Novel first-line treatment option for mantle cell lymphoma 

Bendamustine-rituximab chemotherapy plus ibrutinib outperformed bendamustine-rituximab alone as a first-line treatment for older patients with mantle cell lymphoma. The phase 3 SHINE trial demonstrated a meaningful benefit of the combination therapy over the monotherapy in terms of progression-free survival (PFS) but not in overall survival (OS). Nonetheless, bendamustine-rituximab plus ibrutinib displayed itself as a highly effective option for the mantle cell lymphoma population. 

Bendamustine-rituximab has become the most commonly used first-line regimen for older patients with mantle cell lymphoma [1]. The Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib has transformed the care of patients with relapsed/refractory mantle cell lymphoma [2]. The phase 3 SHINE trial (NCT01776840), presented by Prof. Michael Wang (Anderson Cancer Center, TX, USA), randomised 523 older patients (≥65 years) with untreated mantle cell lymphoma 1:1 to 6 cycles of bendamustine-rituximab plus ibrutinib and rituximab maintenance therapy or bendamustine-rituximab plus placebo and rituximab maintenance therapy [3]. The primary endpoint was PFS.

After a median follow-up duration of 7.1 years, the PFS was significantly higher in the ibrutinib arm than in the placebo arm (6.7 vs 4.4 years; HR 0.75; P=0.011; see Figure), representing a 25% reduction in risk of disease progression or death in the combination therapy arm. The results were mostly consistent across subgroups, with the exception of high-risk patients, in whom the PFS results were comparable (HR 1.02). Notably, the OS appeared not to differ between the experimental arm and the placebo arm, with 55% and 57% survival after 84 months, respectively. However, the OS results were not yet mature at the time of the presentation.

Figure: Progression-free survival of ibrutinib versus placebo in addition to bendamustine-rituximab [3]



PFS, progression-free survival; BR, bendamustine-rituximab.

Neutropenia was the most common adverse event, occurring in approximately 50% of the patients in each arm. Rash and pneumonia were more common in the experimental arm, as well as atrial fibrillation (13.9% vs 6.5%), and bleeding of any grade (42.9% vs 21.5%). However, the rate of major bleedings was comparable (5.8% vs 4.2%).

Prof. Kerry Savage (University of British Columbia, Canada), discussant of this trial, argued that the results of the SHINE trial support bendamustine-rituximab plus ibrutinib as a first-line treatment option for older or transplant-ineligible patients with mantle cell lymphoma, especially for those who display a good performance status. “Careful selection of patients is still needed, since the safety analysis showed increased rates of neutropenia, infections, and cardiac complications in the combination arm. Finally, mantle cell lymphoma is clinically and biologically diverse and we need to implement the use of BTK inhibitors in personalised approaches for our patients.”

1. Martin P, et al. J Clin Oncol. 2021;(39):7504–7504. 
2. Wang ML, et al. N Engl J Med. 2013;369:507–516. 
3. Wang ML, et al. Primary Results From the Double-Blind, Placebo-Controlled, Phase III SHINE Study of Ibrutinib In Combination WithBendamustine-Rituximab and Rituximab Maintenance as a First-Line Treatment for Older Patients With Mantle Cell Lymphoma. LBA 7502, ASCO 2022 Annual Meeting, 3–7 June, Chicago, IL, USA.

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Posted on 5 August 20226 September 2023