FDA Approves Axatilimab-csfr for cGVHD

The FDA has approved axatilimab-csfr (Niktimvo, Incyte Corporation) for the treatment of chronic graft-versus-host disease (cGVHD) in adult and pediatric patients who need additional treatment after at least 2 prior lines of systemic therapy.¹ Axatilimab-csfr, which is a high-affinity antibody, targets the colony stimulating factor 1 receptor, the signaling of which has been demonstrated to be the critical regulatory pathway in the expansion and infiltration of donor-derived macrophages, which mediate the disease processes involved in cGVHD.¹

Axatilimab-csfr was evaluated in the randomized, open-label, multicenter AGAVE-201 trial (NCT04710576).^1,2 During the trial, investigators assessed 3 dosages of axatilimab-csfr in adult and pediatric patients with recurrent or refractory cGVHD who weigh at least 40 kg and have failed at least 2 prior lines of systemic therapy.^1,2 In the first cohort, participants received axatilimab 0.3 milligrams (mg)/kilogram (kg) intravenously (IV) every 2 weeks for up to 2 years; in the second cohort, participants received axatilimab 1 mg/kg IV every 2 weeks for up to 2 years; and in the third cohort, participants received axatilimab 3 mg/kg IV every 4 weeks for up to 2 years.²

For the primary outcome of the trial, investigators looked to measure the overall response rate (ORR) in the first 6 cycles, which was assessed by the number of participants with objective response by cycle 7 (28-day cycles), day 1 and up to day 169. Additionally, investigators defined the responses based on the 2014 National Institutes of Health (NIH) consensus criteria.²

Secondary measures during the trial were the number of participants with a clinically significant improvement in normalized score on the modified 7-day Lee cGVHD Symptom Scale, duration of response (DOR), sustained response rate, organ-specific response rate, joints and fascia response rate (based on refined NIH response algorithm for cGVHD), percent reductions in average daily doses (or equivalent) of corticosteroid, number of participants who discontinued corticosteroid use, percent reductions in average daily doses (or equivalent) of calcineurin inhibitors (CNI), and number of participants who discontinued CNIs, as well as several other measures. For all secondary measures, results were assessed within a timeframe of approximately 30 months.²

The results of the trial showed that ORR was 75% (95% CI: 64, 84) in the 79 patients treated with the recommended dosage of 0.3 mg/kg (up to a maximum dose of 35 mg) as an IV infusion over 30 minutes every 2 weeks until disease progression or unacceptable toxicity. The median time to first response was 1.5 months (range: 0.9 to 5.1), with a median DOR of 1.9 months (95% CI: 1.6, 3.5). In patients who achieved response during the trial, investigators noted that there were no deaths or new systemic therapy initiation in 60% (95% CI: 43, 74) of patients for at least 12 months following response to therapy.¹

“The highest ORR and the least toxicity was observed with the lowest dose,” said Daniel Wolff, MD, chair of the GVHD Center of the University Hospital in Regensburg, Germany, in an interview with ASH Clinical News. “That underlines the crucial importance of sufficiently powered studies in this vulnerable patient group.”³

The most common (≥ 15%) adverse effects (AEs) patients experience during the trial were increased aspartate aminotransferase, infection (pathogen unspecified), increased alanine aminotransferase, decreased phosphate, decreased hemoglobin, viral infection, increased gamma glutamyl transferase, musculoskeletal pain, increased lipase, fatigue, increased amylase, increased calcium, increased creatine phosphokinase, increased alkaline phosphatase, nausea, headache, diarrhea, cough, bacterial infection, pyrexia, and dyspnea.¹

Data from the AGAVE-201 trial were also presented at the American Society of Hematology (ASH) Annual Meeting and Exposition in December 2023. At ASH, presenters showed that the median failure-free survival with axatilimab-csfr was 17.3 months, with 55% of patients reporting clinically meaningful symptom burden reduction. Additionally, complete responses were observed across all organ types.⁴

