Michael Wang, MD, spoke about key data from the phase 3 SHINE trial which analyzed the use of first-line ibrutinib plus bendamustine and rituximab in older patients with mantle cell lymphoma.
Michael Wang, MD, Puddin Clarke Endowed Professor, professor of the Department of Lymphoma & Myeloma and the Department of Stem Cell Transplantation in the Division of Cancer Medicine at MD Anderson Cancer Center in Houston, Texas, spoke with CancerNetwork® regarding results from the phase 3 SHINE trial (NCT01776840). The trial analyzed the efficacy of first-line ibrutinib (Imbruvica) plus bendamustine (Bendeka) and rituximab (Rituxan) compared with placebo in older patients with mantle cell lymphoma.
The median progression-free survival was 80.6 months in the combination arm vs 52.9 months in the placebo arm. In the combination arm, the complete response was 65.5% vs 57.6% in the placebo arm (P = .0567). Additionally, there was no significant difference in overall survival between arms (P = .648).
The SHINE trial is a phase 3 clinical trial [comparing] the combination of ibrutinib plus bendamustine and rituximab vs placebo, with [bendamustine/rituximab] in elderly patients who have newly diagnosed mantle cell lymphoma. There is a greater discrepancy between young and older patients treated in the first-line [setting] when they are diagnosed with mantle cell lymphoma. Because the younger patients can tolerate intensive therapy, their survival is over 10 years. When we are treating older patients, however, they are not able to tolerate intensive chemotherapy, so, we use less intensive therapies; the most commonly used are bendamustine plus rituximab and R-CHOP [rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone]. Unfortunately, those are related to the best progression-free survival of over 3 years to 3.5 years and their overall survival is about 5 years. Younger patients can survive over 10 years and older patients survive only about 5 years. That’s a great discrepancy.
In order to close this discrepancy, we tried to add the very active agent ibrutinib, which is an oral therapy, to the bendamustine plus rituximab arm to see if we can prolong the progression-free survival and then after possibly overall survival. In this clinical trial, we showed in the ibrutinib plus bendamustine and rituximab arm, the primary endpoint of PFS was 6.7 years. However, [the PFS] is significantly less in the placebo arm [at] only 4.4 years. Although the overall survival is not different, it is because the overall survival is not the primary end point of this clinical trial.
Wang M, Jurczak W, Jerkman 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. Published online 2022;40(suppl 17):LBA7502. doi:10.1200/JCO.2022.40.17_suppl.LBA7502