LONG TERM SAFETY OF MOMELOTINIB IN JAK INHIBITOR NAÏVE AND PREVIOUSLY JAK INHIBITOR TREATED INTERMEDIATE/HIGH RISK MYELOFIBROSIS PATIENTS
Author(s): ,
Claire Harrison
Affiliations:
Guy's and St. Thomas' NHS Foundation Trust,London,United Kingdom
,
Björn Andreasson
Affiliations:
NU Hospital Group,Uddevalla,Sweden
,
Nathalie Cambier
Affiliations:
CHU,Lille,France
,
Aaron T Gerds
Affiliations:
Cleveland Clinic Department of Hematology and Medical Oncology,Avon,United States
,
Sebastian Grosicki
Affiliations:
Medical University of Silesia,Katowice,Poland
,
Árpád Illés
Affiliations:
University of Debrecen,Debrecen,Hungary
,
Jean-Jacques Kiladjian
Affiliations:
Saint-Louis Hospital (AP-HP),Paris,France
,
David Lavie
Affiliations:
Hadassah-Hebrew University Medical Center,Jerusalem,Israel
,
Ruben Mesa
Affiliations:
UT Health San Antonio Cancer Center,San Antonio,United States
,
Jeanne Palmer
Affiliations:
Mayo Clinic Hospital,Phoenix,United States
,
Francesco Passamonti
Affiliations:
University of Insubria,Varese,Italy
,
Andrew Perkins
Affiliations:
Monash University,Melbourne,Australia
,
Tomasz Sacha
Affiliations:
Jagiellonian University,Kraków,Poland
,
Christof Scheid
Affiliations:
University of Cologne,Köln,Germany
,
Doroteya Todorieva-Todorova
Affiliations:
Hematology Division, Medical University,Pleven,Bulgaria
,
Alessandro M Vannucchi
Affiliations:
AOU Careggi, University of Florence,Florence,Italy
,
Tomasz Woźny
Affiliations:
Szpital MSWiA w Poznaniu,Poznań,Poland
,
Barbara J Klencke
Affiliations:
Sierra Oncology Inc.,Vancouver,Canada
,
Mark M Kowalski
Affiliations:
Sierra Oncology Inc.,Vancouver,Canada
Srdan Verstovsek
Affiliations:
The University of Texas MD Anderson Cancer Center,Houston,United States
(Abstract release date: 05/14/20) EHA Library. Harrison C. 06/12/20; 293602; EP1113
Prof. Dr. Claire Harrison
Prof. Dr. Claire Harrison
Contributions
Abstract

Abstract: EP1113

Type: e-Poster

Background
Momelotinib (MMB) is a potent JAK1, JAK2 and ACVR1 inhibitor with demonstrable clinical activity against each of the three hallmark features of myelofibrosis (MF), namely anemia, constitutional symptoms and splenomegaly, across the continuum of intermediate/high risk MF patients whether JAKi-naïve or advanced, previously JAKi-treated. Over 820 MF patients have received MMB during the compound’s clinical development program, including a number with treatment duration ranging up to 9 years.

Aims
This analysis was conducted to characterize the long-term safety of MMB, given the noteworthy durability observed in long-term responders from early clinical studies and in patients in the Phase 3 SIMPLIFY trials.  

Methods
Safety and tolerability data were analyzed from the extended treatment (XT) periods of the previously conducted Phase 3 SIMPLIFY-1 & -2 clinical trials (S1, S2). S1 was conducted in intermediate/high risk JAKi-naïve MF patients (n=432) randomized 1:1 to MMB or ruxolitinib (RUX) over a 24-week dosing period. S2 was conducted in prior RUX-treated MF patients with hematological toxicity (n=156) randomized 2:1 to MMB or best available therapy (BAT; consisting of RUX in 88% of patients). In both trials, patients originally randomized to MMB could continue MMB therapy (MMB→MMB) and those randomized to RUX/BAT were eligible to cross-over to MMB (RUX/BAT→MMB) for the additional XT period.

Results
MMB exhibits a very favorable safety profile during extended administration with low rates of high-grade hematological toxicities, consistent with its low myelosuppressive potential and net anemia benefit. Preliminary data from the XT period of S1 show the most commonly reported Grade 3/4 adverse events possibly related to study drug (rG3/4 AEs) in the MMB→MMB patients were anemia and thrombocytopenia (4.7% each), pneumonia (2.3%) and neutropenia (1.8%) and in the RUX→MMB patients were thrombocytopenia (8.6%), anemia (2.5%) and neutropenia (2.0%). These latter results contrast with the tolerability of RUX in the preceding randomized period where a significant rate of high grade anemia was observed (18.5%). In the XT period of S2, the most commonly reported rG3/4 AEs in the MMB→MMB group were anemia and thrombocytopenia (3.1% each). In the BAT→MMB group, the most commonly reported rG3/4 AEs were thrombocytopenia (15.0%), asthenia (10.0%) and anemia and neutropenia (5.0% each). Preliminary analysis of the long-term safety data indicates no new safety signals or evidence of cumulative toxicity for MMB in the XT periods, including low rates of cataracts, non-melanoma skin cancers and opportunistic infections. Consistent with previously reported S1 & S2 data, rates of unresolved peripheral neuropathy also remain low.

