Dr Fenske on the Rationale of Assessing Rituximab With or Without ASCT in MRD-Negative MCL

“Patients [with mantle cell lymphoma (MCL)] were treated with whatever induction regimen their physician chose to use. We designed the study that way, acknowledging that there are [several] different [induction] regimens that are in use in the United States for MCL, we just required that they receive a [rituximab (Rituxan)] plus chemotherapy combination.”

Timothy S. Fenske, MD, MS, medical oncologist, professor of medicine, the Froedtert & Medical College of Wisconsin, details the rationale of the phase 3 ECOG-ACRIN EA4151 trial (NCT03267433) investigating the use of consolidative autologous stem cell transplant (ASCT) followed by rituximab or rituximab alone in patients with MCL who achieved a minimal residual disease (MRD)–negative complete remission following frontline induction therapy.

Data from the study were presented at the 2024 ASH Annual Meeting.

The patient population enrolled on the phase 3 study included those with MCL who were undergoing first-line therapy and achieved CR, Fenske begins. The design of the study permitted patients to be treated with a physician’s choice induction regimen to represent different induction regimens used in the United States for MCL, he says. However, he explains that patients were required to be treated with a rituximab plus chemotherapy combination. Acceptable induction regimens included BTK inhibitors, although 7.2% of patients were treated with BTK inhibitors following the completion of induction therapy, he notes.

The primary end point of the study was overall survival (OS) between ASCT plus maintenance rituximab vs maintenance rituximab alone. At a median follow-up of 2.7 years, the futility boundary for OS was crossed for ASCT/rituximab vs rituximab alone in all patients randomly assigned (n = 375; HR, 1.11; 95% CI, 0.71-1.74) and those treated as assigned (n = 375; HR, 1.00; 95% CI, 0.58-1.74; P = .99) Of note, the 3-year OS rate in all randomly assigned patients was 82.1% in the ASCT/rituximab arm vs 82.7% in the rituximab monotherapy arm.

Patients were then assessed with a PET/CT scan, bone marrow biopsy, and a highly sensitive next-generation MRD assay called the clonoSEQ assay, Fenske continues. He explains that the assay is more sensitive, as it can detect 1 in 1 million lymphoma cells. Following these assessments, patients in CR with undetectable MRD were eligible for randomization, Fenske concludes.