CML

RT is the transformation of chronic lymphocytic leukemia (CLL) into CD20+ diffuse large B-cell lymphoma (DLBCL), with poor prognosis exacerbated by prior CLL treatments and TP53 aberrations. Current chemoimmunotherapy (CIT) yields low complete response (CR) rates (≤20%). Epcoritamab, a subcutaneous CD3xCD20 bispecific antibody, is approved for relapsed or refractory large B-cell lymphoma. The ongoing EPCORE™ CLL​1 trial (NCT04623541) evaluates its safety and efficacy in RT. Preliminary results show promising efficacy and manageable safety.

Arnon P. Kater and the team aimed to assess the safety and efficacy of epcoritamab monotherapy in patients with Richter’s transformation (RT).

They performed an inclusive analysis of adults with biopsy-proven transformation to CD20+ DLBCL and a clinical history of CLL or small lymphocytic lymphoma. Patients with ≤2 prior lines of treatment for RT received epcoritamab 48 mg in 28-day cycles (QW, C1–3; Q2W, C4–9; Q4W, C≥10) until disease progression. To mitigate cytokine release syndrome (CRS), step-up dosing and corticosteroid prophylaxis were required in C1. Response was assessed using PET-CT per Lugano classification.

About 35 patients with RT had received epcoritamab as of October 5, 2023 (median follow-up of 8.1 months). A total of 91% of patients had ≥1 prior treatment line for CLL or RT, and 49% had prior treatment for RT. Most patients (57%) had received a Bruton’s tyrosine kinase or B-cell lymphoma 2 inhibitor prior to transformation, reflecting current treatment for CLL. The most common prior treatment for RT was an anti-CD20 monoclonal antibody-containing CIT regimen, primarily R-CHOP (in 76% of patients with prior treatment). As of data cutoff, 13 patients (37%) were still receiving epcoritamab.

In the response-evaluable population (n=26), the overall response rate (ORR) was 50%, and the complete response (CR) rate was 35%. Median times to response and CR were short (1.4 months and 2.4 months, respectively), and an estimated 53% of patients with CR remained in CR at 9 months (75% among patients with CR without prior treatment for RT). The most common nonhematologic treatment-emergent adverse event (TEAE) was cytokine release syndrome (CRS) (80%). Thrombocytopenia and anemia were observed in 40% of patients each at baseline and in 40% and 34% of patients, respectively, during the study per iwCLL criteria. CRS events primarily occurred following the first full dose, and most were low grade; only 1 patient (3%) had Grade 3 CRS.

Four patients had immune effector cell-associated neurotoxicity syndrome (ICANS) (Grade 1, n=2; Grade 2, n=2); all 4 patients had concurrent CRS. Clinical tumor lysis syndrome (CTLS) occurred in 3 patients (Grade 1–3, n=1 each). No CRS, ICANS, or CTLS events led to treatment discontinuation. Two patients discontinued treatment due to adverse events (AEs), and 3 patients had fatal TEAEs (general physical health deterioration [n=2] and sepsis). Data for all patients (N=42) from the fully enrolled cohort will be presented.

The study concluded that the first disclosure of data from a large RT cohort, now fully enrolled and with longer follow-up, demonstrates that epcoritamab treatment leads to encouraging ORR and CR rates in a high-risk population of patients with RT, with notably higher response rates in previously untreated RT. Safety was tolerable and consistent with prior reports; most CRS was low grade, and no new safety signals were observed.

Efforts to further mitigate CRS with C1 optimization, including an additional step-up dose of epcoritamab, are ongoing. These highly encouraging data support further evaluation of epcoritamab as a chemotherapy-free treatment option for patients with RT.

The trial was sponsored by the Genmab.

Source: https://library.ehaweb.org/eha/2024/eha2024-congress/422267/arnon.p.kater.single-agent.epcoritamab.leads.to.deep.responses.in.patients.html?f=menu%3D6%2Abrowseby%3D8%2Asortby%3D2%2Ace_id%3D2552%2Aot_id%3D29194%2Amarker%3D5099%2Afeatured%3D18527

Clinical Trial: https://clinicaltrials.gov/study/NCT04623541

Kater A.P., Janssens A, Eradat H, et al. (2024). “SINGLE-AGENT EPCORITAMAB LEADS TO DEEP RESPONSES IN PATIENTS(PTS) WITH RICHTER’S TRANSFORMATION (RT): PRIMARY RESULTS FROMTHE EPCORE CLL-1 TRIAL.” Presented at EHA 2024.