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Emapalumab exhibited excellent tolerability in patients following hematopoietic stem cell transplantation (HSCT) to combat or avert graft failure, according to study results presented at ASH Annual Meeting 2023.
HSCT is susceptible to immune-mediated graft failure, a complication lacking effective interventions. Recognizing various pretransplant risk factors for this issue, recent research identified interferon gamma (IFNγ) as a pivotal and actionable cytokine in the pathophysiology of graft failure. Additionally, CXCL9, an indicator downstream of IFNγ production, is a potential biomarker.
This study was a comprehensive international multicenter retrospective pooled analysis of emapalumab, an IFNγ neutralizing agentcurrently FDA-approved for the treatment of hemophagocytic lymphohistiocytosis, and evaluated its efficacy in preventing or treating immune-mediated graft failure post-HSCT.
The safety and initial efficacy of emapalumab were evaluated in a predominantly pediatric patient cohort using 2 distinct approaches: treatment for graft failure and prophylactic measures against graft failure.
A total of 36 patients received emapalumab for graft failure treatment or prophylaxis. Of these, 25 patients received it for graft failure following HSCT. Most (16) of these cases were from bone marrow failure syndromes.
In centers in the US, patients received emapalumab as treatment if they displayed clinical and laboratory signs of graft failure following HSCT. Treatment criteria included meeting at least 2 of the following: having an HLA-mismatched donor or prior graft failure, unexplained fever above specific temperature thresholds, decline in absolute neutrophil count postengraftment, delayed neutrophil engraftment, and elevated real-time CXCL9 levels.
Meanwhile, patients at European centers received prophylactic emapalumab to preempt graft failure if deemed at high risk before transplantation. High-risk status was determined by a prior history of graft failure after HSCT or meeting 2 or more established risk factors: experiencing diseases associated with a high risk of graft failure such as severe aplastic anemia, thalassemia, or primary hemophagocytic lymphohistiocytosis (HLH); receiving an ex-vivo T cell-depleted stem cell product; and undergoing transplantation from an unrelated cord blood unit or a mismatched related/unrelated donor.
All patients administered emapalumab experienced no complications or side effects attributable to therapy, and no infections were linked to emapalumab. Among the patients treated with emapalumab for impending graft failure, 56% (14 of 25) successfully engrafted and resolved concerns related to graft failure; the remaining 44% experienced graft failure.
Responders showed a median absolute neutrophil count of 0.29×103 cells/μL (range, 0.05 to 0.79) before emapalumab, which rose to a median of 0.6×103 cells/μL (range, 0 to 5.1) on day 3 and 2.97×103 cells/μL (range, 0.85 to 8.7) on day 7 following emapalumab administration.
In the treatment group, 80% (20 of 25) of patients had elevated CXCL9 levels before administration of emapalumab. The median pre-emapalumab CXCL9 level was elevated to 2.4 times the upper limit of normal (ULN; range, 0.3 to 157.8). The median pre-emapalumab CXCL9 level among patients who experienced graft failure was 3.3 times ULN (range, 0.7 to 157.8) compared with a median of 2.2 times ULN (range, 0.3 to 30.4) in those who displayed signs of graft failure but did not experience graft failure (P =.24).
A total of 11 patients received prophylactic emapalumab based on prior graft failure history or pretransplant risk factors. Emapalumab was well-tolerated in these patients, with 91% (10 of 11) successfully engrafting. However, one patient with a history of graft failure experienced recurrent graft failure, displaying a pre-HSCT (day −2) CXCL9 level 4 times the ULN.
Although the conclusions regarding efficacy are provisional due to the study’s constraints, the investigation successfully identified a subset of patients facing a notably high graft failure rate (44%). Preliminary data indicated that emapalumab might prevent graft failure in patients displaying early signs of impending failure at the time of treatment. These initial safety and efficacy findings support further exploration through an expansive prospective study on IFNγ blockade for preventing graft failure subsequent to HSCT.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Sabulski A, Jodele S, Cook E, et al. Emapalumab for treatment of impending graft failure. Presented at ASH Annual Meeting 2023. December 9-12, 2023. San Diego, CA. Abstract 114.
