Ibrutinib combined with bendamustine and rituximab extended the highest progression-free survival rate ever reported for this patient population, in the phase 3 SHINE study.
In patients with newly diagnosed mantle cell lymphoma (MCL), the addition of ibrutinib (Imbruvica) to the standard-of-care treatment of bendamustine (Bendeka) and rituximab (Rituxan) significantly improved progression-free survival (PFS) by 2.3 years, which was a 50% improvement compared with placebo and standard of care, according to results of the phase 3 SHINE trial (NCT01776840).
Findings presented at the 2022 ASCO Annual Meeting demonstrated that at a median follow-up of 84.7 months, treatment with the ibrutinib-based regimen (n = 261) induced a median PFS of 6.7 years (80.6 months), compared with a median of 4.4 years (52.9 months) in the placebo-based arm (HR, 0.75; one-sided P =0.011).
Michael Wang, MD, lead study author and professor, department of lymphoma and myeloma, The University of Texas MD Anderson Cancer Center, noted that this is the first phase 3 clinical trial to demonstrate highly effective results with the combination of ibrutinib and chemoimmunotherapy.
“Indeed, this is very meaningful,” he explained during the presentation. “In this regimen we achieved 6.7 years without any disease. This is … a really remarkable achievement in the field of use for these patients.”
He noted it is also the highest PFS rate ever reported for this hard-to-treat population.
Some lymphoma treatments, such as intensive chemotherapy, targeted agents or transplantation are often unsuitable for the older MCL patient population. These treatments may be associated with the onset of severe adverse events (AEs) and older adults don’t typically respond well to them. However, this patient population is often underrepresented in clinical trials.
Wang noted that identifying an effective treatment for this patient population is an “urgent unmet need.”
Wang and colleagues compared ibrutinib (560 mg orally daily) in combination with bendamustine-rituximab (90 mg/m2; 375 mg/m2, respectively), to placebo plus bendamustine-rituximab in patients aged 65 years or older (median age, 71 years; range, 65-87).
Additional results demonstrated a complete response rate of 65.5% in the ibrutinib arm and 57.6% in the placebo arm (P = .0567). However, there was no statistical significance in overall survival between the two treatment arms (P = .648).
Time to next treatment was longer with ibrutinib than placebo (P <.001). And 52 (19.9%) patients on ibrutinib and 106 (40.5%) patients on placebo received subsequent anti-lymphoma therapies.
Grade 3 or 4 treatment-emergent AEs occurred in 81.5% and 77.3% of patients in the ibrutinib and placebo arms, respectively. Notably, atrial fibrillation was reported in 13.9% and 6.5% of patients in each arm, respectively. Other side effects noted by Wang included neutropenia, rash and pneumonia. Rates of major hemorrhage, hypertension, arthralgia and second primary malignancies were similar in both arms. Wang added that this safety profile was “no surprise” and was consistent with what has been reported in daily practice with ibrutinib.
“We believe this phase 3 clinical trial set a new benchmark for patients with a newly diagnosed (MCL) and the elderly and for those patients who are not eligible for autologous stem cell transplantation,” he concluded.
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). J Clin Oncol. 2022; 40(suppl_17):LBA7502. Doi: 10.1200/JCO.2022.40.17_suppl.LBA7502