Treating patients with mantle cell lymphoma (MCL) with a front-line regimen of ibrutinib and rituximab (IR) produced better progression-free survival (PFS) than the pooled outcomes of rituximab and non-cytarabine-based chemotherapy regimens. These results were presented at the 66th American Society of Hematology Annual Meeting and Exposition.
The findings indicate that IR could be considered a standard of care for the first-line treatment of patients over age 60 with untreated stage II to IV MCL, who were the focus of the ENRICH trial, the researchers say.
“This is the first-ever lymphoma study in the first line to show that a non-chemotherapy approach is better than chemotherapy,” presenting author David Lewis, MD, consultant hematologist at University Hospitals Plymouth NHS Trust in the U.K., told ASH Clinical News. “You could give an oral tablet that works just as well as chemotherapy does.”
In the ENRICH trial, physicians made a pre-randomization choice for a chemotherapy regimen — bendamustine and rituximab (BR) or rituximab, doxorubicin, vincristine, and prednisolone (R-CHOP). Then, patients were randomized to either IR or R-chemo, creating two parallel groupings of IR/BR and IR/R-CHOP.
Researchers randomized 199 patients to receive IR and 198 to receive chemotherapy — with 145 receiving BR and 53 receiving R-CHOP.
The patients’ median age was 74, 74.6% were male, 94.5% had an ECOG score of 0 to 1, 56.5% had a high-risk MIPI score, and 6.4% had blastoid MCL.
The overall median PFS for the IR group was 65.3 months compared with 42.4 months for the R-chemo group, with a hazard ratio (HR) of 0.69 (95% CI 0.52-0.90; p=0.003).
IR outperformed R-CHOP with regard to PFS and fared comparably to those receiving the BR regimen, researchers found. The median PFS was not reached for the IR group compared with R-CHOP, with a median PFS of 26.6 months for the R-CHOP group (HR=0.37; 95% CI 0.22-0.62). In the IR/BR parallel grouping, median PFS was 65.3 months for IR and 50.5 months for BR (HR=0.91; 95% CI 0.66-1.25).
Five-year overall survival was 57.7% for the IR group compared with 54.5% for R-chemo (HR=0.87; 95% CI 0.64-1.18).
The findings also suggest that those deriving the most benefit from IR seem to be those with less proliferative disease, Dr. Lewis said.
Over the treatment and maintenance phases, 61.1%, 51.9%, and 51.7% had grade 3 non-hematologic adverse events (AEs) in the IR, R-CHOP, and BR groups, respectively. Grade 3 or greater hematologic AEs were reported in 16.7%, 50.0%, and 33.6% in those groups, respectively. Grade 3 or greater atrial fibrillation was reported in 6.6% of the IR group and 0.5% of the R-chemo group. Quality-of-life scores were higher at mid-treatment for the IR arm compared with R-chemo, researchers reported.
Dr. Lewis said one of the main messages from the trial will likely stem from the poor showing for the R-CHOP regimen.
“It's likely to reduce use of R-CHOP as a first-line treatment,” he said, “because I think the outcomes for the R-CHOP patients were much worse than we expected.”
Any conflicts of interest declared by the authors can be found in the original abstract.
Reference
Lewis DJ, Jerkeman M, Sorrell L, et al. Ibrutinib-rituximab is superior to rituximab-chemotherapy in previously untreated older mantle cell lymphoma patients: results from the international randomised controlled trial, Enrich. Abstract 235. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; December 7, 2024; San Diego, California.