The Role of the Pharmacist in cGVHD

In a Pharmacy Times Clinical Forum, a panel discussed the integration of pharmacists into care for patients with cGVHD, noting that pharmacist involvement has been shown to improve the quality of life for patients and decrease the financial and medication burdens of the disease.⁵ In a separate Pharmacy Times Clinical Forum, Gabriel Hinojosa, PharmD, BCOP, clinical pharmacy specialist, division of hematology and oncology, UT Southwestern Medical Center, explained further that the role of the pharmacist can also become quite complex, as each patient with cGVHD is affected by the disease differently, meaning their case will also need to be managed by the pharmacist in a personalized fashion.⁶

"cGVHD may impact nearly every organ system of the body, and it affects every patient a little bit differently," Hinojosa said during the Clinical Forum. "No two patients will be the same, and the pharmacist really plays a crucial role both in the initial treatment selection and tailoring that to that specific patient, as well as all the additional supportive care aspects that come along with that."⁶

For cGVHD, Hinojosa explained that pharmacists often use many topical therapies for more mild cases, such as skin creams, eye drops, mouth rinses, and inhaled medications. In each of these categories, the pharmacist helps to select the most effective treatment agent for the patient depending on what type of symptoms or organ involvement they have.⁶

"We also play a large role in helping with the initial dosing of systemic steroids," Hinojosa said. "Then, of course, we assess if and when a patient needs to be transitioned to a different systemic therapy, either to minimize steroid use or [appropriately manage treatment for] a patient who has not responded adequately to steroids. But I will say, one of the largest roles that the transplant pharmacist plays in all this is ensuring that we provide the appropriate supportive care to these patients."⁶

Overall, the role of pharmacists in the education of physicians and other health care professionals about treatments, AE management, and treatment-related supportive care for patients is crucial, according to Krystal Preston, PharmD, BCPS, a senior clinical oncology pharmacist at CVS Health and a clinical pharmacist at the University of Chicago Medicine, during a Clinical Forum.⁵ Because physicians may not be as familiar with the nuances of a treatment as a pharmacist, they can often also be the primary educator for patients around treatment and treatment expectations, as well as potential adverse effects they may experience.⁵

“Patients are not going [to get that information] from the [physician]; they’re going to get that information from us," Preston said. "We have to come up with creative ways to make sure it’s ingrained that [adherence to their medication] is important.”⁵

Editor's Note: This article was updated at 4:32 PM ET on August 14, 2024.

REFERENCES

1. FDA approves axatilimab-csfr for chronic graft-versus-host disease. FDA. August 14, 2024. Accessed August 14, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-axatilimab-csfr-chronic-graft-versus-host-disease
2. A Study of Axatilimab at 3 Different Doses in Participants With Chronic Graft Versus Host Disease (cGVHD) (AGAVE-201). National Library of Medicine. Updated June 14, 2024. Accessed August 14, 2024. https://www.clinicaltrials.gov/study/NCT04710576
3. Hickman RJ. Axatilimab, First-in-Class Treatment for Chronic GVHD, Shows Strong Phase II Results. ASH Clinical News. January 2024. Accessed August 14, 2024. https://ashpublications.org/ashclinicalnews/news/7549/Axatilimab-First-in-Class-Treatment-for-Chronic
4. Braun D. From Axatilimab to Zanubrutinib: Treatment Updates Abound. Pharmacy Practice in Focus: Oncology. 2024;6(1). Accessed August 14, 2024. https://www.pharmacytimes.com/view/from-axatilimab-to-zanubrutinib-treatment-updates-abound
5. Gallagher A. With High Medication Burden of GVHD, Pharmacists Play a Critical Role in Supporting Education, Medication Adherence. Pharmacy Times. Accessed August 14, 2024. https://www.pharmacytimes.com/view/with-high-medication-burden-of-gvhd-pharmacists-play-a-critical-role-in-supporting-education-medication-adherence
6. Guiding Principles in the Management of cGVHD. Pharmacy Times. Accessed August 14, 2024. https://www.pharmacytimes.com/view/guiding-principles-in-the-management-of-cgvhd