Sustained Benefit of Cytarabine Conditioning in MCL Patients Undergoing Transplant

Five-year follow-up data from the phase III MCL Younger trial found a sustained benefit associated with high-dose cytarabine conditioning prior to autologous stem cell transplantation (ASCT) in patients with mantle cell lymphoma (MCL) who received induction therapy with chemoimmunotherapy. These findings were presented at the 2021 American Society of Hematology Annual Meeting.

Initial Findings from MCL Younger

MCL Younger is a randomized phase III trial of first-line treatment for stage II-IV MCL in patients aged younger than 66 years who are considered eligible for ASCT. Patients were assigned to one of two treatment arms with varying pre-transplant conditioning regimens:

  • the experimental arm involved induction with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) or R-DHAP (dexamethasone, high-dose cytarabine, and cisplatin), followed by high-dose cytarabine consolidation with ASCT
  • the control arm received R-CHOP followed by myeloablative chemoradiotherapy and ASCT

In the initial analysis of MCL Younger, five-year time to treatment failure (TTF) was significantly greater in the cytarabine conditioning arm than the control arm (65% vs. 40%; p = 0.038). At the 2021 ASH Annual Meeting, lead author Olivier Hermine, MD, PhD, from the University of Paris in France, shared long-term follow-up data from a median follow-up of 11 years.

In total, 466 patients were analyzed, and the median age was 55 years (range = 30-67). MCL International Prognostic Index (MIPI) scores were similar between the experimental and control arms (low, 65% and 60%; intermediate, 22% and 26%; high, 13% and 14%).

Five-Year Outcomes after Cytarabine Treatment

At longer-term follow-up, the difference in TTF was still significant in favor of the experimental arm (hazard ratio [HR] = 0.59; p = 0.038), the researchers reported. Median overall survival (OS) was not reached yet in the R-CHOP/R-DHAP arm and was 11.3 years in the R-CHOP–only arm (p = 0.12). Five-year and 10-year probability of OS was 76% and 60% in the experimental arm, respectively, compared with 69% and 55% in the control arm (unadjusted HR = 0.80; p = 0.12). When adjusted for MIPI score, the probability of OS remained significantly higher in the experimental arm (p ≤ 0.038).

The authors also evaluated the cumulative incidence of secondary hematologic malignancies as a secondary endpoint. Although not statistically significant, the cumulative incidence of secondary hematologic malignancies was higher in the R-DHAP arm (9 events vs. 4 events; at 10 years, 4.5% vs. 1.4%, p = 0.14).

“With an additional five years of median follow-up, our results on first-line treatment of MCL patients younger than 66 years confirm the previously observed substantially prolonged TTF by the addition of high-dose [cytarabine],” the authors concluded. “In the future, avoidance of total body irradiation and ASCT, as investigated in the TRIANGLE protocol, may reduce secondary malignancies after R-CHOP/R-DHAP. These data suggest that some patients may be functionally cured by optimal first line treatment and may challenge future chemotherapy-free strategies in MCL.”