Ofatumumab plus HyperCVAD/HD-MA induction leads to high rates of minimal residual disease negativity in patients with newly diagnosed mantle cell lymphoma: Results of a phase 2 study.

BACKGROUND: Ofatumumab is a humanized type 1 anti-CD20 monoclonal antibody. Preclinical studies show improved complement-mediated cytotoxicity (CMC) compared to rituximab in mantle cell lymphoma (MCL). This study evaluates the safety and efficacy of combining ofatumumab with HyperCVAD/MA (O-HyperCVAD) in newly diagnosed MCL. METHODS: In this single-arm phase 2 study, 37 patients were treated with the combination of O-HyperCVAD for 4 or 6 cycles, followed by high dose chemotherapy and autologous stem cell transplant. Primary objectives were overall response rate (ORR) and complete response (CR) rate at the end of therapy. Secondary objectives included minimal residual disease (MRD) negativity, progression-free survival (PFS), and overall survival (OS). RESULTS: Median age was 60 years; ORR was 86% and 73% achieved a CR by modified Cheson criteria. The MRD negativity rate was 78% after 2 cycles of therapy, increasing to 96% at the end of induction; median PFS and OS were 45.5 months and 56 months, respectively. Achieving a post-induction CR by both imaging and flow cytometry was associated with improved PFS and OS. Early MRD negativity (post-2 cycles) was also associated with an improved PFS but not OS. There were 3 deaths while on therapy, and grades 3 and 4 adverse events (AEs) were observed in 22% and 68% of the patients. CONCLUSION: The addition of ofatumumab to HyperCVAD/HD-MA led to high rates of MRD negativity by flow cytometry in patients with newly diagnosed MCL. Achieving a CR post-induction by both imaging and flow cytometry is associated with improved overall survival.

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

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 patients with MCL. 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 endpoints were overall and complete response (CR), and the secondary endpoints were progression-free survival (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. Mantle cell lymphoma international prognostic index medium- or high-risk disease was present in 60%. The 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 years) and older (age ≥ 60 years) subgroups. In a univariate analysis, lactate dehydrogenase, when analyzed for interaction with age, had a significant effect on PFS outcomes at 6 years. There were no pretreatment 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. MR appears to contribute to these excellent outcomes.

Hematopoietic cell transplantation for mantle cell lymphoma: predictive value of pretransplant positron emission tomography/computed tomography and bone marrow evaluations for outcomes.

BACKGROUND: The prognostic roles of 18F-fludeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging and marrow involvement evaluation on outcomes following autologous and allogeneic hematopoietic cell transplantation (HCT) for mantle cell lymphoma (MCL) are uncertain and require more data. PATIENTS AND METHODS: We categorized 66 patients with MCL who received HCT (38 autologous and 28 allogeneic) on the basis of pre-HCT residual disease (RD) status as assessed by marrow MCL morphology and flow/molecular analysis and PET/CT imaging to RD positive (RD(+)) (either or both measures positive) and RD(-) (both negative). We analyzed the predictive value of these RD detection methods on transplant outcomes. RESULTS: The 2-year relapse rate after autograft was significantly higher in pre-HCT RD(+) patients (46% [95% CI 16-77%]) than in patients who were RD(-) (19% [95% CI 0-42%]; P = .02), leading to worse 5-year disease-free survival (DFS) in RD(+) patients (46% [95% CI 14%-73%] vs. 68% [95% CI 33-87%], P = .04). In multivariate analysis, RD(+) status was associated with a reduction in DFS (hazard ratio, 5.6; P = .02). Most allogeneic HCT recipients had advanced disease and most were RD(+) (12 PET/CT(+); 5 marrow-positive). The 5-year DFS and relapse rates after allogeneic HCT were 34% and 25% for all patients and 40% and 33% for RD(+) recipients, suggesting that active disease at the time of allograft does not preclude long-term remissions in advanced MCL. CONCLUSION: Both autologous and allogeneic HCT lead to promising long-term survival. RD detected prior to autograft was associated with increased relapse and worse 5 year DFS. Allograft recipients had favorable long-term outcomes even in presence of pre-HCT detectable disease.