Treatment Effective Before CAR T

SAN DIEGO — Single-agent epcoritamab demonstrated deep and durable responses in CAR T–naïve patients with relapsed or refractory large B-cell lymphoma (R/R LBCL) in a subgroup analysis of the pivotal phase 2 Epcore NHL-1 trial.

These findings show that epcoritamab — a bispecific antibody therapy available off the shelf and shown in the overall R/R LBCL population in Epcore NHL-1 to be effective following CAR T–cell therapy — can also be administered safely and effectively before CAR T in patients with R/R LBCL.

This is of particular note for patients who may be ineligible for CAR T or whose access to CAR T is limited, first author Yasmin H. Karimi, MD, said in an interview during a poster presentation at the annual American Society of Hematology (ASH) conference. 

With over 3 years of follow-up, epcoritamab monotherapy was associated with an overall response rate and complete response rate of 61% and 45%, respectively, in 96 CAR T-naïve patients, and side effects were manageable, said Karimi, of the University of Michigan, Ann Arbor, Michigan.

In Epcore NHL-1, epcoritamab — a CD3xCD20 T-cell-engaging bispecific antibody — led to deep and durable responses with manageable toxicity in the patients with R/R LBCL including both CAR T–treated and CAR T–naïve patients. The agent was subsequently approved for the treatment of adults with different types of R/R LBCL and follicular lymphoma after at least two prior lines of therapy. Among those who had received CAR T–cell therapy, the ORR/CR rates were 54% and 34%, according to results reported at ASH 2022.

Patients included in the trial were adults with R/R CD20 LBCL, including diffuse LBCL, high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and grade 3B follicular lymphoma with at least two prior lines of systemic antilymphoma therapy. They were treated with two step-up doses of epcoritamab followed by 48-mg full doses in 28-day cycles, including weekly treatment for cycles 1-3, biweekly treatment for cycles 4-9, and treatment every 4 weeks for cycle 10 and any subsequent cycles, until disease progression or unacceptable toxicity.

In the current subgroup analysis of 96 CAR T–naïve patients, median duration of response was 18.4 months, median duration of complete response was 28.6 months, and an estimated 46% of patients remained in complete response at 36 months, Karimi said.

Median progression-free survival duration was 4.3 months overall and 33.3 months among complete responders. Median overall survival was 15.4 months and was not reached in complete responders.

At 3 years, an estimated 40% of patients overall and 83% of complete responders had not initiated any other antilymphoma therapy, and of the 35 who received subsequent antilymphoma therapy, 10 (29%) received CAR T. Six of the 10 were alive at data cutoff, and 33 of 74 patients evaluable for minimal residual disease (MRD) were MRD-negative.

The most common treatment-emergent adverse events were cytokine release syndrome (CRS) in 60% of patients, diarrhea in 24%, pyrexia in 23%, fatigue in 22%, neutropenia in 22%, and injection-site reaction in 21%. 

Fatal reactions occurred in 18 patients. Of these, nine were related to COVID-19 infection. CRS events were mostly of grade 1 or 2; 4% were of grade 3. CRS occurred most often following cycle 1 and resolved in all but two patients. ICANS occurred in seven patients, clinical tumor lysis syndrome occurred in two patients, and immunoglobulin G levels decreased by a median of about 20% after the story of treatment and remained stable over time, Karimi noted.

“These findings show that epcoritamab can be administered safely and effectively in CAR T–naïve or CAR T–exposed patients with R/R LBCL,” she said.

Karimi reported relationships with AstraZeneca, Lily/Loxo, Merck, AbbVie, ADC Therapeutics, Xencor, and Roche/Genentech. 

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape Medical News, MDedge, and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached atsworcester@mdedge.com or on X@SW_MedReporter.