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Ibrutinib in combination with bendamustine and rituximab with rituximab maintenance elicited a significant improvement in progression-free survival compared with standard chemoimmunotherapy in older patients with mantle cell lymphoma.
Ibrutinib (Imbruvica) in combination with bendamustine (Bendeka) and rituximab (Rituxan) with rituximab maintenance elicited a significant improvement in progression-free survival (PFS) compared with standard chemoimmunotherapy in older patients with mantle cell lymphoma (MCL), according to primary results from the phase 3 SHINE trial (NCT01776840), presented during the 2022 ASCO Annual Meeting.1
At a median follow-up of 84.7 months, the median PFS among patients who received the ibrutinib-based regimen (n = 261) was 6.7 years (80.6 months), compared with 4.4 years (52.9 months) among patients in the placebo arm (n = 262; HR, 0.75; one-sided P = .011).
Michael Wang, MD, lead study author and professor in the Department of Lymphoma and Myeloma at 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. “[With] 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 do not 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 represents an “urgent unmet need.”
Wang and colleagues compared ibrutinib administered at 560 mg orally daily in combination with bendamustine/rituximab (90 mg/m2 and 375 mg/m2, respectively), with placebo plus bendamustine/rituximab in patients aged 65 years or older. The median age was 71 years (range, 65-87).
Additional results demonstrated a complete response rate of 65.5% in the ibrutinib arm vs 57.6% in the placebo arm (P = .0567). However, there was no statistical significance in OS between the 2 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 AEs 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