番茄社区app

HOUSTON -- More than 60% of patients with relapsed/refractory large B-cell lymphoma (LBCL) had objective responses to the bispecific antibody epcoritamab (Epkinly), according to updated results from a pivotal trial.

Overall, 63% of 157 patients responded, including 39% who had complete responses. Responses by lymphoma subtype consisted of 61% of patients with diffuse (D) LBCL and high-grade B-cell lymphoma that made up most of the population, all four patients with primary mediastinal B-cell lymphoma, and all five with follicular lymphoma. Median duration of response (DOR) was 15.5 months, including 20.8 months in patients with complete response.

For treatment-emergent adverse events, half of the patients had cytokine release syndrome (CRS, any grade) and 20% to 25% had neutropenia, pyrexia, fatigue, nausea, and diarrhea, reported Yasmin Karimi, MD, of the University of Michigan Comprehensive Cancer Center in Ann Arbor, during the Society of Hematologic Oncology meeting.

"Progression-free survival was not reached, and an estimated 87% of patients remained progression-free at 12 months," said Karimi. "Longer follow-up reaffirms deep and durable complete responses, which translates into favorable long-term outcomes, with median overall survival not reached in complete responders. Safety was manageable and consistent with previous reports, with no new safety signals."

The data came from the phase I/II EPCORE NHL-1 trial, which supported the recent FDA accelerated approval of epcoritamab.

The bispecific antibody targets CD3 and CD20, and primary results from EPCORE NHL-1 showed a 63% overall response rate. The trial included adults with DLBCL not otherwise specified, including DLBCL arising from indolent lymphoma and high-grade B-cell lymphoma, that had failed to respond or progressed on two or more prior systemic therapies. Patients with DLBCL and high-grade B-cell lymphoma accounted for 148 of the 157 patients enrolled in the trial.

The patient population had received a median of three prior systemic therapies, and 70% had received more than three. About 60% of the patients had primary refractory disease, 82% were refractory to the most recent therapy, and 75% were refractory to two or more consecutive lines of therapy.

"Nearly 40% of the patients had received prior CAR T-cell therapy, and three quarters of these patients were refractory to CAR-T," said Karimi.

Adverse events included two deaths that were considered treatment related, one from COVID-associated pneumonia and one from ocular cancer involving a patient with multiple confounding factors, she said. Though half the patients developed CRS, most cases were low grade. All but one case of CRS resolved without incident within a median of 2 days.

The updated results showed the response rate and duration of response remained the same as at the time of FDA accelerated approval. Median duration of response had yet to be reached in patients with LBCL and prior CAR T-cell therapy. Median overall survival was 18.5 months in the overall population and in the DLBCL/high-grade B-cell lymphoma subgroup.

Following the presentation, co-moderator Christopher Flowers, MD, of the University of Texas MD Anderson Cancer Center in Houston, asked how the toxicity with epcoritamab compared with toxicities of other therapies used in late-line treatment of LBCL.

Karimi said toxicity should be considered within the context of sequencing available therapies.

"There's a lot of logistics related to it," she said. "We want patients to be close enough to a center that has access to tocilizumab or has knowledge of CRS protocols. Neurotoxicity occurs with [bispecific antibodies] but is less common than with CAR-T. Cytopenias, particularly neutropenia, are easily managed with [growth factor] and transfusion support.

"In terms of sequencing, a lot of it comes down to individualizing treatment decisions between patients and providers, including side effect profile. For a lot of our patients, these are palliative-intent therapies, doing whatever we can to maximize quality of life and making sure that the treatment fits what they want for their goals."

Co-moderator Laurie Sehn, MD, of BC Cancer and the University of British Columbia in Vancouver, asked how clinicians might choose between limited-duration treatment with glofitamab (Columvi), the other bispecific antibody approved for relapsed/refractory LBCL, and indefinite treatment with epcoritamab.

"At what point do you rethink the indefinite strategy and maybe stop treatment in an individual patient?" Sehn asked.

Karimi said some patients push back against stopping treatment when it is working but acknowledged that taking a drug holiday might warrant consideration for selected patients.

"I think we're going to learn in real-world practice whether or not we can really stop early," she said.

This story has been updated with the correct spelling of the presenter's name.

Comment