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Long-Term Follow-up of High-Dose Cytarabine and Autologous Stem Cell Transplantation in Mantle Cell Lymphoma


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Long-term results of the phase III Mantle Cell Lymphoma Younger Trial were reported in the Journal of Clinical Oncology by Hermine et al. They showed a maintained advantage in time to treatment failure and an overall survival advantage with R-CHOP/R-DHAP (alternating rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone/rituximab plus dexamethasone, high-dose cytarabine, and cisplatin) followed by high-dose cytarabine-containing myeloablative chemoradiation and autologous stem cell transplantation (R-DHAP group) vs R-CHOP followed by standard myeloablative chemoradiation and autologous stem cell transplantation (R-CHOP group) in patients younger than age 66 with advanced mantle cell lymphoma.

Study Details

In the open-label European Mantle Cell Lymphoma Network trial, 466 evaluable patients were randomly assigned between July 2004 and March 2010 to the R-DHAP group (n = 232) or R-CHOP group (n = 234). A prior report with a median follow-up of 6.1 years showed a significant benefit in time to treatment failure (primary endpoint) in the R-DHAP group (hazard ratio [HR] = 0.56, P = .038); no significant overall survival difference was observed.

Key Findings

After a median follow-up of 10.6 years, median time to treatment failure remained significantly improved in the R-DHAP group vs the R-CHOP group (8.4 vs 3.9 years, HR = 0.59, P = .038). Rates of freedom from treatment failure at 5 and 10 years were 64% vs 41% and 46% vs 25%, respectively.

Median overall survival was not reached in the R-DHAP group vs 11.3 years in the R-CHOP group (unadjusted HR = 0.80, 95% confidence interval [CI] = 0.61–1.06, P = .12). Rates at 5 and 10 years were 76% vs 69% and 60% vs 55%, respectively. In analyses adjusting for Mantle Cell Lymphoma International Prognostic Index (MIPI; HR = 0.74, 95% CI = 0.56–0.98, P = .038) and MIPI plus Ki-67 (HR = 0.60, 95% CI = 0.41–0.87, P = .0066), the overall survival benefit in the R-DHAP group was statistically significant.

The R-DHAP group had a numerically higher 10-year cumulative incidence of secondary hematologic malignancies (4.5% vs 1.4%, P = .14). The 10-year cumulative incidence of secondary solid tumors was 7.4% vs 9.0% (P = .42).

The investigators concluded, “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 overall survival. Some patients with mantle cell lymphoma may be cured.”

Olivier Hermine, MD, PhD, of the Department of Hematology, Necker Hospital, University Paris Descartes, Paris, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the European Commission, Lymphoma Research Foundation, and Roche. For full disclosures of the study authors, visit ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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