Background: Progressive disease following chimeric antigen receptor T-cell (CAR-T) therapy for diffuse large B-cell lymphomas (DLBCL) is a common scenario. There are limited treatment options after CAR-T failure with a poor prognosis for patients at this stage in their disease. The effectiveness of existing treatment options following CAR-T failure is still being investigated in the real-world setting.
Aims: To further understand the clinical outcomes of CAR-T failure in relapse/refractory (RR) DLBCL patients in the real-world setting.
Methods: This retrospective analysis identified adult patients diagnosed with RR-DLBCL [01/01/2014 – 03/31/2021] who received CAR-T therapy and experienced a subsequent disease progression or death. COTA’s Real World Evidence (RWE) database is comprised of longitudinal, HIPAA-compliant data abstracted from electronic health records (EHR) from over 200 sites of care in US (60% academic, 40% community). The first post CAR-T therapy was categorized as checkpoint inhibitor +/- other therapies (CPI), investigational therapies, tafasitamab +/- lenalidomide, polatuzumab-containing regimen (pola-containing), lenalidomide +/- anti-CD20, BTK inhibitors (BTKi), chemotherapy/chemoimmunotherapy (CT/CIT), allogenic stem-cell transplant (allo-SCT), or anti-CD20 monoclonal antibody. Overall response rate (ORR), complete response (CR), and overall survival (OS) were reported for treatment groups with at least 5 patients.
Results: Of the 97 CAR-T patients identified, 57 (59%) patients failed CAR-T therapy due to receiving subsequent line of therapy, having documented progression event, or death. Patients who failed CAR-T were 67% male and on average 59 years old. Within a median follow-up of 12.4mo, 44 (77%) initiated further therapy whereby 7 (16%) initiated investigational therapies, 9 (20%) CPI, 7 (16%) tafasitamab +/- lenalidomide, 6 (14%) pola-containing, 5 (11%) lenalidomide +/- anti-CD20, 3 (7%) CT/CIT, 3 (7%) anti-CD20 monoclonal antibody, 2 (5%) BTKi, and 2 (5%) allo-SCT as their first post CAR-T therapy. Of these patients, 48% received more than two lines of therapies after CAR-T. Response rates of select first therapies received after CAR-T are detailed in Table 1. Outside clinical trials, ORR and CRs were highest for lenalidomide +/- anti CD20 (60% & 20%), followed by CPI (33% & 0%), pola-containing (33% & 0%) and tafasitamab +/- lenalidomide (14% & 0%). OS of first post CAR-T therapy was highest for lenalidomide+/- anti CD20 (12.5 mo), then CPI (11 mo), pola-containing therapy (6.37 mo), and tafasitamab +/- lenalidomide (2.7 mo).
Image:
Summary/Conclusion: There is no existing standard of care after patients fail CAR-T therapy. Although further research is warranted in a larger sample population, poor clinical outcomes in treatment response and longevity were observed with existing treatment options. There is still a high unmet need for more effective therapies after CAR T-cell therapy has failed.
