Niktimvo Effective in Recurrent or Refractory GVHD

Graft-versus-host disease (GVHD) occurs when donor immune cells attack the host's organs. GVHD can manifest as acute or chronic, which can last a lifetime.

Image credit: Nadezhda Kozhedub - stock.adobe.com

Patients with recurrent or refractory graft-versus-host disease (GVHD) had a high rate of response to three different doses of intravenous Niktimvo (axatilimab), according to a new study of the efficacy and safety of the drug.

The results of the phase 2 AGAVE-201 trial were published in New England Journal of Medicine and come approximately one month after Niktimvo was approved by the FDA. GVHD occurs when immune cells received from a donor attack the recipient’s organs. Acute GVHD manifests within 100 days of the stem cell transplant, while chronic GVHD usually starts more than 3 months after the transplant and can last a lifetime. The symptoms between acute and chronic GVHD also differ.

“Frontline chronic GVHD therapies fail to induce durable responses in more than half of patients who, despite increased use of new therapies, have disease that subsequently progresses to end-organ impairment,” the authors wrote in the paper. “Treatments that reduce fibrosis and inflammation in patients with recurrent or refractory chronic GVHD are needed.”

AGAVE-201 was a multinational, pivotal, randomized study that evaluated the efficacy and safety of Niktimvo 0.3 mg per kilogram of body weight every two weeks, 1 mg per kilogram every two weeks, or 3 mg per kilogram every four weeks in 241 patients. The patients were assigned in a randomized fashion 1:1:1 to the three dosages.

A total of 239 patients received Niktimvo and at the data cutoff date, 98 (41%) patients were still receiving treatment. Patients had been treated with a median of 4 prior systemic chronic GVHD therapies, the majority (80%) being treated with Imbruvica (ibrutinib), Jakafi (ruxolitinib), Rezurock (belumosudil), or a combination of these therapies. For more than half (55%) of patients, their disease had progressed or had not responded to their previous therapy.

The overall response in the first 6 cycles was:

• 74% (95% CI, 63-83) in the 0.3-mg group
• 67% (95% CI, 55-77) in the 1-mg dose group
• 50% (95% CI, 39-61) in the 3-mg dose group

Response to Niktimvo was fast. Patients in all 3 dosage groups responded with a median time of less than 2 months, and at 12 months, the majority had a durable response (60% for 0.3 mg, 60% for 1 mg, 53% for 3 mg). The median overall survival was not reached in any of the dose groups, while the 12-month survival was 98% for 0.3 mg, 91% for 1 mg and 83% for 3 mg.

In the first six cycles, 60% of patients in the 0.3-mg group, 69% in the 1-mg group and 41% in the 3-mg group, there was a clinically meaningful reduction in chronic GVHD symptoms, as defined as a greater than five-point reduction in the modified Lee Symptom Scale score. More than 90% of patients with chronic GVHD of the skin had sclerotic skin manifestations, and the 0.3-mg group had a 44% reduction, the 1-mg group had the 34% reduction and a 60% of patients in the 3-mg group.

Transient laboratory abnormalities were the most common adverse events and the incidence and grading of these increased as the dosage escalated. In 8% of patients in the 0.3-mg group, 5% in the 1-mg dose group and 1% in the 3-mg dose group there were infusion-related reactions. In addition, infections were common in all 3 groups in 73% for each of the 0.3-mg and 1-mg groups and 70% in the 3-mg group. Half (49%) of the patients on the 0.3-mg dose, 60% on the 1-mg dose, 71% on the 3-mg dose reported grade 3 or higher adverse events.

The key limitation of the study was the lack of a comparator group that was not Niktimvo. Another limitation was that patients had to discontinue most systemic chronic GVHD therapy. The researchers noted that additional studies will evaluate Niktimvo in earlier treatment of GVHD.

“The AGAVE-201 study showed that single-agent therapy with axatilimab is effective for many patients with recurrent or refractory chronic GVHD, including those in whom standard-of-care therapies failed,” the authors concluded.