Results: As of May 28, 2024, 23 pts in EXP and 17 pts in OPT had received epcoritamab (median follow-up, 22.8 and 2.9 mo, respectively). Baseline characteristics were similar between cohorts, and across all 40 pts, median age was 71.5 y, median number of prior tx lines was 4 (range, 2-10), and median time from initial diagnosis to first epcoritamab dose was 11.6 y. All pts had prior BTKi, 88% had prior chemoimmunotherapy, and most had high-risk disease characteristics (TP53 aberrations, 63%; unmutated IGHV, 70%) and were double exposed to BTKi and BCL2i (85%). In EXP, ORR was 61% and CR rate was 39%. Median time to response was 2.0 mo and median time to CR was 5.6 mo. ORR/CR rate was 67%/33% among pts with TP53 aberrations (n=15), 63%/44% among pts with IGHV-unmutated disease (n=16), and 53%/37% among double-exposed pts (n=19). Among all pts in EXP, median progression-free survival was 12.8 mo and median OS was not reached, with an estimated 65% of pts remaining alive at 15 mo. Among 12 responders evaluable for minimal residual disease (MRD) by next-generation sequencing in peripheral blood, 9 (75%) had undetectable MRD (uMRD) at the standard 10−4 cutoff and 8 (67%) had uMRD at 10−6.
The most frequent nonhematologic tx-emergent AEs (TEAEs) in EXP were CRS (96%), diarrhea (48%), peripheral edema (48%), fatigue (43%), and injection-site reaction (43%). Cytopenias were common (anemia, 65%; thrombocytopenia, 65%; neutropenia, 48%); however, most pts had baseline anemia and thrombocytopenia, indicating that these AEs are disease related. Four fatal TEAEs occurred in EXP (pneumonia [n=2], sepsis [n=1], and squamous cell carcinoma of the skin [n=1]). No fatal TEAEs occurred in OPT. In EXP, CRS was manageable and primarily low grade (G; 9% G1, 70% G2, 17% G3); in OPT, CRS severity was substantially reduced, with only low-grade events (71% G1, 12% G2). In both cohorts, CRS events primarily occurred following the first full dose, and none led to tx discontinuation. In EXP, 3 ICANS events (G1, n=1; G2, n=2) and 1 CTLS event (G2) were reported; none led to tx discontinuation. No ICANS or CTLS occurred in OPT. Consistent with the reduced CRS severity in OPT, median IL-6 levels 24 h after the first full dose were markedly lower in OPT vs EXP.
Conclusions: Single-agent epcoritamab led to encouraging CR and uMRD rates in heavily pretreated R/R CLL, regardless of high-risk features. Immune-related toxicities were markedly improved with an adapted SUD schedule, with primarily G1 CRS and no ICANS. These findings provide evidence of efficacy and potential therapeutic applicability of epcoritamab in CLL and support its continued evaluation.
