Efficacy of Axatilimab in the Management of Chronic Graft-Versus-Host Disease

Chronic graft versus host disease (cGVHD) is a major cause of late non-relapse morbidity and subsequent mortality in patients with allogeneic hematopoietic stem cell transplant (HSCT). Despite various treatment options, therapy failure is common which highlights the necessity for exploration of newer therapies. This systematic review aims to evaluate the efficacy of axatilimab, a monoclonal antibody that inhibits Colony-stimulating factor 1 receptor (CSF-1R), in managing refractory cGVHD.

We conducted a systematic review per PRISMA Statement 2020 guidelines and included 3 studies after searching 5 major databases, PubMed, Cochrane, Medline, Embase, and Clinicaltrials.gov. Inter-study variance was calculated, and a pooled analysis was performed using the ‘meta’ package by Schwarzer et al. in the R programming language (version 4.16-2).

A total of 292 patients from three studies were included in this systematic review and meta-analysis. The included studies were phase I 1(33.33%), phase I/II 1(33.33%) and phase II 1(33.33%). The median age of the patients was 58 years (range: 16-73) and 63% were male (184/292). The median time from cGVHD to the first dose of axatilimab was 3.57 years. The median time to response was 6 weeks (range: 4.5-12). The pooled overall response was 64% (95% CI 0.58-0.69, I²=0%, p=0.86) and the mortality rate was 6% (95% CI 0.04-0.10, I²=0%, p=0.72). One study reported that greater than 50 % of patients maintained a response for greater than 12 months. The gastrointestinal tract exhibited the most favorable response to treatment, whereas the eyes and skin showed modest improvement. The response rate in Esophagus was 74% (95%CI: 0.50-0.89, I²=74%, p=0.02), musculoskeletal was 67% (95% CI: 0.53-0.79, I²=51%, p=0.13) and skin was 26% (95% CI: 0.15-0.40, I²=50%, p=0.14). The pooled incidence of 7-point improvement in LEE score was 49% (95% CI 0.42-0.56, I²=0%, p=0.47) and the incidence of grade 3 or above treatment-related adverse effects was 28% (95% CI 0.17-0.42, I²=61%, p=0.11). AST elevation was the most common adverse effect with a pooled incidence of 35% (95% CI 0.30-0.41, I²=0%, p=0.42) followed by CPK elevation 34% (95% CI 0.29-0.40, I²=0%, p=0.45) and amylase elevation 20% (95% CI, 0.16-0.26, I²=14%, p=0.31). The pooled incidence of drug discontinuation due to treatment-related adverse events was 16% (95% CI: 0.12-0.20, I²=0%, p=0.94).

In this systematic review, axatilimab exhibited promising therapeutic outcomes for refractory cGVHD based on the findings from Phase I and II clinical trials, with an acceptable safety profile. However, prospective clinical trials with randomization are needed to consolidate these findings.

Abhyankar:CSL Behring, Miltenyi Biotec.: Research Funding; Incyte: Consultancy. McGuirk:Envision: Consultancy; Caribou bio: Consultancy; CRISPR therapeutics: Consultancy; NEKTAR therapeutics: Consultancy; Novartis: Consultancy; Autolus: Consultancy; Kite: Consultancy; Allo Vir: Consultancy; Sana technologies: Consultancy; Legend biotech: Consultancy; BMS: Consultancy.