High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) may not improve survival for patients with mantle cell lymphoma (MCL) who achieve remission after initial treatment. These findings were presented by Fenske et al. at the 2024 American Society of Hematology (ASH) Annual Meeting & Exposition.
Study Background
MCL is an incurable hematologic malignancy predominantly affecting older male patients. While historically associated with poor outcomes, recent advancements in targeted therapies and immunotherapies have improved remission rates. For patients under 70, ASCT has been a common practice, involving high-dose chemotherapy followed by reinfusion of the patient’s own blood stem cells.
According to Dr. Timothy S. Fenske, Professor of Medicine at the Medical College of Wisconsin, the EA4151 trial is the first randomized study to assess ASCT in MCL patients with undetectable MRD in first remission, within an era of highly effective induction and maintenance regimens.
Trial Design and Key Findings
The phase III EA4151 study enrolled 650 patients between August 2017 and July 2024. Patients underwent PET/CT imaging, bone marrow biopsies, and blood draws to assess MRD using a highly sensitive assay. Patients in first complete remission after induction therapy were eligible and were then randomized. The trial was conducted across cancer centers and community hospitals via the National Clinical Trials Network and the Blood and Marrow Transplant Clinical Trials Network.
The primary hypothesis was that patients in deep remission with negative PET/CT scans, bone marrow biopsies, and MRD testing might not benefit from ASCT, potentially avoiding unnecessary risks.
The study found that 79% (n = 516) of patients achieved complete remission with undetectable MRD after induction therapy. These patients were randomized to either ASCT followed by 3 years of rituximab (arm A, n = 257) or 3 years of rituximab alone (arm B, n = 259). The primary endpoint was overall survival.
After a median follow-up of 2.7 years, the 3-year overall survival rates were 82.1% in the ASCT plus rituximab group and 82.7% in the rituximab alone group. The remaining patients, who experienced either MRD-positive complete remission or partial response (arm C, n = 49) or MRD-indeterminate or partial response with undetectable MRD (arm D, n = 85), received ASCT plus 3 years of rituximab. The 3-year overall survival was 81.9% in arm C and 85.1% in arm D.
Progression-free survival, a secondary endpoint, showed similar 3-year rates across all groups: 76.6%, 77.4%, 76.9%, and 73.4% in arms A through D, respectively.
The ECOG-ACRIN Data Safety and Monitoring Committee halted enrollment early after an interim analysis revealed no statistically significant differences in overall survival between the groups. A futility analysis indicated similar outcomes would likely persist with full enrollment.
Implications and Future Directions
According to Dr. Fenske, patients with MCL in first complete remission with undetectable MRD did not benefit from consolidative ASCT in this interim analysis. He noted that patients remaining MRD-positive after induction might still benefit from ASCT, and longer follow-up is needed to confirm these findings.
