P1128: evaluation of standard of care in second-line for patients with relapsed or refractory diffuse large b-cell lymphoma in the pre-car-t era: a dutch population-based study

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Outcomes of patients with diffuse large B-cell lymphoma (DLBCL) who are refractory to or who relapse early after first-line therapy (i.e., “early R/R” DLBCL) are generally poor. Second-line treatment options for early R/R DLBCL include salvage immunochemotherapy followed by autologous stem cell transplantation (ASCT) for younger, fit patients and non-intensive regimens for older and unfit patients. In 2022, the European Medicines Agency approved the first CAR T-cell therapy (axicabtagene ciloleucel; axi-cel) to treat adults with early R/R DLBCL based on the results of the pivotal phase 3 ZUMA-7 trial. ZUMA-7 showed the efficacy of axi-cel for early R/R DLBCL patients eligible for second-line therapy with intensive, potentially curative therapy. With the emergence of novel second-line treatment options, evaluating the standard of care (SoC) for early R/R DLBCL in a real-world setting is necessary. However, these data are hitherto scarce. Aims: As a benchmark for novel treatments, we evaluated population-based outcomes of SoC in second-line for early R/R DLBCL patients in the Netherlands in the pre-CAR-T era. Methods: We selected adult patients (≥18 years) with DLBCL, transformed follicular lymphoma (tFL), and primary mediastinal B-cell lymphoma (PMBCL) diagnosed between 2014-2018 from the nationwide Netherlands Cancer Registry. Three inclusion criteria were used and based on ZUMA-7: 1) first-line treatment with an anti-CD20 monoclonal antibody and an anthracycline, 2) early R/R disease defined as either stable/progressive disease as best response to first-line treatment or partial/complete response and subsequent relapse ≤12 months from completion of first-line treatment, and (3) second-line treatment with an intensive regimen ±ASCT. Patients who received CAR T-cell therapy were excluded. Descriptive statistics were used to analyze baseline characteristics at the start of second-line treatment. Survival was assessed from start of second-line treatment until progression, start of subsequent treatment, death, or end of follow-up, whichever occurs first (event-free survival, EFS), or until death or end of follow-up (overall survival, OS), using the Kaplan-Meier method. Results: Of the 6,899 adult patients diagnosed with DLBCL, tFL, and PMBCL in the Netherlands between 2014-2018, 527 received second-line treatment for early R/R disease. After excluding patients who received non-intensive regimens (n=186) and CAR T-cell therapy recipients (n=33), 308 patients were included in our cohort (median age: 60 years; 7% ≥70 years; 66% males; 61% stage III-IV, 90% DLBCL, 6% tFL, 4% PMBCL). In 36% (n=111/308) of the included patients the intensive regimen was followed by ASCT. For 266 patients, the best response to second-line treatment was available, with overall response and complete remission rates of 51% (n=157) and 32% (n=98), respectively. With ≥3 years of follow-up, the median EFS was 3.3 months (95% confidence interval [CI], 2.7-4.2), with a 2-year EFS rate of 27% (95% CI: 22-32; Figure 1A). The median OS was 7.1 months (95% CI: 6.3-8.7), with a 2-year OS rate of 32% (95% CI: 27-38; Figure 1B). Summary/Conclusion: This population-based study demonstrated that in the real world pre-CAR-T era the survival of early R/R DLBCL patients treated with second-line intensive therapy ±ASCT is poor, highlighting the need for novel treatments to improve outcomes. Real-world data on SoC and population estimates facilitate comparison of (cost-)effectiveness and budget impact of novel treatments with usual care in clinical practice and help to shape the future treatment landscape for early R/R DLBCL.Keywords: Diffuse large B cell lymphoma, Real world data, relapsed/refractory, Outcome