From April 24, 2020, to December 3, 2021 (data cut-off date), 10 sites in Asia participated in the MOMENTUM trial [20]; 17 Asian patients with MF were enrolled (from Korea, n = 11 [64.7%]; Singapore, n = 4 [23.5%]; Taiwan, n = 2 [11.8%]) (Fig. 1), of whom 11 and 6 were randomly assigned to the momelotinib and danazol group, respectively, and 10 and 3 completed the 24-week randomized phase of treatment. Reasons for treatment discontinuation were AEs (0 in the momelotinib group, 2 [33.3%] in the danazol group) and subject decision (1 [9.1%] in the momelotinib group and 1 [16.7%] in the danazol group). Of the momelotinib and danazol groups, 10 and 3 patients, respectively, continued to the open-label phase and received open-label momelotinib. Eight (72.7%) patients in the momelotinib group and 1 (16.7%) patient in the danazol group completed 24 weeks of the open-label phase.

DAN, danazol; MMB, momelotinib; OL, open-label

Patient baseline and clinical characteristics are summarized in Table 1. Six (54.5%) patients were female in the momelotinib group; no patients were female in the danazol group. At baseline, 54.5% (6/11) and 50.0% (3/6) of patients in the momelotinib and danazol groups, respectively, were diagnosed with primary MF; median platelet counts were 87.0 × 109/L and 89.5 × 109/L, and mean hemoglobin levels were 7.9 g/dL and 7.5 g/dL. All 17 patients received prior ruxolitinib treatment for a mean (SD) duration of 134.4 (116.5) and 64.3 (67.0) weeks in the momelotinib and danazol groups, respectively; one patient in the momelotinib group also received prior fedratinib for 92.4 weeks. At baseline, 18.2% (2/11) and 9.1% (1/11) of patients in the momelotinib group were TD and TI, respectively, versus 50.0% (3/6) and 0% in the danazol group. There were small differences between the treatment groups in sex, age group, MF type, prognostic risk category, spleen volume, and RBC units transfused, but the number of patients was limited and there were no differences in other categories.

TSS response rate was 36.4% (4/11) and 0% (0/6) in the momelotinib and danazol groups, respectively (greater proportion difference, 33.3%; 95% CI, −20.0, 86.68) (Table 2, Figs. 2a, 3).

DAN, danazol; MMB, momelotinib

Percent change in (a) total symptom scores and (b) splenic volume at Week 24 post-dose for individual patients

Analysis includes patients with both baseline and Week 24 data available. DAN, danazol; MFSAF, Myelofibrosis Symptom Assessment Form; MMB, momelotinib

Median MFSAF symptom-scores at baseline and Week 24

At Week 24, the TI rate was 63.6% (7/11; 95% CI, 30.79, 89.07) and 0% (0/6; 95% CI, 0.00, 45.93) in the momelotinib and danazol groups, respectively. SRR (≥ 25% reduction) was 63.6% (7/11; 95% CI, 30.79, 89.07) and 16.7% (1/6; 95% CI, 0.42, 64.12) in the momelotinib and danazol group, respectively; SRR (≥ 35% reduction) was 36.4% (4/11; 95% CI, 10.93, 69.21) in the momelotinib group and 0% (0/6; 95% CI, 0.00, 45.93) in the danazol group (Table 2, Fig. 2b).

At Week 24, the least squares (LS) mean (standard error [SE]) change in TSS from baseline was − 9.52 (2.78) and − 9.19 (4.08) in the momelotinib and danazol groups, respectively (difference, − 0.34; 95% CI, − 10.92, 10.25). Although the difference in LS means was small, the decrease in individual item scores was greater in the momelotinib group than in the danazol group (Table 2, Fig. 3).

At Week 24, the proportion of patients who had zero RBC transfusions was 72.7% (8/11; 95% CI, 39.03, 93.98) and 0.0% (0/6; 95% CI, 0.00, 45.93) in the momelotinib and danazol groups, respectively (Table 2). In the momelotinib group, 18.2% (2/11) of patients were TD and 9.1% (1/11) of patients were TI at baseline; 72.7% (8/11) of patients were transfusion requiring (TR [not meeting the definition of TI or TD]). At Week 24, 0.0% (0/11), 63.6% (7/11), and 36.4% (4/11) of patients were TD, TI, and TR, respectively. In the danazol group, 50.0% (3/6), 0.0% (0/6), and 50.0% (3/6) of patients were TD, TI, and TR at baseline, respectively; there was no change in transfusion status at Week 24. In the momelotinib group, none of the patients with TD at baseline (18.2% [2/11]) achieved TI at Week 24, but both became TR at Week 24; of the eight patients who were TR at baseline, six converted to TI and two remained TR. The patient in the momelotinib arm who was TI at baseline remained TI at Week 24 (100% [1/1]; 95% CI 2.50, 100.00).

Ten and three patients continued or crossed over to open-label momelotinib after the randomized-treatment period, with a median follow-up of 49.6 weeks and 37.4 weeks in the momelotinib and danazol groups, respectively. Fatal events were reported in 9.1% (1/11) of patients in the momelotinib group and 16.7% (1/6) patients in the danazol group, both due to leukemic transformation; median OS and LFS were not reached in either group (Supplementary Fig. S1).

At Week 4, mean hemoglobin levels increased to 9.1 g/dL from the baseline level of 7.9 g/dL for momelotinib and to 8.7 g/dL from 7.5 g/dL for danazol (Supplementary Fig. S2), with patients treated with momelotinib consistently having higher mean levels of hemoglobin than those treated with danazol. However, after crossing over to open-label momelotinib at Week 24, mean hemoglobin levels in the danazol group increased from 7.7 to 9.5 g/dL after 20 weeks.

No new safety signals were identified in this sub-analysis compared with the overall intention-to-treat (ITT) cohort of the MOMENTUM trial (Table 3). During the 24-week randomized period, all patients reported at least one TEAE, most commonly constipation, hyperkalemia, nausea, peripheral edema, and pruritis (17.6% [3/17] each across both groups).

In the momelotinib group, the most common TEAEs were peripheral edema, diarrhea, dizziness, fluid overload, hyperuricemia, and vomiting (18.2% [2/11] each). In the danazol group, constipation, hyperkalemia, nausea, pruritis, and increased alanine aminotransferase, aspartate aminotransferase, and blood creatinine were the most common TEAEs (33.3% [2/6] each).

Grade ≥ 3 TEAEs were reported in 36.4% (4/11) and 66.7% (4/6) of the momelotinib and danazol groups, respectively, including fluid overload in 18.2% (2/11) of patients in the momelotinib group; one patient in the momelotinib group reported grade ≥ 3 anemia. No patients reported grade ≥ 3 thrombocytopenia or peripheral neuropathy.

TEAEs led to treatment interruption and/or dose reduction in 18.2% (2/11) and 16.7% (1/6) of patients in the momelotinib and danazol groups, respectively. TEAEs led to discontinuation of the study treatment in two patients in the danazol group: one experienced increased alanine aminotransferase and the other experienced increased aspartate aminotransferase.