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. 2020 Sep 25;16:889–901. doi: 10.2147/TCRM.S258704

Table 3.

Summary of momelotinib safety from clinical trials

Trials
NCT00935987 7-year follow-up NCT00935987 SIMPLIFY-1 NCT01969838 SIMPLIFY-2 NCT02101268
≥ Grade 3 hematologic adverse event

  • Thrombocytopenia (32%)

  • Neutropenia (3%)

  • Anemia (3%)

  • Thrombocytopenia (24%)

  • Neutropenia (9%)

  • Anemia (5%)

 Mmb vs Rux

  • Thrombocytopenia (7% vs 4.6%)

  • Anemia (5.6% vs 23.1%)

  • Neutropenia (2.8% vs 4.6%)

 Mmb VS BAT

  • Thrombocytopenia

Seven (7%) vs three (6%)

  • Anemia

14 (14%) vs seven (14%)
≥ Grade 3 nonhematologic adverse event

  • Hyperlipasemia (5%)

  • Increased ALT (3%)

  • Increased AST (3%)

  • Headache (3%)

  • Hyperlipasemia (7%)

  • Increased ALT (4%)

  • Increased AST (2%)

  • Headache (2%)

  • Increased ALP (2%)

  • Hypertension (2.8% vs 4.2%)

 Mmb vs BAT

  • Abdominal pain

One (1%) vs 3 (6%)
Gastrointestinal side effects Most commonly noted:
Nausea (18%)
Diarrhea (13%)
Severity grade 1–2 and self-limiting, not requiring dose reduction or discontinuation		 All grade 1 or 2:
Nausea (23%)
Diarrhea (20%)
Increased amylase (17%)		 4.6% of patients had at least grade 3 diarrhea
Treatment-emergent adverse events occurring in >10% included nausea (34%), abdominal pain (22%)		 Mmb vs BAT

  • Diarrhea 32 (31%) grade 1/2, two (2%) grade 3 vs 7 (14%) grade 1/2, one (2%) grade 3

  • Nausea 18 (17%) grade 1/2, two (2%) grade 3 vs four (8%) grade 1/2, one (2%) grade 3

  • Abdominal pain 15 (14%) grade 1/2 and one (1%) grade 3 vs five (10%) grade 1/2 and three (6%) grade 3

  • Constipation 12 (12%) vs two (5%), both grade 1/2
Peripheral neuropathy
(PN)		 27% reported peripheral neuropathy (mostly grade 1), with 13 patients reporting it as new and three patients reporting it as worsening or preexisting symptoms. Six
of these (38%) had previous exposure to immunomodulators or JAK-inhibitor treatment. Median time to onset of symptoms was 141 days. Eight (50%)
had complete resolution of symptoms by the end of the trial, despite continuing CYT387.
Seven patients (15%)
47% had
grade 1 or 2 peripheral neuropathy		 Mmb arm: PN noted in 22 patients (10.3%) with 28 adverse events compared to ten patients (4.6%) with eleven adverse events in Rux arm. Two patients receiving Mmb reported PN at baseline compared to one patient receiving Rux.
All adverse events were grade 1–2, except for one episode of peripheral sensory neuropathy in Rux arm. PN did not lead to discontinuation of treatment.
PN was most commonly reported as peripheral sensory neuropathy, with peripheral motor neuropathy occurring only with Mmb.		 15 events of peripheral neuropathy reported in eleven (11%) of patients, all grade 1 or 2 except one case of grade 3 in patients receiving Mmb, two of whom had PN at baseline, compared to 0 patients in BAT group.
Three (3%) patients discontinued Mmb due to PN (one resolved case of sensory neuropathy, one ongoing case of peripheral sensorimotor neuropathy, and one case of polyneuropathy).
Dose reductions 16 patients (33%) needed dose reduction, occurring more frequently in patients receiving 300mg than those receiving 150mg. Five patients needed dose reductions due to peripheral neuropathy. There was no clear pattern identified during analysis of adverse events for the remainder. Not discussed in study 26% Mmb arm compared to 56% Rux arm needed dose reductions or interruptions (most commonly for adverse events — 17.3% and 25.6%, respectively). 60 (58%) patients receiving Mmb required dose reduction. Discontinuation of BAT was inconsistently reported, due to changes in therapy or intentional no therapy options available for this group.
Dose-limiting toxicities Grade 3 headache (n=1)
Grade 3 hyperlipasemia (n=1)
Both reversible on drug discontinuation		 Grade 3 headache
Grade 3 hyperlipasemia		 Reported for 17.8% in Mmb arm and 36.6% in Rux arm 17 (16%) patients receiving Mmb needed dose reduction.
Nine (17%) PN patients receiving BAT needed dose reduction due to adverse events.
Acute leukemic transformation Not discussed in study On study: three leukemic transformations
During 7-year follow-up, 15 patients had leukemic transformations occurring at median of 3.6 years		 Mmb: one patient (grade 4)
Rux: two patients (grades 3 and 5)		 Mmb: two patients grade 5, one patient grade 4
BAT: one patient grade 1
Death Total five deaths,
none related to CYT387		 On-study deaths: 15 patients
During 7-year follow-up: 73 deaths occurring at median of 2.5 years
ian survival from time of study is 3.2 years, with 5-r survival of 30%		 At reported follow-up:
Mmb: seven deaths (3.3%)
Rux: seven deaths (3.2%)		 At reported follow-up:
Mmb group: six patients (6%) had died, with two possibly related to Mmb therapy
Rux arm: four patients (7%) had died, not related to treatment
Reference 37 39 40 42

Abbreviations: JAK, janus kinase; Mmb, momelotinib; RBC, red blood cell; BAT, best alternative therapy; AST, aspartate aminotransferase; ALT, alanine aminotransferase; ALP, alkaline phosphatase; PN, peripheral neuropathy.