DISCUSSION
tumor, LBCL, CRS, aggressive disease, DLBCL, non-Hodgkin lymphomas
B-CELL NON-HODGKIN LYMPHOMA, DISEASE PROGRESSION, TUMOR, REMISSIONS, FOLLICULAR LYMPHOMA, DISEASE, EVENT, NON-HODGKIN LYMPHOMA, EVENTS
Subcutaneous epcoritamab achieved rapid, deep, and durable responses, including CRs and MRD negativity, in this cohort of patients with challenging-to-treat and highly refractory LBCL. Overall response and CR rates were 63.1% (95% CI, 55.0 to 70.6) and 38.9% (95% CI, 31.2 to 46.9), respectively. Responses were primarily observed early, by either the first or the second response assessment (scheduled at weeks 6 and 12). Among complete responders, mDOR was not reached at the time of analysis. Median PFS was not reached in complete responders, and median OS was not reached at the time of analysis. As of the data cutoff date, 32.5% of patients continued to receive study treatment and 56.1% continued into the follow-up period. This cohort represents a heavily pretreated, heterogeneous patient population. Patients had a median of three prior lines of therapy at a median of 19 months from diagnosis: 61.1% had primary refractory disease, 28.8% with DLBCL had transformed DLBCL, and 38.9% had received prior CAR T-cell therapy, 75.4% of whom were refractory to CAR T-cell therapy. The aggressive disease of this patient population was further demonstrated in that 36 patients had disease progression (n = 28) or died (n = 8) within the first 6 weeks. Responses to epcoritamab were consistent across several prespecified subgroups, including age, line of therapy, primary refractory disease, and prior exposure to CAR T-cell therapy. Forty-nine (45.8%) of 107 patients were MRD-negative per circulating tumor DNA analysis, with most (an estimated 78.7%) remaining MRD-negative after 6 months. Furthermore, MRD negativity was associated with longer PFS, highlighting the depth and durability of response to continuous epcoritamab treatment.The safety profile of epcoritamab was consistent with previous reports. Notably, the majority of AEs occurred early (ie, in the first 12 weeks) in the treatment course. CRS, observed in 78 (49.7%) patients, was mostly low grade, predictable in terms of timing, and resolved. CRS occurred most frequently after the first full epcoritamab dose; tocilizumab was used to manage CRS in 22 of 78 (28.2%) patients. ICANS events were limited to mostly grade 1, and all resolved apart from the one fatal ICANS event in a patient with several confounding factors.Results observed with epcoritamab in patients with relapsed or refractory LBCL favorably compare with those observed in approved antilymphoma immunotherapies, although differences in patient populations and study designs should be considered. CAR T-cell therapies (axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel) demonstrated high ORRs (52%-82%) and CR rates (40%-54%) in phase I/II studies.CD3xCD20 bispecific antibodies are a treatment modality being developed for treatment of non-Hodgkin lymphomas, with one compound approved in the European Union for relapsed or refractory follicular lymphoma.Given the lack of direct comparison, there are currently no data to suggest whether the best outcome for heavily pretreated patients can be achieved by treating until disease progression or by stopping after a fixed number of treatment cycles. Treatment until progression ensures ongoing anti-CD20–directed, T-cell–mediated tumor suppression/surveillance. Continuation of subcutaneous epcoritamab at reduced frequency in later cycles may provide the greatest chance of durable remissions with limited burden for patients, but further studies would be helpful to determine the best treatment duration strategy for patients who achieve a CR. In this study, epcoritamab led to patient-reported improvements in their lymphoma-related symptoms and overall quality of life while receiving therapy. One limitation of our study is that it was a single-arm design with no control group for comparison.Single-agent epcoritamab demonstrated a high ORR, including deep and durable CRs, in a challenging-to-treat and highly refractory patient population with relapsed or refractory LBCL. Efficacy was consistent across key subgroups. Epcoritamab was mostly well tolerated, with few discontinuations because of AEs. CRS was manageable, with predictable timing, and was mostly grade 1 or 2. As long-term treatment, epcoritamab is administered on a once monthly basis as a subcutaneous injection, making it an attractive and convenient off-the-shelf alternative to other antilymphoma immunotherapies. These results support ongoing and future clinical trials of epcoritamab both as monotherapy and in combination in late and earlier lines of treatment for B-cell non-Hodgkin lymphoma.