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.

Survival among patients with relapsed/refractory diffuse large B cell lymphoma treated with single-agent selinexor in the SADAL study

“…These combination results are consistent with a significant anti-DLBCL contribution of selinexor to standard chemotherapy and are being further evaluated. Single-agent oral selinexor treatment was associated with a longer OS than expected based on contemporary case series [10][11][12] despite patient treatment, response history, age, and comorbidities. Given the beneficial impact of selinexor as a single agent and the poor prognosis of many patients, randomized studies of selinexor in combination with a variety of other anti-DLBCL agents are planned.…”

“…10 Cleveland Clinic, Cleveland, USA. 11 APHP, Hemato-oncology, Saint-Louis Hospital, Paris, France. 12…”

Zanubrutinib plus salvage chemotherapy for relapsed or refractory diffuse large B-cell lymphoma

“…Ibrutinib plus buparlisib (a pan-PI3K inhibitor) for 37 patients with R/R DLBCL achieved an ORR of 31% ( 21 ). In the REAL-TREND study ( 22 ), a real-world retrospective analysis of treatment response of R/R DLBCL from 8 centers in China (including our center), the pooled ORR of salvage chemotherapy was 30% and the CRR was 9%. Our results with high efficacy indicated that zanubrutinib may act synergistically with conventional chemotherapeutic regimens.…”

Construction of tandem diabody (IL-6/CD20)-secreting human umbilical cord mesenchymal stem cells and its experimental treatment on diffuse large B cell lymphoma

“…Theoretically, antibody-based therapy could eliminate all tumor cells; however, it is reported that 4-12% of patients who received the rituximab-based therapy experienced primarily refractory and 17-40% relapse after complete remission (CR) or partial remission (PR). Moreover, 12-60% of these patients experience tumor recurrence after the second-or third-line therapy [2][3][4]27]. The resistance mechanisms of rituximab remain elusive, which might be associated with tumor microenvironment (TME), host immunologic factors, pharmacokinetics, downregulation or loss of CD20 [26,28].…”