Epcoritamab Plus R-CHOP Shows Efficacy and Tolerance as First-Line Treatment for High-Risk DLBCL

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Addition of subcutaneous epcoritamab to standard-of-care R-CHOP demonstrated clinically meaningful response in first-line treatment of patients with high-risk diffuse large B-cell lymphoma according to updated results of a single arm of the EPCORE NHL- 2 trial.

The addition of subcutaneous epcoritamab to standard therapy R-CHOP demonstrated a clinically meaningful response in the first-line treatment of patients with high-risk diffuse large B-cell lymphoma (DLBCL) according to reported results. single-arm update of the EPCORE NHL-2 trial (NCT04663347), presented at the 2022 AASCO Annual Meeting.

At a median follow-up of 6.9 months (range: 0.8-14.7), the overall response rate among the 33 treated patients was 100%, comprising a complete metabolic response rate of 77% and a metabolic response 23% partial. As of the March 25, 2022 data close, 73% of patients remained on treatment and only 2 discontinued due to active disease.

In the study arm, patients with previously untreated DLBCL received subcutaneous epcoritamab and standard therapy R-CHOP (rituximab [Rituxan] plus cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone) for six 21-day cycles, followed by epcoritamab monotherapy for 1 year. The median duration of treatment was 6.3 months (range: 0.6-11.5) and 91% of patients completed 6 cycles of R-CHOP.

“This drug is well suited for combination therapy due to its mechanism of action, which is distinct from that of the R-CHOP standard of care components,” Lorenzo Falchi, MD, medical oncologist at Memorial Sloan Kettering Cancer Center in New York, New York, said during the data presentation. Epcoritamab’s mechanism of action and safety profile differ from standard treatments, and epcoritamab is well suited for combination use and in first-line treatment, according to the study researchers.

Eligible patients had a newly diagnosed CD20 positive DLBCL, an International Prognostic Index score of 3 or greater, and an ECOG performance status of 0 to 2. The median age was 66 years (range, 19-82) and the majority (55%) were men.

“Notably, more than 20% of the cohort had double or triple impact lymphoma,” Falchi said. Specifically, 9% had double impact lymphoma and 15% had triple impact lymphoma.

During the dose escalation portion (n=10), 4 patients received subcutaneous epcoritamab 24 mg and 6 patients received epcoritamab 48 mg, in combination with R-CHOP for cycles 1 through 6. In this portion of the study, the primary endpoints were toxicity/safety and dose-limiting tolerability and the secondary endpoint was antitumor activity.

In the dose extension portion (n=23), patients received 48 mg epcoritamab plus R-CHOP; the primary objective was antitumor activity.

The median follow-up was 6.9 months (range, 0.8-14.7) and patients received a median of 9 treatment cycles. Seventy-three percent of patients continue to receive treatment, 18% have stopped treatment and 9% have completed treatment.

Treatment-emergent adverse events (TEAEs) in ≥20% of patients were anemia (60%), neutropenia (60%), cytokine release syndrome (CRS; 51%), d-site reaction injection (42%), nausea (45%), constipation (33%) and pyrexia (33%).

Investigators noted that discontinuation of treatment was observed in 18% of patients. AEs of particular interest included CRS grade 1/2 (48%), CRS grade 3 (3%) and immune effector cell-associated neurotoxicity syndrome grade 2 (3%), which resolved in 4 days. Most CRS events occurred during the first cycle and resolved after a median of 2 days (range, 1-4). Five patients (15%) with CRS received tocilizumab (Actemra).

R-CHOP remains the mainstay of treatment and can provide long-term disease control in up to 90% of patients with limited-stage disease and up to 60% of those with advanced disease. Historically, patients with high-risk DLBCL have had poor outcomes with an overall 4-year survival rate of 55% when treated with the current standard treatment.2,3 Epcoritamab binds to CD3 on T cells and CD20 on B cells to induce T cell – mediated destruction of CD20+ B cells. New therapies like this could potentially improve outcomes for patients with high-risk disease.

This updated dataset with longer follow-up shows promising response rates and a safety profile with no new safety signals detected, the investigators wrote.

“It is important to note that the majority of CRS events were low grade and did not lead to treatment discontinuation. These results support further evaluation of epcoritamab in combination with R-CHOP in this population,” Falchi concluded.

References

  1. Falchi L, Offner F, Belada D, et al. First-line (Tx) treatment with subcutaneous (SC) epcoritamab (epco) + R-CHOP in patients (pts) with high-risk diffuse large B-cell lymphoma (DLBCL): evidence update phase 1/2. J Clin Oncol. 2022;40(supplement 16):7523. doi:10.1200/JCO.2022.40.16_suppl.7523
  2. Sehn LH, Berry B, Chhanabhai M, et al. The Revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP. Blood. 2007;109(5):1857-1861. doi:10.1182/blood-2006-08-038257
  3. Susanibar-Adaniya S, Barta SK. 2021 update on diffuse large B-cell lymphoma: a review of current evidence and potential applications in risk stratification and management. Am J Hematol. 2021;96(5):617-629. doi:10.1002/ajh.26151

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