Ibrutinib Combined with Standard Chemoimmunotherapy Found to Increase Progression-Free Survival in Mantle Cell Lymphoma


Combination treatment with ibrutinib found to increase median progression-free survival by 2.3 years compared to the placebo.

Older patients with untreated mantle cell lymphoma (MCL) experienced prolonged survival and clinical benefits when treated with a combination of ibrutinib, bendamustine, and rituximab, and follow up with rituximab maintenance therapy, according to a study published in The New England Journal of Medicine.

At 84.7 months (median follow-up), the median progression-free survival (PFS) among patients taking ibrutinib was 27.7 months longer than those taking the placebo.

“Given the shorter [PFS] with current standard-care chemoimmunotherapy options, a prolongation of [PFS] in response to primary therapy may provide patients with an improved opportunity for durable disease control in order to prevent or delay relapse,” the study authors wrote.

MCL is considered an uncurable subtype of B-cell non-Hodgkin’s lymphoma. Patients are recommended less aggressive first-line therapy, including bendamustine and rituximab, clinically found to improve PFS and overall survival (OS). Patients could also be prescribed R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), or VR-CAP (bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone) treatments.

The primary end point was PFS from randomization until disease progression or death. Researchers identified secondary end points as different measurements of survival and safety for ibrutinib as a combination therapy. Researchers aimed to determine whether ibrutinib, an oral Bruton’s tyrosine kinase (BTK) inhibitor, could be added to the current first-line treatment and therapy for MCL to increase PFS.

Ibrutinib was studied as a combination therapy on 523 patients with MCL aged 65 years and older in the SHINE trial. Among participants, 261 were randomly assigned a once-daily oral treatment of 560 mg of ibrutinib—they took it until there was disease progression or unacceptable adverse effects. The other 262 patients received the placebo. Patients in both the ibrutinib and placebo groups concurrently took 90 mg of bendamustine for 6 cycles and 375 mg per square meter of rituximab.

When ibrutinib was added to the bendamustine and rituximab treatment and rituximab maintenance therapy, PFS increased to 6.7 years compared to the placebo group.

“This result was longer than published data with the commonly used regimens of R-CHOP, VR-CAP, or bendamustine plus rituximab alone, for which the median progression free survival was 1.5 to 3.5 years,” the study authors wrote.

In the ibrutinib study group, complete response (CR) was 65.5%, which was not statistically significant because the placebo had 57.6% CR. OS was similar between the ibrutinib and control groups.

Among older patients with MCL, disease progression or adverse events (AEs) resulted in the death of nearly 4% more patients in the placebo cohort compared to the ibrutinib cohort. However, ibrutinib contributed to more deaths because of AEs, whereas those in the placebo were more likely to die from the disease itself, according to the study.

Grades 3 and 4 AEs affected 81.5% of patients in the ibrutinib cohort and 77.3% of those in the placebo cohort. Among more than 10% of patients, the most common AEs include neutropenia, pneumonia, lymphopenia, anemia, thrombocytopenia, rash, and leukopenia. The safety of the combination therapy is consistent with previous findings.

“Ibrutinib treatment in combination with standard chemoimmunotherapy significantly prolonged [PFS],” the study authors wrote.


Wang, Michael, Jurczak, Wojciech, Jerkeman, Mats, et al. Ibrutinib plus Bendamustine and Rituximab in Untreated Mantle-Cell Lymphoma. The New England Journal of Medicine. Accessed September 26, 2022.

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