COMPARATIVE EFFECTIVENESS OF SALVAGE CHEMOTHERAPY AND CHIMERIC ANTIGEN T‐CELL RECEPTOR THERAPIES IN R/R DLBCL: A SYSTEMATIC REVIEW AND NETWORK META‐ANALYSIS

Abstract

David Hodgson and John Kuruvilla are co-senior investigators Introduction: The optimal salvage chemotherapy (SC) regimen for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) prior to autologous stem cell transplant (ASCT) remains unclear. Head-to-head comparison of chimeric antigen receptor T cell (CAR-T) therapies for second line use in primary refractory DLBCL is lacking. Given these limitations, we conducted a systematic review and network meta-analysis (NMA) of randomized clinical trials (RCTs) to assess the efficacy and safety of SC and CAR-T therapies for R/R DLBCL. Methods: We searched MEDLINE, EMBASE and CENTRAL from Jan 1 2006 to July 7 2022 for RCTs enrolling patients diagnosed with R/R DLBCL following treatment (trt) with at least 1 prior regimen. The primary outcome was overall survival (OS), and secondary outcomes were progression free survival (PFS) and grade ≥ 3 adverse events (AEs). NMA was conducted using a fixed-effect model to synthesize evidence. Surface under the cumulative ranking curve was used to rank the relative effect of compared trt. Results: A total of 22 RCTs (n=4505) met eligibility criteria, 13 included for qualitative synthesis only. NMA of SC (6 RCTs, n=1831) compared 7 trt: GDP (gemcitabine, dexamethasone, cisplatin), rituximab (R)-GDP, ICE (ifosfamide, mesna, carboplatin, etoposide), R-ICE, DHAP (dexamethasone, cytarabine, cisplatin), R-DHAP, ofatumumab (O)-DHAP, ESHAP (etoposide, cytarabine, cisplatin, methylprednisolone). Results indicated that R-GDP had improved OS and PFS over other regimens (Table), and ranked highest for OS and PFS. NMA of AEs showed no differences for infection. NMA of 3 CAR-T RCTs (axi-cel, liso-cel, tisa-cel; n=733) showed that axi-cel and liso-cel had improved PFS over SC and ASCT, while no OS difference was observed. Comparing between CAR-T products, both axi-cel and liso-cel had improved OS and PFS over tisa-cel. Liso-cel ranked highest for PFS. NMA of AEs showed that tisa-cel and axi-cel had higher risk of cytokine release syndrome over SC, while axi-cel had higher risk of neurologic toxicity over SC. Conclusions: Our results suggest that R-GDP may be the optimal regimen for R/R DLBCL prior to ASCT. Both axi-cel and liso-cel had improved PFS over SC and ASCT, while tisa-cel did not. Although liso-cel ranked highest for PFS, longer follow-up is required for comparative survival analysis as data matures. Keywords: Aggressive B-cell non-Hodgkin lymphoma, Therapeutics and Clinical Trials in Lymphoma - Other No conflicts of interests pertinent to the abstract.