High-dose Ara-C (also known as cytarabine) should be used in the induction regimen for younger patients with mantle-cell lymphoma (MCL) who are undergoing autologous stem-cell transplantation (ASCT), the final results of the MCL Younger Trial of the European MCL network showed.
In this trial, the use of 3 alternating courses of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and rituximab plus dexamethasone, cytarabine, and cisplatin (R-DHAP) increased the clinical complete response (CR) rate and molecular responses compared with R-CHOP alone in patients with MCL after induction.
The combined regimen also im-proved time to treatment failure in all risk groups and was associated with increasing numbers of patients who were negative for minimal residual disease—which is a factor for good prognosis, said Olivier Hermine, MD, PhD, Head, Department of Hematology at Hôpital Necker, and Professor of Hematology at the University of Paris Descartes, France.
In addition, this regimen showed a trend toward improved overall survival, with a good safety profile.
“Regimens that include high-dose Ara-C should become the new gold standard,” Dr Hermine maintained.
The study compared 3 alternating courses of R-CHOP and R-DHAP followed by a high-dose Ara-C–containing myeloablative regimen and ASCT versus 6 courses of R-CHOP followed by myeloablative radiochemotherapy and ASCT in 497 younger patients (aged <65 years) with stage II to IV MCL.
After induction, the response rates were significantly higher in the Ara-C–containing arm, with CRs achieved by 25% in the R-CHOP arm versus 36% in the R-CHOP plus R-DHAP arm (P = .077); the rates of CR or unconfirmed CR (CRu) were 39% versus 55%, respectively (P = .013).
The rates of CR, CRu, or partial response (PR) were similar in both arms (90% and 95%, respectively).
ASCT was possible for approximately 80% per arm, and posttransplant response rates were high in both arms (approximately 98%).
After a median follow-up of 53 months, the median time to treatment failure was 46 months in the R-CHOP arm versus 88 months in the R-CHOP plus R-DHAP arm (P = .038), and R-CHOP–treated patients had almost twice the number of events related to treatment failure: 122 versus 69 with R-CHOP plus R-DHAP.
In addition, the relapse rate after CR/Cru/PR was twice as high in the R-CHOP arm (88 vs 44, respectively).
The significant differences in time to treatment failure favoring the R-CHOP plus R-DHAP arm were present in the low-risk and in the intermediate-risk groups.
The achievement of minimal residual disease after induction was the strongest independent prognostic factor of outcome, and other studies have suggested that this is significantly associated with prolonged remission.
Compared with R-CHOP, inductions with R-CHOP plus R-DHAP were associated with higher rates of grade 3 or 4 myelosuppression and similar rates of other grades 3 and 4 toxicities. Transplant-related toxicities were similar between the arms.
Median survival has not been reached in either arm, although the preliminary findings suggest that survival will be best for the low-risk group of younger patients with MCL, with a strong trend favoring treatment with R-CHOP plus R-DHAP.