Positive Outcomes of Novel Cellular Therapies Are Seen in Long Relapse, DLBCL

In a real-world study, patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who would benefit most from novel therapies vs patients who would likely do well with standard treatment were identified among all curatively treated patients in Sweden from 2007 to 2014. The objective of the study was to estimate the benefit of these novel therapies.

Investigators reported that median overall survival (OS) was 6.6 months in a large population-based cohort of 736 patients with R/R DLBCL who were registered in the national Swedish Lymphoma Registry. Median progression-free survival (PFS) for all patients was 3.9 months (95% CI, 3.5-4.6).

In a subgroup analysis, patients younger than 70 years (n = 220) had a median OS of 9.6 months (95% CI, 8.0-11.8) with a 2-year OS rate of 35% (95% CI, 30%-40%). In patients over 70 years of age, median OS was 4.9 months (95% CI, 4.1-5.7) and the 2-year OS rate was 19% (95% CI, 16%-23%), according to investigators.

In Sweden, all residents have access to specialized health care in oncology and hematology. The standard treatment for patients with R/R DLBCL who are younger than 70 years is platinum-based chemotherapy with the goal of consolidation with autologous stem cell transplantation (ASCT). For patients older than 70 years, the standard of care consists of remission-inducing chemotherapy or palliative treatment depending on performance status and comorbidities.

Investigators reported that the median age of patients was 71 years (range, 18-99) and 60% of patients were men. Relapse occurred in 62% of patients within 12 months of the primary diagnosis (n = 457), and 208 patients had primary refractory disease (28%). The majority (57%) of patients had stage IV disease.

When investigators stratified by time from primary diagnosis to R/R disease, the 2-year OS rate ranged from 19% (95% CI, 14%-24%) for patients with R/R disease within 6 months to 55% (95% CI, 47%-63%) for patients who relapsed after more than 2 years. For patients with primary refractory disease, the median OS was 4.4 months (95% CI, 3.8-5.0) and the 2-year OS rate was 14% (95% CI, 10%-19%).

Sixty-nine percent of patients were eligible to enroll in a chimeric antigen receptor (CAR) T-cell clinical trial with age limits set at 18 to 76 years (n = 506). In this group, 379 patients (75% of all ≤ 76 years) started an IV second-line therapy, of whom 178 patients (35% of all ≤ 76 years) also fulfilled the selected trial inclusion and exclusion criteria. For patients younger than 76 years with relapsed disease who fit the trial criteria, PFS was determined as 4.8 months, and 3.1 months for all patients who started any IV second-line treatment.

Patients with primary refractory disease had a 2-year survival rate of 14% compared with 66% in patients younger than 70 years with late relapse who were treated with intensive second-line therapy and ASCT.

When reviewing eligibility criteria for CAR T therapy in the second-line setting, investigators reported that clear PFS benefit was not associated in patients over 76 years of age with early relapse. They noted that this was particularly important when determining the value of CAR T therapies in the broader real-world setting.

The investigators confirmed a strong association between short time to relapse and low probability of receiving standard second-line therapy and ASCT among patients 70 years or younger, and short survival for all ages.

The study’s strengths include its large sample size and population-based design. Because this was a retrospective study, data were collected based on medical charts, which could have had missing information.

The investigators concluded that their findings provided evidence for the heterogeneity in tolerance and outcomes associated with second-line regimens and good standard-care outcomes among young patients in relapse. They noted the lack of outcome benefit for cellular therapies in patients who experienced early relapse and who were older.

REFERENCE

Harrysson S, Eloranta S, Ekberg S, et al. Outcomes of relapsed/refractory diff use large B-cell lymphoma and influence of chimaeric antigen receptor T trial eligibility criteria in second line–a population-based study of 736 patients. Br J Haematol. Published online April 25, 2022. © adventtr / istock.com 2022;10.1111/bjh.18197