TY - JOUR
T1 - MPN-483 Thrombocytopenic Myelofibrosis (MF) Patients Previously Treated With a JAK Inhibitor in a Phase 3 Randomized Study of Momelotinib (MMB) versus Danazol (DAN) [MOMENTUM]
AU - Gerds, Aaron
AU - Verstovsek, Srdan
AU - Vannucchi, Alessandro
AU - Al-Ali, Haifa Kathrin
AU - Lavie, David
AU - Kuykendall, Andrew
AU - Grosicki, Sebastian
AU - Iurlo, Alessandra
AU - Goh, Yeow Tee
AU - Lazaroiu, Mihaela
AU - Egyed, Miklos
AU - Fox, Maria Laura
AU - McLornan, Donal
AU - Perkins, Andrew
AU - Yoon, Sung Soo
AU - Gupta, Vikas
AU - Kiladjian, Jean Jacques
AU - Donahue, Rafe
AU - Kawashima, Jun
AU - Mesa, Ruben
N1 - Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/10
Y1 - 2022/10
N2 - 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 RBC 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 endpoint: TSS response (≥50% reduction from baseline) rate at week 24. Secondary endpoints 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 MMB, 7.8 DAN g/dL, and platelets: 74 × 109/L MMB, 73 × 109/L DAN. Efficacy results are consistent with the ITT analysis set for MMB vs 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 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 vs DAN [HR (95% CI)=0.490 (0.195, 1.235)]. Analyses of patients with baseline platelets <100 × 109/L (N=100) and baseline platelets <50 × 109/L (N=31) show similar efficacy, safety, and survival profiles for MMB vs 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. NCT04173494.
AB - 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 RBC 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 endpoint: TSS response (≥50% reduction from baseline) rate at week 24. Secondary endpoints 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 MMB, 7.8 DAN g/dL, and platelets: 74 × 109/L MMB, 73 × 109/L DAN. Efficacy results are consistent with the ITT analysis set for MMB vs 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 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 vs DAN [HR (95% CI)=0.490 (0.195, 1.235)]. Analyses of patients with baseline platelets <100 × 109/L (N=100) and baseline platelets <50 × 109/L (N=31) show similar efficacy, safety, and survival profiles for MMB vs 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. NCT04173494.
KW - JAK inhibitor
KW - MPN
KW - Phase III
KW - anemia
KW - momelotinib
KW - myelofibrosis
KW - thrombocytopenia
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U2 - 10.1016/S2152-2650(22)01464-1
DO - 10.1016/S2152-2650(22)01464-1
M3 - Article
C2 - 36164014
AN - SCOPUS:85138143484
SN - 2152-2669
VL - 22
SP - S340
JO - Clinical Lymphoma
JF - Clinical Lymphoma
ER -