Outcomes of relapsed/refractory diffuse large B-cell lymphoma and influence of chimaeric antigen receptor T trial eligibility criteria in second line-A population-based study of 736 patients

Abstract

Several recently published trials investigate novel therapies for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). To estimate the benefit of these therapies in the real-world setting, comprehensive data on patients treated in clinical routine are needed. We report outcomes for 736 R/R DLBCL patients identified among all curatively treated DLBCL patients in Sweden in the period 2007-2014. Survival and associations with disease characteristics, second-line treatment and fulfilment of chimaeric antigen receptor (CAR) T-cell trial criteria were assessed. Median overall survival (OS) was 6.6 months (≤70 years 9.6 months, >70 years 4.9 months). Early relapse (≤12 months) was strongly associated with selection of less intensive treatment and poor survival. Among patients of at most 70 years of age, 63% started intensive second-line treatment and 34% received autologous stem cell transplantation (ASCT). Two-year OS among transplanted patients was 56% (early relapse ≤12 months 40%, late relapse >12 months 66%). A minority of patients 76 years (n = 178/506, 35%) fitted CAR T trial criteria. Median progression-free survival (PFS) for patients with early relapse fitting trial criteria was 4.8 months. In conclusion, most R/R DLBCL manifest early and are often ineligible for or cannot complete intensive regimens resulting in dismal survival. Real-world patients eligible for CAR T trials also did poorly, providing a benchmark for efficacy of novel therapies.

Keywords: clinical research; epidemiology; non-Hodgkin lymphoma; stem cell transplantation; tumour immunotherapy.

FIGURE 1

Overall survival among all relapsed/refractory diffuse large B‐cell lymphoma patients (R/R DLBCL) (n = 736). (A) Stratified by age of at most 70 and older than 70 years at relapse. (B) Stratified by time to first relapse. (C) Stratified by secondary IPI score. * (D) Stratified by cell of origin. ** GCB, germinal centre B; IPI, international prognostic index. *, Based on age, stage, Eastern Cooperative Oncology Group performance status, lactate dehydrogenase level and number of extranodal sites at time of relapse/refractoriness. **, Information regarding cell of origin was based on immunohistochemistry mostly from primary diagnosis and categorized using the Hans algorithm

FIGURE 2

Disease characteristics and probability of receiving intensive second‐line treatment and going through autologous stem cell transplantation. (A) Associations between disease characteristics and probability of receiving intensive second‐line treatment among patients with relapsed/refractory diffuse large B‐cell lymphoma (R/R DLBCL) of at most 70 years of age, estimated using multivariable logistic regression [odds ratios and 95% confidence intervals (CI)]. (B) Associations between disease characteristics and probability of going through ASCT after intensive treatment, among patients with relapsed/refractory diffuse large B‐cell lymphoma (R/R DLBCL) of at most 70 years of age, estimated using Cox regression (hazard ratios, 95% CI). CCI, Charlson comorbidity index; ECOG, Eastern Cooperative Oncology Group; IPI, international prognostic index; LDH, lactate dehydrogenase

FIGURE 3

Proportion of patients with relapsed/refractory diffuse large B‐cell lymphoma (R/R DLBCL) of at most 70 years of age who received autologous stem cell transplantation (ASCT). (A) Among all patients. (B) Among patients with age under 60 years at relapse. (C) Among patients with age 60–70 years at relapse. (D) Among patients with relapse within 12 months. (E) Among patients with relapse later than 12 months. Proportions were estimated in the presence of the competing risk of death as first event. CI, confidence interval

FIGURE 4

Overall survival (OS) for all relapsed/refractory diffuse large B‐cell lymphoma (R/R DLBCL) patients of at most 70 years at relapse who underwent autologous stem cell transplantation (ASCT). (A) Among all patients. (B) Among patients with early relapse (≤12 months from primary diagnosis) and late relapse (>12 months) separately. (C) Among patients aged less than 60 or 60–70 years separately. Patients were followed from date of ASCT until death of any cause

FIGURE 5

Progression‐free survival among all relapsed/refractory diffuse large B‐cell lymphoma (R/R DLBCL) patients of 76 years of age or younger who received any intravenous (IV) second‐line treatment (i.e. received at least 2 treatment lines) and among those who fulfilled chimaeric antigen receptor (CAR) T‐cell trial criteria. (A) Among all patients of at most 76 years who received at least two treatment lines (solid line) and among those who fulfilled CAR T‐cell trial criteria (dashed line). (B) Among patients of at most 70 years with early relapse. (C) Among patients of 71–76 years with early relapse. (D) Among all patients of at most 76 years who received at least two treatment lines (solid line) and among those who fulfilled CAR T‐cell trial criteria (dashed line). (E) Among patients of 71–76 years with late relapse. (F) Among patients of 71–76 years with late relapse.