TRANSFORM-1 Phase 3 study: Efficacy and safety of navitoclax plus ruxolitinib in patients with untreated myelofibrosis
Blood, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Basım Tarihi: 2026
- Doi Numarası: 10.1182/blood.2025032360
- Dergi Adı: Blood
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE
- İstanbul Medipol Üniversitesi Adresli: Evet
Özet
The phase 3 TRANSFORM-1 study evaluated ruxolitinib (RUX) in combination with navitoclax (NAV) or placebo (PBO) in Janus kinase inhibitor–naïve adults with intermediate-2 or high-risk myelofibrosis and Eastern Cooperative Oncology Group performance status of ≤2. Patients were randomized 1:1 to NAV (200 mg/d starting dose, or 100 mg escalated to 200 mg/d) or PBO, with RUX dosed per label. The primary end point was ≥35% spleen volume reduction (SVR) at week 24 (SVR35W24). Secondary end points included change from baseline in total symptom score (TSS) at week 24 and SVR35 at any time. A total of 252 patients (NAV+RUX, n = 125; PBO+RUX, n = 127; median follow-up 20.3 months) were randomized; >80% had intermediate-2 risk, and ∼50% had high-molecular risk disease. SVR35W24 was achieved by 63.2% with NAV+RUX vs 31.5% with PBO+RUX (P <.0001). Mean change in TSS at week 24 was not significantly different between NAV+RUX and PBO+RUX (−10.2 vs −11.6; P =.2852). SVR35 at any time was achieved in 76.8% with NAV+RUX vs 44.1% with PBO+RUX (nominal P <.0001). A ≥20% variant allele frequency reduction (exploratory end point) occurred in 58.5% (95% confidence interval [CI], 49.0-67.5) with NAV+RUX and 45.5% (95% CI, 36.4-54.8) with PBO+RUX. NAV+RUX showed higher hematologic toxicity vs PBO+RUX (grade 3/4 thrombocytopenia, 54.0% vs 19.2%; grade 3/4 neutropenia, 40.3% vs 8.8%); diarrhea (any grade, 41.9% vs 16.8%) was also more common. Cytopenias were generally manageable and reversible with dose adjustments. This trial was registered at www.clinicaltrials.gov as NCT04472598.