Study Finds Addition of High-Dose Cytarabine to Immunochemotherapy Before Transplant Improves Outcomes in Younger Patients With MCL


Key Points

  • In patients with MCL aged ≤ 65 years, the addition of high-dose cytarabine to immunochemotherapy before ASCT significantly prolonged time to treatment failure.
  • Severe hematologic adverse events were more common in the cytarabine group.

The phase III European MCL Younger trial has shown that adding high-dose cytarabine to immunochemotherapy prior to autologous stem cell transplantation (ASCT) increased the time to treatment failure among patients with mantle cell lymphoma (MCL) aged ≤ 65 years. The results were reported by Hermine et al in The Lancet.

Study Details

In this open-label trial, 497 patients with previously untreated stage II to IV disease from 128 sites in Germany, France, Belgium, and Poland were randomized between July 2004 and March 2010 to receive six courses of alternating R-CHOP (rituximab [Rituxan] plus cyclophosphamide, doxorubicin, vincristine, and prednisone) or R-DHAP (rituximab plus dexamethasone, high-dose cytarabine, and cisplatin) followed by a high-dose cytarabine-containing conditioning regimen and ASCT (cytarabine group; n = 248) or six courses of R-CHOP followed by myeloablative radiochemotherapy and ASCT (control group; n = 249).

Patients had a median age of 55 years. The primary outcome was time to treatment failure from randomization to stable disease after at least four induction cycles, disease progression, or death from any cause. The primary analysis was among 232 cytarabine patients and 234 control patients in whom treatment was started according to randomization (modified intent-to-treat population).

Key Outcomes

Median follow-up was 6.1 years. In the primary analysis, median time to treatment failure was 9.1 years (95% confidence interval [CI] = 6.3 years to not reached) in the cytarabine group vs 3.9 years (95% CI = 3.2–4.4 years) in the control group (hazard ratio [HR] = 0.56, P = .038). Five-year freedom from treatment failure was 65% (95% CI = 57%–71%) vs 40% (95% CI = 33%–46%). In the full intent-to-treat population, median time to treatment failure was 9.1 vs 4.0 years (HR = 0.53, P < .0001).

Median progression-free survival from randomization was 9.1 vs 4.3 years (HR = 0.55, P < .0001), and 5-year rates were 65% vs 44%. At the time of analysis, there was no significant difference in overall survival (median = not reached vs 9.8 years, HR = 0.78, P = .12), with 5-year rates of 76% vs 69%, respectively.


During induction immunochemotherapy, patients in the cytarabine group had a higher frequency of grade 3 or 4 hematologic toxicity, including anemia (29% vs 8%) and thrombocytopenia (73% vs 9%), grade 3 or 4 febrile neutropenia (17% vs 8%), and grade 1 or 2 renal toxicity (43% vs 10%). ASCT-related death occurred in eight patients (3.4%) in each group.

The investigators concluded: “Immunochemotherapy containing high-dose cytarabine followed by ASCT should be considered standard of care in patients aged 65 years or younger with mantle cell lymphoma.”

The study was funded by the European Commission, the Lymphoma Research Foundation, and Roche.

Martin Dreyling, MD, of Ludwig-Maximilians-University Hospital, is the corresponding author of The Lancet article.

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