Long-term follow up of the Mantle Cell Lymphoma (MCL) Younger trial has confirmed the primary results of the study, demonstrating prolonged time to treatment failure, and showed a significant improvement in overall survival (OS) adjusted for prognostic factors in patients with advanced-stage MCL treated with an induction regimen of alternating rituximab plus dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP) and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) relative to those treated with R-CHOP induction prior to stem-cell transplantation.1 The updated findings were published in the Journal of Clinical Oncology.
The randomized, open-label, phase 3 trial was initiated by the European MCL Network in 2004 to evaluate first-line treatment of patients with advanced-stage MCL who were younger than 66 years of age (ClinicalTrials.gov Identifier: NCT00209222).
At a median follow-up duration of 6.1 years, the primary results demonstrated superiority in time to treatment failure (hazard ratio [HR], 0.56; P =.038).2 However, this was not the case for OS for an alternating 3´ R-CHOP/R-DHAP induction regimen followed by high-dose cytarabine-containing myeloablative radiochemotherapy conditioning and autologous peripheral blood stem-cell transplantation (R-CHOP/R-DHAP arm) over a 6´ R-CHOP induction regimen followed by standard myeloablative radiochemotherapy and autologous stem-cell transplantation (R-CHOP arm).
A total of 466 patients who were randomly assigned to either the R-CHOP (n=234) or R-CHOP/R-DHAP (n=232) arms were included in the long-term analysis.1 After a median follow-up duration of 10.6 years, the investigators found the time to treatment failure was still significantly longer in the R-CHOP/R-DHAP arm compared with the R-CHOP arm (median, 8.4 vs 3.9 years; 5-year rate, 64% vs 41%; 10-year rate, 46% vs 25%; HR, 0.59; P =.038).
The team found the median OS was longer (not reached) in the R-CHOP/R-DHAP arm than the R-CHOP arm, but the difference was not significant in the unadjusted analysis (not reached vs 11.3 years; 5-year rate, 76% vs 69%; 10-year rate, 60% vs 55%; HR, 0.80; P =.12). When adjusting for MCL International Prognostic Index (MIPI) and MIPI + Ki-67 (MIPI-c), they found the OS adjusted hazard ratios (aHR) reached significance (MIPI aHR, 0.74; P =.038; MIPI-c aHR=.60; P =.0066).
“With mature long-term data, we confirm the previously observed substantially prolonged time to treatment failure and, for the first time to our knowledge, show an improvement of OS. Some patients with MCL may be cured,” the investigators concluded in their report.
Disclosure: This research was supported by Roche. Please see the original reference for a full list of disclosures.
- Hermine O, Jiang L, Walewski J, et al. High-Dose cytarabine and autologous stem-cell transplantation in mantle cell lymphoma: long-term follow-up of the randomized mantle cell lymphoma younger trial of the European mantle cell lymphoma network. J Clin Oncol. 2023;41(3):479-484. doi:10.1200/JCO.22.01780
- Hermine O, Hoster E, Walewski J, et al. Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL Younger): a randomised, open-label, phase 3 trial of the European Mantle Cell Lymphoma Network. Lancet. 2016;388(10044):565-575. doi:10.1016/S0140-6736(16)00739-X