Ten‐year follow‐up after intense chemoimmunotherapy with Rituximab‐HyperCVAD alternating with Rituximab‐high dose methotrexate/cytarabine (R‐MA) and without stem cell transplantation in patients with untreated aggressive mantle cell lymphoma

Abstract

SummaryMantle cell lymphoma (MCL) has a poor overall survival after treatment with conventional chemotherapy. Intense chemoimmunotherapy without consolidation stem cell transplantation is a potential therapeutic option. We report on a prospective Phase II study with rituximab in combination with fractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone (R‐Hyper‐CVAD) alternating with rituximab in combination with high‐dose methotrexate‐cytarabine (R‐MA) in untreated patients with diffuse and nodular MCL and their blastoid variants. Ninety‐seven patients were treated, of whom 97% responded and 87% achieved a complete remission. At 10 years of follow up (median 8 years), the median overall survival (OS) for all patients had not been reached and the median time to failure (TTF) for all patients was 4.6 years, without a plateau in the curves. For the group of patients aged 65 years or younger, the median OS had not been reached and the median TTF was 5.9 years. Multivariate analysis revealed pre‐treatment serum levels of β2 microglobulin, International Prognostic Index (IPI) score and mantle cell IPI (MIPI) score, as predictive of both OS and TTF. We conclude that intense chemoimmunotherapy without stem cell transplantation is effective for untreated aggressive MCL.

The current therapeutic scenario for relapsed mantle cell lymphoma

“…Similar efficiency has been shown for an even more intensified regime [10]; however, only the minority of patients was able to complete the full course in a multicenter setting [11].…”

Mantle Cell Lymphoma: Decision Making for Transplant

“…Although tolerating patients treated with the hyper-CVAD regimen had excellent response and survival rates of greater than 90% at 3 years and 4.6 years of time to treatment failure (TTF at 8yr , 16% if age>65, 46% if age<65) following 10 year observation period 7,38,57,58 , patients treated with conventional therapies have also reported to have similar 3 year survival rates 59,60 . The hyper-CVAD regimen without stem cell transplantation was not associated with a plateau in the survival curves (Figure 4) 57 . In this study, beta-2-microglobulin levels and IPI/MIPI scores were found to predict survival 57 .…”

“…The hyper-CVAD regimen without stem cell transplantation was not associated with a plateau in the survival curves (Figure 4) 57 . In this study, beta-2-microglobulin levels and IPI/MIPI scores were found to predict survival 57 . Hyper-CVAD regimen data may suggest high efficacy of the high-dose Ara-C (HIDAC) regimen, which needs to be tested in further clinical trials.…”

Potential prolongation of PFS in mantle cell lymphoma after R-HyperCVAD: auto-SCT consolidation or rituximab maintenance

“…However, a plateau had not been observed and the median OS had not been reached at the time of publication. 11 Outcomes for patients 465 were compromised by treatment-related toxicities. The Nordic study group treated patients with a dose-intensified CHOP-like regimen (maxi-CHOP) alternating with R-high-dose cytarabine and followed by consolidation high-dose chemotherapy and auto-SCT.…”