Outcome following Reduced-Intensity Allogeneic Stem Cell Transplantation (RIC AlloSCT) for Relapsed and Refractory Mantle Cell Lymphoma (MCL): A Study of the British Society for Blood and Marrow Transplantation

Abstract

Reduced-intensity allogeneic stem cell transplantation (RIC-AlloSCT) is being increasingly considered for patients with aggressive lymphoma, but limited evidence exists in mantle cell lymphoma (MCL). We report a retrospective study of transplant outcomes of RIC-AlloSCT for MCL in 70 patients (median age, 48 years, range: 30-67 years), with 57 patients receiving an Alemtuzumab-containing regimen. Thirty-four percent of patients had received a prior autologous stem cell transplant. The 1- and 5-year nonrelapse mortality (NRM) was 18% (95% confidence interval [CI] 10-27) and 21% (95% CI 12-31), respectively. The incidence of severe (grade III and IV) acute graft-versus-host disease (aGVHD) was 10%, and the 5-year incidence of chronic GVHD (cGVHD) was 61%. The cumulative relapse risk was 65% (95% CI 48-77) at 5 years, significantly affected by disease status at transplant (P = .0495), specifically the presence of chemosensitive disease (P = .0364). Fifteen of 18 relapsed patients received donor lymphocyte infustion (DLI) (n = 14) or a second RIC-AlloSCT (n = 1), with 11 of 15 currently in CR. The 5-year overall survival (OS) and progression-free survival (PFS) were 37% (95% CI 25%-56%) and 14% (95% CI 6%-34%), respectively. Age at transplantation and having <2 prior lines of therapy influenced the OS, whereas having <2 prior lines of therapy was the only factor to influence PFS. The use of Alemtuzumab in the conditioning was associated with an improved OS at 3 years (P = .0271). RIC-AlloSCT is a potential treatment modality for aggressive MCL. For patients relapsing post-AlloSCT, the disease is salvageable with DLI. The timing of RIC-AlloSCT should be explored in prospective studies to establish the optimal role in the management of this aggressive lymphoma.

Detection of minimal residual disease following induction immunochemotherapy predicts progression free survival in mantle cell lymphoma: final results of CALGB 59909

“…23 Second, will MRD positive patients after intensive induction immunochemotherapy benefit from allogeneic stem cell transplant (Allo-SCT) instead of ASCT at first remission? A recent retrospective study clearly demonstrated that age and the effects of prior therapies predict OS and NRM (non-relapse mortality) after RIC (reduced-intensity conditioning) Allo-SCT in patients with relapsed or refractory MCL, 24 raising the potential value of considering Allo-SCT for the early phase of disease management. Third, could MRD status after intensive induction immunochemotherapy be used to stratify patients for maintenance therapy with either rituximab or another targeted agent, and if sequential monitoring of MRD status could be used to determine the duration of maintenance therapy?…”

Transplantation for mantle cell lymphoma: is it the right thing to do?

“…Retrospective single-and multiinstitutional reviews have shown durable PFS of 14% to 46% and OS of 37% to 53%, with evidence of a plateau in the survival curve suggesting cure. [16][17][18] One-year nonrelapse mortality was 18% to 22%. A beneficial effect of donor lymphocyte infusion was documented in some relapsing patients, consistent with a GVL effect.…”

Is hematopoietic cell transplantation still a valid option for mantle cell lymphoma in first remission in the chemoimmunotherapy-era?

“…The 3-year-PFS of 57 chemosensitive patients (including 30 patients in first CR/PR) in the British registry Transplantation and beyond in MCL L Chaudhary et al study ranged from 26-31%. 56 Non-randomized registry data from Center for International Blood and Marrow Transplant Research examining the role of allo-HCT vs auto-HCT in MCL patients in first remission (1st CR or PR) showed no benefit in terms of PFS (55% vs 52%) or OS (62% vs 61%), but a significantly higher non-relapse mortality (25% vs 3%) with upfront allografting 57 (Table 4). These data caution against the routine use of allo-HCT for MCL in first remission.…”