Outcomes in refractory diffuse large B-cell lymphoma: results from a multicenter real-world study in China

Abstract

Background: Diffuse large B-cell lymphoma (DLBCL) patients refractory to rituximab-based immunochemotherapy have a dismal prognosis. However, the definition of refractory DLBCL remains inconsistent and no large cohort study data is available from Asian countries. To validate the definition and outcomes of refractory DLBCL in China, we conducted a multicenter, retrospective cohort study.

Methods: The REtrospective AnaLysis of Treatment REspoNse of refractory DLBCL (REAL-TREND) study was performed using real-world data from 8 centers in China. DLBCL patients with curative intent were included in the REAL-TREND dataset. Overall survival (OS) was estimated using the Kaplan-Meier method and compared by the log-rank test. Due to heterogeneity in response rates among different centers, the response rates of refractory patients were pooled using random-effect models. Multivariate survival analysis was performed using the Cox regression model.

Results: A total of 2778 DLBCL patients diagnosed between January, 2010 and December, 2015 were enrolled to this study. After validating previous definitions, the SCHOLAR-1 study was most suitable to define refractory DLBCL. The estimated 5-year cumulative incidence of refractory patients was 20% (95% confidence Interval [CI] = 18%-22%). After the determination of refractory disease, overall response rate and complete remission rate were 30% (95% CI = 22%-38%) and 9% (95% CI = 4%-15%), respectively. Patients with either no response to immunochemotherapy or relapse within 12 months after stem-cell transplantation had inferior survival with a median OS of 5.9 months (95% CI = 5.5-7.1 months) and 2-year OS rate of 16% (95% CI = 12%-20%). International prognostic index score 4-5 (hazard ratio [HR] = 2.22; 95% CI = 1.47-3.35), central nervous system relapse (HR = 1.43; 95% CI = 1.04-1.97), and best response status (HR = 2.68; 95% CI = 1.42-5.03 for partial remission. HR = 5.97, 95% CI = 3.21-11.11 for stable disease/progressive disease) were independent unfavorable prognostic factors.

Conclusions: This is the first large-scale Asian cohort study focusing on outcomes of refractory DLBCL. The definition of the SCHOLAR-1 study identifies patients with homogenously inferior survival, thus is appropriate to select refractory DLBCL. Due to poor clinical outcomes in the rituximab era, patients with refractory DLBCL may be potential candidates for novel treatment modalities.

Keywords: diffuse large B-cell lymphoma; immunochemotherapy; multicenter cohort study; prognosis; refractory; relapse; rituximab; treatment response.

FIGURE 1

Flow diagram of patients included in the REAL‐TREND dataset and refractory DLBCL dataset. Abbreviations: REAL‐TREND, REtrospective AnaLysis of Treatment REspoNse of refractory DLBCL; CR, complete remission; PR, partial remission; SD, stable disease; PD, progressive disease; SCT, stem cell transplantation; DLBCL, diffuse large B‐cell lymphoma

FIGURE 2

Validation of previous definitions of refractory DLBCL in the REAL‐TREND dataset. A. Overall survival of Definition 1 (Coiffier et al.). B. Overall survival of Definition 2 (Cheson et al.). C. Overall survival of Definition 3 (Hitz et al.). D. Overall survival of Definition 4 (SCHOLAR‐1). Abbreviations: CR, complete remission; PR, partial remission; SD, stable disease; PD, progressive disease; SCT, stem‐cell transplantation

FIGURE 3

Stratified analysis of the overall survival of refractory DLBCL. Overall survival is shown for subgroups by refractory IPI scores (A), subgroups by CNS relapse (B), subgroups by treatment modalities (C), and subgroups by best response after refractory disease (D). Abbreviations: IPI, international prognostic index; SCT, stem‐cell transplantation; CNS, central nervous system; CR, complete remission; PR, partial remission; SD, stable disease; PD, progressive disease.