Immunotherapy combination shows ‘remarkable’ activity for patients with advanced lymphoma
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Natural killer cells combined with a bispecific antibody induced response among nearly 90% of patients with relapsed or refractory CD30-positive lymphoma, according to phase 1/phase 2 trial results.
All patients who received the recommended phase 2 dose of the investigational therapy achieved objective response, findings presented at American Association for Cancer Research Annual Meeting showed.
Background
Patients with CD30-positive lymphomas who do not respond to standard therapies eventually will experience disease progression as their tumors become resistant to treatment, according to Yago L. Nieto, MD, PhD, professor in the department of stem cell transplantation and cellular therapy at The University of Texas MD Anderson Cancer Center.
Nieto said the trial’s approach was based on extensive preclinical work in the lab of his colleague, Katy Rezvani, MD, PhD, director of translational research in the department of stem cell transplantation and cellular therapy at MD Anderson. Rezvani’s lab found that natural killer (NK) cells preactivated with cytokines, expanded and precomplexed with AFM13 (Affimed) — a bispecific antibody — induced much greater responses on mouse models than either preactivated NK cells or AFM13 alone.
“We hypothesized that combining a bispecific molecule with cord blood-derived NK cells would induce [chimeric antigen receptor]-like NK cells that are more active than conventional NK cells and persist within the body for a longer amount of time,” Nieto told Healio.
Study participants “were in dire straits” and had experienced disease progression despite having received standard therapies, Nieto said.
Methodology
The single-center study included 22 patients (mean age, 40 years; range, 20-70; 68% male) with relapsed or refractory CD30-postive lymphomas who had received a median seven prior lines of therapy (range, 1-14).
All study participants had experienced disease progression despite use of brentuximab vedotin (Adcetris, Seagen), and all but one patient previously received an immune checkpoint inhibitor.
Study participants received lymphodepleting chemotherapy, followed by two cycles of AFM13-NK cell infusions a median of 56 days apart, in addition to weekly doses of AFM13 after the cellular therapy infusions.
AFM13 is a bispecific antibody that binds to CD16A on the surface of NK cells and CD30, an antigen present in all Hodgkin lymphoma cells and a sizable proportion of T-cell lymphomas, Nieto said.
The AFM13 molecule is bound to donor-derived NK cells at MD Anderson’s good manufacturing practice facility in an incubation process called “precomplexing.” This causes the final cell therapy product to “act like a magnet” that identifies and binds to CD30-positive lymphoma cells, Nieto said.
Median follow up was 9 months (range, 1-19).
Key findings
Investigators did not observe any dose-limiting toxicities during study and established the recommended phase 2 study dose at 108 NK cells/kg.
Safety results showed no cases of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome or graft-versus-host disease.
Seventeen of 19 patients achieved a metabolic response to therapy, equating to an overall response rate of 89.5%. This included 10 patients with complete response and seven patients with partial response.
All 13 patients who received the recommended phase 2 dose had a metabolic response to therapy, including eight with complete responses and five with partial responses.
“All patients who received the recommended phase 2 dose responded to therapy, with nearly two-thirds of them achieving a complete response,” Nieto said. “That level of activity is remarkable in this patient population.”
Six of the patients who received the recommended phase 2 dose had ongoing responses at the time of data cutoff, including two patients with ongoing responses 10 months after infusion.
At 9 months, investigators noted an EFS rate of 52% and OS rate of 81% across all dose levels.
Clinical implications
The results thus far have exceeded initial expectations for the therapy, Nieto said.
“We were very surprised by the depth of the responses,” he told Healio.
“The first few patients we treated were extremely debilitated by the effects of their tumors and have progressed despite a number of previous treatments,” he added. “They all had an initial complete response to therapy with minimal side effects.”
The researchers plan to pursue additional study by giving patients four cycles of therapy instead of two “to explore the curative potential of this treatment,” Nieto said.
Perspective
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Henry Chi Hang Fung, MD, FACP, FRCPE
This could potentially be a breakthrough treatment for patients with relapsed or refractory CD30-positive lymphomas. Treatment options are very limited for this group of patients — specifically those who experience disease progression after hematopoietic stem cell transplant and brentuximab vedotin. An 89% ORR with a 52% complete response at median follow-up of 9 months is very impressive, in addition to the PFS and OS results.
Collapse
Nieto YL, et al. Abstract CT003. Presented at: American Association for Cancer Research Annual Meeting; April 8-13, 2022; New Orleans.
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