Aaron Gerds,1 Srdan Verstovsek,2 Alessandro Vannucchi,3 Haifa Kathrin Al-Ali,4 David Lavie,5 Andrew Kuykendall,6 Sebastian Grosicki,7 Alessandra Iurlo,8 Yeow Tee Goh,9 Mihaela Lazaroiu,10 Miklos Egyed,11 Maria Laura Fox,12 Donal McLornan,13 Andrew Perkins,14 Sung-Soo Yoon,15 Vikas Gupta,16 Jean-Jacques Kiladjian,17 Rafe Donahue,18 Jun Kawashima,18 Ruben Mesa19
1Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA; 2The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 3University of Florence and AOU Careggi, Florence, Italy; 4University Hospital of Halle, Halle, Germany; 5Hadassah-Hebrew University Medical Center, Jerusalem, Israel; 6Moffitt Cancer Center, Tampa, FL, USA; 7Medical University of Silesia, Katowice, Poland; 8Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; 9Singapore General Hospital, Singapore; 10Policlinica de Diagnostic Rapid Brasov, Brasov, Romania; 11Somogy County Mór Kaposi General Hospital, Kaposvár, Hungary; 12Vall d’Hebron Institute of Oncology, University Hospital Vall d’Hebron, Barcelona, Spain; 13Guy's and St Thomas' NHS Foundation Trust, London, UK; 14Monash University, Melbourne, Australia; 15Seoul National University Hospital, Seoul, South Korea; 16Princess Margaret Cancer Centre, Toronto, Ontario, Canada; 17Université de Paris, AP-HP, Hôpital Saint-Louis, Centre d’Investigations Cliniques, INSERM, CIC1427, Paris, France; 18Sierra Oncology Inc., San Mateo, CA, USA; 19Mays Cancer Center at UT Health San Antonio MD Anderson, San Antonio, TX, USA
Background: MMB, an oral JAK1/2 and ACVR1/ALK2 inhibitor, was evaluated (vs DAN) in a pivotal phase 3 study of MF patients previously treated with a JAK inhibitor (JAKi). This subgroup analysis evaluated MOMENTUM patients with baseline platelet counts ≤150 × 109/L.
Methods: Eligibility: Primary or post-ET/PV MF; DIPSS high risk, Int-2, or Int-1; total symptom score (TSS) ≥10; hemoglobin <10 g/dL; prior JAKi ≥90 days, or ≥28 days if red blood cell transfusions ≥4 units in 8 weeks or grade 3/4 thrombocytopenia, anemia, or hematoma; palpable spleen ≥5 cm; platelets ≥25 × 109/L. JAKi taper/washout ≥21 days. Randomization 2:1 to MMB 200 mg or DAN 600 mg qd (+ placebo) for 24 weeks. Primary end point: TSS response (≥50% reduction from baseline) rate at week 24. Secondary end points at week 24: transfusion independence (TI) rate, splenic response rate (SRR; ≥25% volume reduction from baseline), TSS change from baseline, SRR (≥35% reduction), and rate of zero transfusions since baseline.
Results: Mean baseline TSS: 29 MMB, 26 DAN, hemoglobin: 8.1 g/dL MMB, 7.8 g/dL DAN; and platelets: 74 × 109/L MMB, 73 × 109/L DAN. Efficacy results are consistent with the intention-to-treat analysis set for MMB versus DAN, respectively: TSS response rate (29.6% vs 11.6%), TI rate (32.1% vs 18.6%), SRR ≥25% (39.5% vs 7.0%), TSS change (-10.7 vs -3.8), SRR ≥35% (22.2% vs 4.7%), and rate of zero transfusions (30.9% vs 11.6%). Most common grade ≥3 treatment-emergent adverse events (TEAEs) were thrombocytopenia (MMB, 31%; DAN, 16%) and anemia (MMB, 7%; DAN, 14%); grade ≥3 bleeding events: 9% MMB, 5% DAN. TEAEs leading to study drug discontinuation: 15% MMB, 19% DAN. A trend toward improved overall survival up to week 24 was seen with MMB versus DAN [hazard ratio (95% CI) = 0.490 (0.195-1.235)]. Analyses of patients with baseline platelets <100 × 109/L (n = 100) and baseline platelets <50 x 109/L (n = 31) show similar efficacy, safety, and survival profiles for MMB versus DAN.
Conclusions: In symptomatic, anemic, and thrombocytopenic MF patients, MMB was superior to DAN for symptom responses, transfusion requirements, and spleen responses with comparable safety and favorable survival. MMB may address a critical unmet need in thrombocytopenic MF patients.
Clinical trial identifier: NCT04173494.
