Amongst sufferers experiencing persistent graft-versus-host illness (cGVHD), the transition of remedy with Niktimvo (axatilimab) to a dose of 0.6 milligrams per kilogram (mg/kg) each 4 weeks appeared possible amongst these handled with a dose of 0.3 mg/kg each two weeks, based on knowledge from the pivotal part 2 AGAVE-201 trial.
“General, these findings assist the security and feasibility of [Niktimvo] at a dose of 0.6 mg/kg month-to-month,” Dr. Nosha Farhadfar of Methodist Physicians Texas Transplant Specialists – Grownup Blood Marrow Transplant, San Antonio in Texas, stated throughout a presentation of the info on the 2025 ASH Annual Assembly. “Future analyses are deliberate to additional consider the efficacy and security at this dosing. Additionally, I feel we’d like real-world proof, which is important to enhance this discovering and supply a broader assist for the therapeutic method.”
Glossary
Graft-Versus-Host Illness (GVHD): A attainable complication after an allogeneic stem cell transplant. It occurs when the donor’s immune cells see the affected person’s physique as overseas and start to assault it. Signs can vary from pores and skin rashes to abdomen or liver issues.
Creatine Phosphokinase (CPK) Enhance: An increase within the degree of an enzyme present in muscle tissue. Larger ranges in blood checks can imply the muscle tissue are irritated, infected, or injured.
Oropharyngeal Ache: Ache at the back of the mouth or throat. It may possibly occur because of infections, irritation from remedies, or mouth sores.
Pruritus: A medical phrase for itching. It may be gentle or intense and could also be brought on by remedy, dry pores and skin, or sure medical circumstances.
Pyrexia: The medical time period for fever — when physique temperature is larger than regular. Fever could be a signal of an infection or irritation and ought to be reported to a healthcare staff.
AGAVE-201 Trial Design
Within the AGAVE-201 trial, sufferers who met pre-specified standards might change their dosing schedule from 0.3 mg/kg each two weeks to 0.6 mg/kg each 4 weeks, with out dose capping. Investigators evaluated the security and feasibility of transitioning from the accepted dose utilizing long-term knowledge from the trial.
Among the many 19 sufferers who transitioned to the 0.6-mg/kg dose, the median age was 50 years, with the bulk being male (63.2%). Median time from analysis to randomization was 4.39 months and the median variety of organs concerned was three. Nearly all of sufferers reported with extreme illness (73.7%), and had beforehand obtained an FDA-approved agent (89.5%).
“The subgroup that transitioned to month-to-month dosing was usually corresponding to the general [population who received the 0.3 mg/kg dose every two weeks,]” Farhadfar stated.
Therapy with a dose of 0.6 mg/kg each 4 weeks led to an general response fee of 94.7%, together with partial and full response charges of 89.5% and 5.3%, respectively.
“One affected person with steady illness was transitioned to multi-dosing on the investigator’s discretion,” Farhadfar added.
Toxicities After Switching Doses
After switching doses, sufferers had been on remedy for a median of 20.9 months. At knowledge cutoff, 16 sufferers (84.2%) maintained the 0.6 mg/kg dose. Of the three who didn’t, two sufferers switched again to the FDA-approved dose at 4.6 and 18.6 months following the swap, respectively, whereas one affected person switched again because of an facet impact at 3.4 months. Within the general inhabitants, the remedy period was 7.4 months.
Farhadfar famous that the incidence of grade 3 (extreme)or larger unintended effects was larger with the month-to-month dose in contrast with the FDA-approved dose (52.6% versus 36.8%, respectively), which was to be anticipated given the longer remedy period seen.
“Nevertheless, once you have a look at the incidence of treatment-related opposed occasion, that is comparable earlier than and after the month-to-month dosing, suggesting that the rise in opposed occasion could also be extra reflective of longer remedy publicity slightly than the direct impact of a brand new dosing schedule.”
After the swap, there was additionally a better incidence of significant unintended effects (42.1% versus 5.3%, respectively); nonetheless, much less sufferers had dose interruptions (21.1% versus 36.8%). Investigators noticed a slight improve within the quantity of dose reductions (three versus none, respectively) and discontinuations (three versus none).
The most typical unintended effects included fatigue (26.3%), higher respiratory tract an infection (26.3%), headache (21.1%), stomach ache (15.8%), cough (15.8%), creatine phosphokinase improve (15.8%), diarrhea (15.8%), falls (15.8%), oropharyngeal ache (15.8%), pruritis (15.8%) and pyrexia (15.8%).
In August 2024, the FDA accepted Niktimvo 0.3 kg/mg each two weeks for the remedy of cGVHD in sufferers who beforehand obtained two or extra traces of remedy, primarily based on outcomes from the AGAVE-201 trial. Farhadfar emphasised that the 0.6-mg/kg dose is an investigational schedule change.
“So we have to interpret the outcomes [cautiously], because the out there efficacy knowledge for the month-to-month dosing are restricted and the pattern dimension may be very small,” she added. “My private choice is to maintain the affected person on the every-two-weeks dosing, and contemplate transitioning to month-to-month dosing solely in a state of affairs the place the sufferers are unable, unwilling or there are some challenges that make this every-two-weeks dosing impractical.”
Reference
“Security and feasibility of 0.6 mg/kg each 4 weeks dosing of axatilimab in sufferers handled within the AGAVE-201 research,” by Dr. Nosha Farhadfar et al., Blood.
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