VcR-CVAD Induction Chemotherapy Followed by Maintenance Rituximab Produces Durable Remissions in Mantle Cell Lymphoma: A Wisconsin Oncology Network Study

Abstract

Introduction VcR-CVAD was developed as an intermediate-intensity induction regimen with maintenance rituximab (MR) to improve remission durations after first-line therapy for mantle cell lymphoma (MCL) in older and younger MCL patients. Patients and Methods Patients with previously untreated MCL received VcR-CVAD induction chemotherapy for 6 cycles (21-day cycles). Patients achieving at least a partial response received rituximab consolidation (375 mg/m2 × 4 weekly doses) and MR (375 mg/m2 every 12 weeks × 20 doses). The primary end points were overall and complete response (CR), and secondary endpoints were PFS and overall survival (OS). Thirty patients were enrolled, with a median age of 61 years. There was an even distribution of patients <60 years and ≥60 years. MIPI medium- or high-risk disease was present in 60%. Overall response rate observed was 90% (77% CR/unconfirmed CR). After a median follow-up of 7.8 years, the 6-year PFS and OS were 53% and 70%, respectively. There was no difference in 6-year PFS or OS between the younger (age <60) and older (age ≥60) subgroups. In a univariate analysis, LDH when analyzed for interaction with age had a significant effect on PFS outcomes at 6 years. There were no pre-treatment variables determined to have a significant effect on OS outcomes at 6 years. Conclusions Long-term outcomes with VcR-CVAD are comparable with more intensive inductions and consolidation approaches. MCL is biologically heterogeneous and durable remission can be achieved with intermediate intensity therapy. Maintenance rituximab appears to contribute to these excellent outcomes.

Current overview and treatment of mantle cell lymphoma

“…Treatment broadly consists of two components: cytarabine-containing induction chemotherapy followed by ASCT. Phase II trials in the past decade have consistently demonstrated the impressive activity of cytarabine in MCL, namely in the Hyper-CVAD and VcR-CVAD regimens 11 – 13 . Since that time, the MCL Younger trial conducted by the European MCL Network provided phase III data to support cytarabine as the key agent in MCL induction 14 .…”

Current trials for frontline therapy of mantle cell lymphoma

“…This regimen showed improved results with an ORR of 90% and a CRR of 77%. The 6-year PFS and OS were 53 and 70% respectively, and there was no difference of 6-year PFS and OS between the age subgroups (age < 60 years and age ≥ 60 years) [ 27 ].…”

Phase 1–2 study of vorinostat (SAHA), cladribine and rituximab (SCR) in relapsed B‐cell non‐Hodgkin lymphoma and previously untreated mantle cell lymphoma

“…However, the response rates and PFS seen with the SCR regimen compare favourably with other less intensive induction regimens. For example, the CR rate with SCR was higher than that seen in prospective studies using BR (40%), R‐cladribine (52%), R‐CHOP (34–42%), and VR‐CAP (rituximab, cyclophosphamide, doxorubicin and prednisone plus bortezomib; 53%) (Kluin‐Nelemans et al , ; Robak et al , ; Chen et al , ; Le Gouill et al , ; Visco et al , ; Chang et al , ; Ruan et al , ; Tam et al , ). Furthermore, although MRD testing was only available for 14 responding patients, all were MRD‐negative after induction.…”

“…Improvement in outcomes is particularly notable for mantle cell lymphoma (MCL); however, relapse and death remain the norm (Schmidt & Dreyling, ; Herrmann et al , ; Chandran et al , ) and much of the progress seen to date has been demonstrated in younger patients (age <60–65 years) who are eligible for aggressive treatment (LaCasce et al , ). Despite recent advances, it remains unknown if less intense therapy is inferior to aggressive treatment and poor risk patients continue to have poor outcomes (Kluin‐Nelemans et al , ; Robak et al , ; Le Gouill et al , ; Visco et al , ; Chang et al , ; Obr et al , ; Ruan et al , ; Tam et al , ). Identifying treatment strategies that incorporate novel therapeutic approaches irrespective of patient age remains a high priority.…”