Conclusion
MMB displays very favorable long-term tolerability, including an absence of significant rates of high-grade hematological and other toxicities, consistent with its differentiated pharmacological and clinical profile. The compound’s low myelosuppressive potential and demonstrable anemia benefit enable sustained dose intensity in contrast to RUX, where toxicity-induced dose reductions are common. Notably, patients switching from RUX or BAT also experienced favorable MMB tolerability, despite their previous therapy. Consequently, a significant cohort of patients have benefited from extended MMB therapy without cumulative toxicity, confirming MMB’s ability to safely and effectively address the unmet needs of both JAKi-naïve and advanced, previously JAKi-treated intermediate/high risk MF patients.

Session topic: 16. Myeloproliferative neoplasms - Clinical

Keyword(s): Anemia, Janus Kinase inhibitor, Myelofibrosis

Abstract: EP1113

Type: e-Poster

Background
Momelotinib (MMB) is a potent JAK1, JAK2 and ACVR1 inhibitor with demonstrable clinical activity against each of the three hallmark features of myelofibrosis (MF), namely anemia, constitutional symptoms and splenomegaly, across the continuum of intermediate/high risk MF patients whether JAKi-naïve or advanced, previously JAKi-treated. Over 820 MF patients have received MMB during the compound’s clinical development program, including a number with treatment duration ranging up to 9 years.

Aims
This analysis was conducted to characterize the long-term safety of MMB, given the noteworthy durability observed in long-term responders from early clinical studies and in patients in the Phase 3 SIMPLIFY trials.  

Methods
Safety and tolerability data were analyzed from the extended treatment (XT) periods of the previously conducted Phase 3 SIMPLIFY-1 & -2 clinical trials (S1, S2). S1 was conducted in intermediate/high risk JAKi-naïve MF patients (n=432) randomized 1:1 to MMB or ruxolitinib (RUX) over a 24-week dosing period. S2 was conducted in prior RUX-treated MF patients with hematological toxicity (n=156) randomized 2:1 to MMB or best available therapy (BAT; consisting of RUX in 88% of patients). In both trials, patients originally randomized to MMB could continue MMB therapy (MMB→MMB) and those randomized to RUX/BAT were eligible to cross-over to MMB (RUX/BAT→MMB) for the additional XT period.

Results
MMB exhibits a very favorable safety profile during extended administration with low rates of high-grade hematological toxicities, consistent with its low myelosuppressive potential and net anemia benefit. Preliminary data from the XT period of S1 show the most commonly reported Grade 3/4 adverse events possibly related to study drug (rG3/4 AEs) in the MMB→MMB patients were anemia and thrombocytopenia (4.7% each), pneumonia (2.3%) and neutropenia (1.8%) and in the RUX→MMB patients were thrombocytopenia (8.6%), anemia (2.5%) and neutropenia (2.0%). These latter results contrast with the tolerability of RUX in the preceding randomized period where a significant rate of high grade anemia was observed (18.5%). In the XT period of S2, the most commonly reported rG3/4 AEs in the MMB→MMB group were anemia and thrombocytopenia (3.1% each). In the BAT→MMB group, the most commonly reported rG3/4 AEs were thrombocytopenia (15.0%), asthenia (10.0%) and anemia and neutropenia (5.0% each). Preliminary analysis of the long-term safety data indicates no new safety signals or evidence of cumulative toxicity for MMB in the XT periods, including low rates of cataracts, non-melanoma skin cancers and opportunistic infections. Consistent with previously reported S1 & S2 data, rates of unresolved peripheral neuropathy also remain low.

Conclusion
MMB displays very favorable long-term tolerability, including an absence of significant rates of high-grade hematological and other toxicities, consistent with its differentiated pharmacological and clinical profile. The compound’s low myelosuppressive potential and demonstrable anemia benefit enable sustained dose intensity in contrast to RUX, where toxicity-induced dose reductions are common. Notably, patients switching from RUX or BAT also experienced favorable MMB tolerability, despite their previous therapy. Consequently, a significant cohort of patients have benefited from extended MMB therapy without cumulative toxicity, confirming MMB’s ability to safely and effectively address the unmet needs of both JAKi-naïve and advanced, previously JAKi-treated intermediate/high risk MF patients.

Session topic: 16. Myeloproliferative neoplasms - Clinical

Keyword(s): Anemia, Janus Kinase inhibitor, Myelofibrosis

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