treatment was administered during induction and during rituximab maintenance for 2 years and continued indefinitely until disease progression or intolerance. Investigators reported that approximately 19.9% and 40.5% of individuals received subsequent anti-lymphoma therapy in the ibrutinib and placebo arms, respectively. Additionally, 38.7% received a second-line BTK inhibitor in the placebo arm.
The median progression-free survival PFS, which was the study’s primary endpoint, was 80.6 months with ibrutinib compared to 52.9 months in the control arm. The complete response rate was approximately 65.5% in the ibrutinib arm and approximately 57.6% in the placebo arm. The median overall survival (OS) had not been reached in either arm at the time of data cutoff.
Grade 3 or 4 treatment-related adverse events (AEs) occurred in 81.5% of individuals in the ibrutinib group and 77.3% in the placebo group. Further, investigators reported atrial fibrillation in 13.9% of individuals in the ibrutinib arm and 6.5% of individuals who received the placebo.
The safety profile was consistent with the known profile of the individual drug and individuals rated their health-related quality of life similarly across both treatment arms.
“This study shows that the ibrutinib combination significantly improved [PFS] with manageable toxicities,” Wang said in the statement. “I am encouraged that moving ibrutinib to the front-line setting will improve outcomes in these patients and should change the standard of care for elderly patients with [MCL].”
The individuals in the study continue to be followed to evaluate differences in OS between the treatment arms. Investigators said further research may evaluate chemotherapy-free or time-limited ibrutinib combinations.
Ibrutinib with chemoimmunotherapy improved progression-free survival for newly diagnosed mantle cell lymphoma patients. EurekAlert. News release. June 3, 2022. Accessed June 3, 2022. https://www.eurekalert.org/news-releases/954764