Bridging the CART gap: epcoritamab as a feasible option for relapsed/refractory DLBCL in CART-inaccessible regions - “the Argentine experience”

Abstract

Introduction. In the absence of CART, bispecific antibodies (BsAbs) emerged as a potential alternative for RR patients. BsAbs can offer a bridge to consolidation strategies (autologous/allogeneic-stem cell transplant (ASCT/Allo-SCT)). This study evaluated the utilization of epcoritamab in compassionate use requests before its approval in Argentina; assessed response rates, PFS, and overall survival (OS) in patients treated with epcoritamab, and compared outcomes in those who received consolidation therapies. Methods. 40 patients with RR-DLBCL who requested epcoritamab through the compassionate use program in Argentina were included. 28 patients were analyzed. 7 patients did not receive treatment due to disease progression. Data for 5 were not available. Results. 89% was diagnosed with DLBCL, predominantly NOS. Mean age was 57 ± 11 years. Most patients had advanced-stage disease (III/IV), many showing extranodal involvement. The mean of previous lines was 3 (range 2-5, including ASCT 29.6%). Patients received 1-15 cycles (C) of E (median 4.5), and 26/28 underwent PET-CT after C2 of E;19 showed response (CR/PR). 26/28 responded:15 achieving CR,8 before C4. Epcoritamab was used as a bridge to ASCT or Allo-SCT in 5 patients, with an OS rate of 100% among those who received Allo-SCT. The OS for all patients was 46.2% at 12.5 months. The OS increased to 66.7% at 12 months among responders, significantly higher than the 20% OS in non-responders. At 18 months of follow-up, OS was 50% and 0%, respectively. Consolidation with Allo-SCT resulted in an OS of 100% (p = 0.01), although the number of patients receiving ASCT was too small to make a meaningful comparison. Response to epcoritamab was independent of sex, number of prior treatments, or primary refractory status, but responders had significantly better survival outcomes (p=0.003). No significant association was found between response and the presence of cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS), though ICANS was linked to an increased risk of death (p=0.03). Regarding safety,39% of patients had CRS (most G1), and 18% had ICANS. 9 patients developed cytopenias, mostly mild, and 13 developed hypogammaglobulinemia. The mortality rate was 53.6%(disease progression (8/28), infections (6/28)). Hypogammaglobulinemia significantly increased the risk of death (p=0.001), and cytopenias showed near-statistical significance (p=0.05). Conclusion. The study’s cohort characteristics were similar to the EPCORE NHL-1 study, with the notable exception of no prior CART exposure. Epcoritamab demonstrated efficacy comparable to other studies, with encouraging survival outcomes in patients who responded to treatment. It also highlighted the potential of BsAbs as a bridge to consolidation with ASCT or Allo-SCT, achieving a 100% survival rate for those who received Allo-SCT. The use of BsAbs as a bridge to consolidation (mean 4 cycles) is a viable non-standard option for countries where their high costs make them unaffordable. Proper management of adverse events such as infections and hypogammaglobulinemia is crucial for improving safety and survival outcomes in these high-risk patients.