Outcomes with imetelstat in myelofibrosis: A systematic review and meta-analysis.

Abstract

e18593 Background: Myelofibrosis (MF) patients who progressed on Janus Kinase inhibitors (JAKi), and are ineligible for allogeneic stem cell transplant have poor prognoses and limited treatment options. Imetelstat, a telomerase inhibitor, demonstrated potential benefit in reversing bone marrow fibrosis in MF. This meta-analysis aims to evaluate outcomes of Imetelstat in MF patients. Methods: A comprehensive literature search was conducted on PubMed, Embase, ClinicalTrials.gov, Cochrane, and Google Scholar, adhering to PRISMA guidelines. Three prospective studies reporting outcomes of myelofibrosis (MF) in adult patients treated with Imetelstat were included after screening of 284 articles. The inter-study variance was calculated using the DerSimonian-Laird estimator proportions, and a 95% Confidence Interval (CI) was extracted to compute a pooled analysis using the ‘meta’ package by Schwarzer et al. in the R programming language (version 4.3.0). Results: A total of 197 MF patients were included for analysis. The median age was 67 (31-86) years and 62% were male. 58% had primary MF while 42% had MF secondary to essential thrombocytosis or polycythemia vera. JAK2 mutation was reported in 62% of patients and 9% had calreticulin (CALR) mutation. 37% of patients were treated with at least two prior lines of therapy, 26% were transfusion dependent, and 33% were refractory to JAKi. According to the dynamic international prognostic scoring system, 57% of patients had intermediate-risk disease, while 43% had high-risk disease. Baseline bone marrow (BM) fibrosis was reported in 58% of patients, and 62% had a spleen size greater than 15 cm. ECOG score was 1-2 in 80% of the patients while it was 2-3 in 20%. Imetelstat dosing was 9.7 mg/kg (76%) or 4.7 mg/kg (24%). The duration of Imetelstat treatment, reported by two studies, ranged from 22.3 to 25.1 months. The pooled overall survival (OS) at 1 year, as reported by two studies, was 80.95% (95% CI: 74.95-86.93, p=0.54, I²=0.0%). The median pooled OS ranged from 19.9 to 33.8 months. The pooled spleen volume reduction (SVR) of 10%, 20% and 35% was 22.40 (95% CI 0.0-50.76, p = 0.0001), 11.44 (95% CI 0.00-30.95, p = 0.0006), and 4.42 (95% CI 0.0-14.31, p = 0.0152), respectively, while the pooled reduction of more than one grade in BM fibrosis was reported in 14.79% (95% CI: 4.70-24.88, p=0.04, I²=67.5%) of patients. Most common reported adverse event was anemia (42%) followed by thrombocytopenia (41%), and diarrhea (37%). Conclusions: This meta-analysis shows good efficacy of Imetelstat in MF patients with an acceptable safety profile. However, results should be interpreted cautiously considering the small sample size and large clinical trials are needed to consolidate these findings.