Study Finds No Added Benefit of Auto-HCT for MCL Patients in Deep Remission
Consolidative autologous hematopoietic cell transplant (auto-HCT) provides no additional benefit for patients with mantle cell lymphoma (MCL) who achieve undetectable minimal residual disease (uMRD6) in their first complete remission (CR), according to an interim analysis from the EA4151 trial presented at the 66th American Society of Hematology Annual Meeting.
“E4151 explored whether auto-HCT benefits pts achieving deep first remission, as measured by a highly sensitive immunoglobulin high throughput sequencing minimal residual disease (MRD) assay,” explained Timothy Fenske, MD, Medical College of Wisconsin in Milwaukee, WI, and coauthors.
The US National Clinical Trials Network and Blood and Marrow Transplant Clinical Trials Network conducted the trial, in which 650 patients with MCL aged 18 to70 were enrolled. Participants in the first CR were assessed with positron emission tomography/computed tomography (PET/CT), bone marrow biopsy, and the clonoSEQ® MRD assay. Those with uMRD6 were randomized to receive either auto-HCT with 3 years of rituximab maintenance (Arm A) or rituximab maintenance alone (Arm B). Patients with MRD-positive (MRD+) or MRD-indeterminate CR (Arms C and D, respectively) received auto-HCT plus rituximab maintenance.
At a median follow-up of 2.7 years, overall survival (OS) and progression-free survival (PFS) rates were similar between Arms A and B. Three-year OS for all randomized patients was 82.1% in Arm A and 82.7% in Arm B, while PFS was 76.6% and 77.4%, respectively. Exploratory analyses revealed that MRD+ patients who converted to uMRD6 after auto-HCT (n=17) had a strikingly favorable prognosis, with 100% OS and PFS at 3 years, compared with 63.6% OS and 48.8% PFS for those who remained MRD+ (n=13). Most patients (73%) underwent intensive induction regimens, with high-dose cytarabine commonly employed, and a small subset (7.2%) received Bruton tyrosine kinase (BTK( inhibitors during induction.
“In this interim analysis, in the era of highly effective induction and maintenance regimens, MCL pts in first CR with uMRD6 did not benefit from consolidative auto-HCT. Pts who remain MRD+ after induction may benefit from auto-HCT,” concluded the study authors.
Reference
Fenske TS, Wang XV, Till BG, et al. Lack of benefit of autologous hematopoietic cell transplantation (auto-HCT) in mantle cell lymphoma (MCL) patients (pts) in first complete remission (CR) with undetectable minimal residual disease (uMRD): Initial report from the ECOG-ACRIN EA4151 phase 3 randomized trial. Blood. 2024;144(Suppl 2):LBA-6. doi:10.1182/blood-2024-212973.
