Characteristics and Treatment Patterns of Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma Who Received ≥3 Lines of Therapies

Introduction: Treatment options continued to evolve in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), with many novel treatments available in recent years. The current study aimed to describe characteristics and treatment patterns of patients with R/R DLBCL who received ≥3 lines of therapy (LOT) using recent real-world data.

Methods: This study used the PharMetrics Plus administrative claims database to identify adult patients who had ≥1 inpatient claim or ≥2 outpatient claims for DLBCL (ICD-10: C83.3) between 10/01/2015 and 09/30/2019. Patients were selected if they had ≥6-months of continuous eligibility before the first DLBCL diagnosis (index diagnosis). To capture newly diagnosed patients, the study excluded patients who had a claim for a possible DLBCL diagnosis and other hematologic malignancies (except hematologic conditions that may transform into DLBCL) before the index diagnosis and those who had stem cell transplantation (SCT) as the first treatment without prior chemotherapy (CT). An algorithm was developed to define LOT. In general, a new LOT was indicated by addition of a new drug or re-initiation of the previous LOT after a gap of ≥90 days. Pharmacologic therapies were categorized as CT or chemoimmunotherapy (CIT) or novel agent-based therapy (including brentuximab vedotin, ibrutinib, venetoclax, lenalidomide, obinutuzumab, nivolumab and pembrolizumab). SCT was counted as consolidation therapy instead of a separate line, while chimeric antigen receptor T cells (CAR-T) was counted as a separate line with preparation included (e.g., leukapheresis, bridging therapy, and lymphodepletion). Patients who received a third LOT (3L) comprised the study population, with the index date defined as the initiation date of 3L pharmacologic therapy or the infusion date of 3L SCT or CAR-T. 3L treatment distribution was described separately before and after the first CAR-T approval for DLBCL (10/18/2017). Treatment duration of 3L pharmacologic therapies was analyzed using Kaplan-Meier (KM) analysis. The proportion of patients initiating 4L during the observed follow-up period were described for all patients receiving a 3L. Due to the limited follow-up time and a high proportion of censoring, the current data was not mature to estimate rates of 4L initiation at different time points based on the KM analysis. All analyses were conducted for the overall study population and by treatment.

Results: Among the 3,559 DLBCL patients receiving ≥1L treatment, 92.3% were treated with rituximab-containing regimens and 68.9% with R-CHOP or similar in 1L. There were 160 (4.5%) patients who received ≥3 LOT, with a mean age of 58.5 years and 64.4% male. Before CAR-T approval, 51 patients received 3L: 52.9% received CT/CIT, 33.3% received novel agent-based therapy, and 13.7% received SCT. After CAR-T approval, 109 patients received 3L: 45.9%, 30.3%, 7.3%, and 16.5% received CT/CIT, novel agent-based therapy, SCT and CAR-T, respectively. There were some differences in patient characteristics across treatment groups. Specifically, CAR-T patients had a relatively lower mean Charlson Comorbidity Index (CCI) score (2.9). The novel therapy group had a shorter median time from index diagnosis to index date (10.3 months). SCT patients were younger (mean 56.6 years) but with a relatively higher mean CCI score (4.2). The median follow-up time was 5.0 months and varied across treatments: from 3.9 months for CAR-T to 5.7 months for SCT. Among patients receiving pharmacologic treatments, the median treatment duration was 3.1 months and 2.8 months for the CT/CIT and novel agent-based therapy groups, respectively. During a median follow-up time of <6 months, a total of 51 (31.9%) patients initiated 4L. The proportion was 27.8% in the CAR-T group, 28.6% in the CT/CIT group, 38.0% in the novel therapy group and 33.3% in the SCT group.

Conclusions: In patients with R/R DLBCL receiving 3L treatment post CAR-T approval, about 76% were treated with CT/CIT or novel agent-based therapies, though most of the novel agents are not indicated for DLBCL. CAR-T and SCT were used in 17% and 7% of patients, respectively. Treatment duration of 3L CT/CIT or novel agent-based therapies was short. A relatively high proportion of patients moved to the next LOT during a short follow-up period. These findings highlight the unmet need for more effective treatments among R/R DLBCL patients in 3L and later lines.