Acalabrutinib and Bendamustine-Rituximab Improve MRD Negativity in MCL

In a significant advancement for the treatment of mantle cell lymphoma (MCL), a recent analysis from the phase 3 ECHO trial presented at the 2025 European Hematology Association (EHA) Congress has demonstrated that the combination of acalabrutinib and bendamustine-rituximab (BR) significantly prolongs the duration of minimal residual disease (MRD) negativity compared to BR alone. This finding underscores the potential of MRD negativity as a crucial prognostic biomarker for patient outcomes in MCL.

The study involved 299 previously untreated MCL patients, with a data cutoff on February 15, 2024. Among these, 266 patients in the acalabrutinib arm were evaluated for MRD negativity using the ClonoSEQ assay, which measures MRD at a threshold of 10^(-5). The results indicated that 70.7% of patients receiving acalabrutinib achieved MRD negativity at week 24, compared to 67.9% in the placebo group. Notably, the median time to reach MRD negativity was consistent across both groups at 24 weeks.

Dr. Michael Wang, a leading researcher and professor at The University of Texas MD Anderson Cancer Center, emphasized the relevance of MRD as a predictor of progression-free survival (PFS) and overall survival (OS). According to Wang, patients who achieved MRD negativity exhibited significantly longer median PFS—67.81 months for those with clinical complete response (CR) versus 21.91 months for those who remained MRD positive. "In our analysis, MRD was a stronger prognostic factor for outcome compared to clinical response," stated Wang during the presentation.

The ECHO trial aimed to evaluate the association between MRD status and various baseline high-risk disease features, including TP53 mutation status, a known marker of poor prognosis in MCL. The findings revealed that patients with TP53 mutations had a lower likelihood of achieving and maintaining MRD negativity, illustrating the importance of genetic profiling in personalizing treatment.

The study's design included random assignment of patients to receive either acalabrutinib (100 mg twice daily) combined with BR or placebo with BR across six cycles. Those who responded to induction therapy transitioned to maintenance therapy with rituximab every two months, highlighting the comprehensive treatment strategy employed.

The implications of these findings are profound, not only for clinical practice but also for future research into targeted therapies for MCL. By establishing MRD negativity as a key prognostic indicator, the ECHO trial results contribute to a growing body of evidence advocating for the incorporation of MRD assessments into routine clinical evaluations.

In conclusion, the advancement of acalabrutinib combined with BR represents a promising therapeutic strategy for MCL patients, with MRD negativity serving as a pivotal marker for treatment success and long-term outcomes. Continued research and clinical trials will be essential to further delineate the role of MRD in guiding therapy decisions and improving patient prognoses in the ever-evolving landscape of oncology.