Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study

Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. Although 5-year survival rates in the first-line setting range from 60% to 70%, up to 50% of patients become refractory to or relapse after treatment. Published analyses of large-scale outcome data from patients with refractory DLBCL are limited. SCHOLAR-1, an international, multicohort retrospective non-Hodgkin lymphoma research study, retrospectively evaluated outcomes in patients with refractory DLBCL which, for this study, was defined as progressive disease or stable disease as best response at any point during chemotherapy (>4 cycles of first-line or 2 cycles of later-line therapy) or relapsed at ≤12 months from autologous stem cell transplantation. SCHOLAR-1 pooled data from 2 phase 3 clinical trials (Lymphoma Academic Research Organization-CORAL and Canadian Cancer Trials Group LY.12) and 2 observational cohorts (MD Anderson Cancer Center and University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence). Response rates and overall survival were estimated from the time of initiation of salvage therapy for refractory disease. Among 861 patients, 636 were included on the basis of refractory disease inclusion criteria. For patients with refractory DLBCL, the objective response rate was 26% (complete response rate, 7%) to the next line of therapy, and the median overall survival was 6.3 months. Twenty percent of patients were alive at 2 years. Outcomes were consistently poor across patient subgroups and study cohorts. SCHOLAR-1 is the largest patient-level pooled retrospective analysis to characterize response rates and survival for a population of patients with refractory DLBCL.

Figure 1.

Patient inclusion and search criteria in SCHOLAR-1. Diagram of (A) patients with refractory DLBCL included in the SCHOLAR-1 analysis and (B) search criteria for refractory DLBCL included in SCHOLAR-1. CCTG, Canadian Cancer Trials Group; PD, progressive disease; R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone; SD, stable disease.

Figure 2.

Response rates by subgroup. The vertical line within the plot represents the objective response rate of 26%. CI, confidence interval; N, the total number of patients in the patient subgroup; n, the number of patients with response.

Figure 3.

Overall survival from commencement of salvage therapy. Shown for the (A) overall population, (B) refractory subgroups, (C) tumor response, and (D) post-refractory transplantation status (Kaplan-Meier).