Epcoritamab Monotherapy for CLL Is Effective, Toxicity Reduction Possible

In relapsed or refractory chronic lymphocytic leukemia (CLL) with or without high-risk features, epcoritamab monotherapy brings favorable efficacy results. This is according to expansion cohort data from the EPCORE CLL‑1 phase Ib/II trial presented at the 66^th American Society of Hematology Annual Meeting and Exposition in San Diego, California.

“These findings provide evidence of efficacy and potential therapeutic applicability of epcoritamab in CLL and support its continued evaluation,” wrote lead author Alexey Danilov, MD, PhD, of City of Hope in Duarte, California.

Also presented at the Meeting were initial data from the trial’s cycle 1 optimization cohort. According to Dr. Danilov, the investigators saw in these data that “immune-related toxicities were markedly improved with an adapted step-up dose schedule, with primarily grade 1 [cytokine release syndrome (CRS)] and no [immune effector cell-associated neurotoxicity syndrome (ICANS)].”

This multicenter, open-label trial had a total cohort of 40 patients with CD20 positive relapsed or refractory CLL or small lymphocytic lymphoma, at least two prior systemic treatments, and failure or intolerance to a Bruton tyrosine kinase (BTK) inhibitor. The patients had a median age of 71.5 years, a median of four prior therapies, and 85% were double-exposed to BTK inhibitors and B-cell lymphoma 2 (BCL2) inhibitors. TP53 aberrations were present in 63% of the cohort and 70% of the cohort had unmutated IGHV.

All patients received subcutaneous epcoritamab 48 mg in 28-day cycles, increasing from once weekly, to every two weeks, to every four weeks over at least ten cycles. All patients received dexamethasone 15 mg as CRS prophylaxis.

The expansion cohort included 23 patients and had a median follow-up of 22.8 months. It had an overall response rate (ORR) of 61%, a complete response (CR) rate of 39%, median progression-free survival of 12.8 months, and an estimated 65% of patients were alive at 15 months. The ORR and CR rate in double-exposed patients was 53% and 37%, respectively, in patients with TP53 aberrations was 67% and 33%, and in patients with unmutated IGHV was 63% and 44%.

Regarding CRS in this cohort, grade 1 CRS occurred in 9% of patients, grade 2 in 70%, and grade 3 in 17%, with no treatment discontinuations due to CRS. ICANS occurred in three patients and clinical tumor lysis syndrome (CTLS) in one, none of which led to treatment discontinuation. There were four mortalities due to treatment-emergent adverse events (TEAEs).

The optimization cohort included 17 patients and had a median follow-up of 2.9 months. This cohort saw reduced CRS severity, with 71% of patients experiencing grade 1 CRS and 12% grade 2, with no treatment discontinuations due to CRS. There were no occurrences of ICANS, CTLS, or TEAE-based mortality in this cohort.

Reference

Danilov A, Fakhri B, Awan FT, et al. Epcoritamab monotherapy in patients (pts) with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL): Results from CLL expansion and optimization cohorts of EPCORE CLL-1. Abstract #883. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; December 7-10, 2024; San Diego, California.