Optimizing First-Line Therapy to Improve Survival for Patients With Relapsed MCL

Mantle cell lymphoma (MCL) remains an incurable disease despite advances in treatment that have extended overall survival (OS), according to researchers who presented during the 2024 American Society of Hematology Annual Meeting. They noted that relapses are inevitable, necessitating multiple treatment lines. Their research provided real-world, prospective data on patients with relapsed MCL, characterizing outcomes across successive therapies and highlighting challenges in disease management.

The study included 588 patients from 73 sites in the UK, enrolled between 2014 and 2019. The median follow-up was 5.7 years. Patients had a median age of 70 years, with 84% presenting with advanced disease (stage III or IV). First-line (1L) treatment was administered to 86% of patients at a median time to treatment of 1.4 months; only 29% progressed to second-line (2L) treatment, with further attrition across subsequent lines. Notably, only six patients (1%) underwent allogeneic stem cell transplantation.

The median OS and event-free survival (EFS) after 1L treatment were 69.5 and 46 months, respectively. However, patients with progression of disease within 24 months (POD24) had significantly worse outcomes, with a median OS of 25.3 months compared with 70.1 months for those without POD24. After 2L treatment, OS and EFS decreased to 20.3 and 15 months, respectively. Survival metrics further declined with each additional treatment line, emphasizing the diminishing efficacy of subsequent therapies.

Treatment choice significantly influenced outcomes. Among 1L regimens, Bruton tyrosine kinase inhibitor (BTKi)–containing therapies demonstrated a median OS of 69.1 months;  bendamustine and R-CHOP regimens yielded shorter OS. Patients receiving the Nordic (Maxi-CHOP) regimen or high-dose cytarabine regimens experienced the most favorable outcomes, with many undergoing autologous stem cell transplantation. In 2L treatment, BTKi-based regimens were predominant, but efficacy diminished when they followed a round of  1L BTKi therapy.

“This prospective analysis confirms a progressive reduction in survival and response with successive treatment lines for relapsed MCL,” the authors noted.

“This patient-level longitudinal follow up highlights the need to optimize 1L treatment. Advancing age impacts OS and TTNT/death following 1L treatment. Time to POD from 1L treatment was associated with OS. RBAC [rituximab, bendamustine, cytarabine] was the most common 2L treatment following 1L BTKi.”

Reference

Mant S, Naylor G, Crosbie N, et al. A prospective analysis of outcomes following successive lines of treatment in mantle cell lymphoma in an unselected previously untreated population: The UK MCL Biobank. Abstract #1641. Presented at the American Society of Hematology Annual Meeting; December 7-10, 2024; San Diego, California.