A combination of acimtamig,a bispecific innate cell engager (ICE),and AlloNK,an off-the-shelf natural killer cell product,is showing positive results in treating relapsed or refractory (R/R) classical Hodgkin lymphoma. The treatment offers a new option for patients with otherwise poor prognoses.

dr. Joseph Maakaron, of the University of Minnesota, presented the findings at the American Society of Clinical Oncology (ASCO) 2025 annual meeting.”acimtamig in combination with AlloNK shows promising efficacy with a well-managed safety profile with the potential to address an unmet need in patients with R/R Hodgkin lymphoma who have fatigued standard-of-care treatment options,” said Dr. Maakaron.

Classical Hodgkin lymphoma patients who relapse after standard treatments, including chemotherapy, brentuximab vedotin, and checkpoint inhibitors, face a lack of effective options.

A previous monotherapy trial of acimtamig showed some efficacy,and this was further enhanced when combined with AlloNK in a proof-of-concept study.

To further investigate, Dr. Maakaron and his team conducted the phase 2 luminice-203 trial, enrolling 24 patients with R/R Hodgkin lymphoma.

The study involved four cohorts, testing two doses of acimtamig (200 mg or 300 mg weekly for 6 weeks) with two dose levels of allonk, following lymphodepletion for up to three cycles.The trial also included a randomized phase using the Simon two-stage design.

The patients’ median age was 42.5 years (range 23-80), and 67% were men. The majority (66.7%) had extranodal disease and had been heavily pre-treated with brentuximab vedotin and programmed cell death protein 1 inhibitors. They had received a median of 4.5 prior lines of treatment; 58% had undergone previous stem cell transplant and CAR T cell therapy.

“The patients had essentially exhausted all standard-of-care therapy options,” Dr.Maakaron noted.

The study met its primary endpoint, demonstrating an objective response rate of 88%, with 58% achieving complete responses.

Clinically meaningful deep responses were observed across all dose cohorts,with 10 ongoing responses. The progression-free survival estimate at 6 months was 61%.

Maximum peaks were more robust after the third infusion, likely due to achieving a steady state.

The safety profile was consistent with prior reports, with the combination therapy being well-tolerated. The most common side effects were mild to moderate infusion-related reactions, occurring in 50% of patients.

There were no cases of graft vs host disease or immune effector cell-associated neurotoxicity syndrome. cytokine release syndrome (CRS) was reported in six patients shortly after infusion.

All treatment-emergent adverse events, including infusion-related reactions and CRS, were managed with standard interventions and resolved quickly.

There were no fatal treatment-emergent adverse events.

“Acimtamig with AlloNK may provide a safe, effective, and durable new therapeutic option for patients with R/R Hodgkin lymphoma, with a progression-free survival estimate of 61% at 6 months,” Dr. Maakaron stated.

“These early results support the co-administration approach of acimtamig with an off-the-shelf, commercially scalable, allogenic, cryopreserved natural killer cell product in a multicenter setting,” he added.

Expert Highlights Unmet Need

Dr.Sarah C. Rutherford, of Weill Cornell Medicine, commented on the findings, emphasizing the pressing need for better treatments for relapsed patients.

“This is really an unmet need in the field,” she said.

“Novel treatments in R/R classic Hodgkin lymphoma after brentuximab vedotin, checkpoint inhibitors, and autologous transplant are limited, and most don’t really work that well.”

“We tend to use single-agent chemotherapies,repeat checkpoint inhibitors,and radiation,but these patients really suffer because of that,and clinical trial options have been lacking.”

Dr. Rutherford highlighted the importance of safety and tolerability with this new combination.

“I was really struck by the tolerability of this regimen, with only five patients having grade 3 and one [having] grade 4 treatment-emergent adverse events.”

Furthermore, she noted the notable response rates.

“These are the best response rates observed to date in the post-brentuximab vedotin and checkpoint inhibitor setting,and the toxicities appear manageable,” Dr. Rutherford said.

“I think it’s going to be unlikely to be as widely adopted as checkpoint inhibitors as of the nature of the cellular therapy approach, but I do think this is a very promising agent,” Dr.Rutherford said.

“I think it’s the current best available trial option, and in the future, some version of this could become a third-line therapy in this disease.”

“These are the best response rates observed to date…and the toxicities appear manageable.”