Jean-Jacques Kiladjian, MD, PhD, professor of clinical pharmacology, Paris Diderot University, consultant hematologist, head, Clinical Investigation Center, Saint-Louis Hospital, Paris, France, discusses the potential utility of momelotinib in improving transfusion-independence rates in myelofibrosis. 

2021 European Hematology Association Congress

, findings from a subset analysis of the phase 3 SIMPLIFY-1 trial (NCT01969838) were presented in a virtual poster. The results demonstrated that treatment with momelotinib resulted in higher rates of transfusion independence at 24 weeks compared with treatment with ruxolitinib (Jakafi) in patients with JAK inhibitor–naïve myelofibrosis. Notably, this benefit was observed irrespective of baseline anemia, baseline platelet count, or baseline transfusion status.

Typically, patients with JAK inhibitor–naïve myelofibrosis are treated with ruxolitinib, says Kiladjian. However, ruxolitinib is associated with thrombocytopenia, so patients often have to dose reduce or stop treatment with ruxolitinib, Kiladjian explains. This limits the efficacy of ruxolitinib in terms of symptom control for splenomegaly and anemia, Kiladjian says.

Patients seem able to tolerate an effective dose of momelotinib without dose-limiting thrombocytopenia, which could allow them to derive splenic responses and transfusion independence, Kiladjian concludes.

Videos

Jean-Jacques Kiladjian, MD, PhD, discusses the potential utility of momelotinib in improving transfusion-independence rates in myelofibrosis.  



Dr. Kiladjian on Improving Transfusion-Independence Rates With Momelotinib in Myelofibrosis   

Jean-Jacques Kiladjian, MD, PhD, discusses data from the following presentation:

Improved Transfusion Independence Rates for Momelotinib vs Ruxolitinib in Anemic JAKi Naïve Myelofibrosis Patients are Independent of Baseline Platelet or Transfusion Status (Kiladjian, EHA 2021, EP1081)

The objective of this study is to report transfusion independence results from the SIMPLIFY-1 trial (NCT01969838) in JAK inhibitor–naïve patients with myelofibrosis who were treated with momelotinib (MMB) vs ruxolitinib (RUX).

Phase 3, double-blind trial with 1:1 randomization to MMB or RUX (N = 432)

MMB is an inhibitor of JAK1, JAK2, and ACVR1/ALK2; RUX is a JAK1 and JAK2 inhibitor

Week 24 (W24) transfusion independence (TI) response rate: 67% on MMB vs 49% on RUX

Median overall survival: 53 months in the RUX arm, not reached in the MMB arm

Treatment with MMB resulted in higher TI rates vs RUX in all patient subsets with baseline (BL) hemoglobin (Hgb) ≤ 14 g/dL, and in all subsets defined by BL platelets (PLTs) and by BL transfusion status.

Transfusion requiring (neither transfusion dependent [TD] nor TI): 53% MMB vs 31% RUX

Data suggest that an MMB-mediated TI response at week 24 is associated with a survival advantage.

These data support the potential benefit of MMB’s ACVR1/ALK2 inhibitor activity in addition to inhibiting JAK1 and JAK2.

Jean-Jacques Kiladjian, MD, PhD, describes updated results presented at the European Hematology Association 2021 Virtual Congress from the phase 3 SIMPLIFY-1 trial of momelotinib vs ruxolitinib in JAK inhibitor–naïve patients with myelofibrosis.

Rapid Readouts: Updated Results From the Phase 3 SIMPLIFY-1 Trial

Jean-Jacques Kiladjian, MD, PhD, professor of clinical pharmacology, Paris Diderot University, consultant hematologist, head, Clinical Investigation Center, Saint-Louis Hospital, Paris, France, discusses, the potential utility of momelotinib in myelofibrosis. 

During the 2021 ASCO Annual Meeting and the EHA 2021 Virtual Congress, findings from an analysis of the phase 3 SIMPLIFY 1 trial (NCT01969838) were presented, showing that patients who achieved transfusion independence after 24 weeks of momelotinib treatment derived clinical benefit irrespective of the degree of anemia, platelet count, or transfusion status at baseline.

As such, the data suggest that patients with myelofibrosis could benefit from JAK inhibitor optimization based on specific disease characteristics, Kiladjian says. For example, patients with severe thrombocytopenia may be better suited for momelotinib because they may not benefit from a maximized dose of ruxolitinib (Jakafi), Kiladjian explains. Conversely, patients with high platelet counts could be treated with ruxolitinib in the frontline setting because momelotinib was found to be noninferior to ruxolitinib regardless of baseline platelet counts, Kiladjian concludes.

Jean-Jacques Kiladjian, MD, PhD, discusses, the potential utility of momelotinib in myelofibrosis.  



Dr. Kiladjian on the Potential Utility of Momelotinib in Myelofibrosis 

Jean-Jacques Kiladjian, MD, PhD, professor of clinical pharmacology, Paris Diderot University, consultant hematologist, head, Clinical Investigation Center, Saint Louis Hospital, Paris, France, discusses the RUXOPeg trial in myelofibrosis.

The RUXOPeg trial examined the combination of ruxolitinib (Jakafi) and pegylated interferon alfa-2a (Pegasys) in patients with myelofibrosis, explains Kiladjian. Although ruxolitinib has not been shown to affect the disease history of myelofibrosis, interferon has demonstrated reduced molecular response and clinicohematologic responses. However, the agent has a high toxicity profile, says Kiladjian. If ruxolitinib’s anti-inflammatory properties could counteract the toxicity of interferon, it was believed that the combination could improve the rate of molecular response and clinicohematologic responses.

According to results presented at the 2018 ASH Annual Meeting, the combination was well tolerated. In the first 16 patients enrolled in this study, there were no dose-limiting toxicities, says Kiladjian. Based on these results, investigators are planning to proceed to the second part of the study, which will randomize patients to the 2 highest dose combinations in order to further assess the combination’s efficacy.

Dr. Kiladjian on the RUXOPeg Trial in Myelofibrosis

Jean-Jacques Kiladjian, MD, PhD, professor of clinical pharmacology, Paris Diderot University, consultant hematologist, head, Clinical Investigation Center, Saint Louis Hospital, Paris, France, discusses a study of ruxolitinib (Jakafi) and pegylated interferon alfa 2a in patients with myeloproliferative neoplasms, specifically myelofibrosis.

Myelofibrosis is a disease associated with splenomegaly, anemia, and bone marrow fibrosis, among other symptoms. In the RUXOPeg study, a phase I/II trial presented at the 2018 ASH Annual Meeting, patients of high- and intermediate-risk categories were treated with interferon and the JAK inhibitor ruxolitinib. Preliminary data showed that the combination had promising efficacy and a favorable toxicity profile.

In 15 evaluable patients, the median spleen size was 6 cm by palpation and 18 cm by imaging. No dose-limiting toxicities were observed in the patients, with the highest tolerated dose being ruxolitinib at 15 mg twice daily plus interferon at 135 mcg per week. The next phase of the study will evaluate ruxolitinib at 20 mg twice daily.

Jean-Jacques Kiladjian, MD, PhD, professor of clinical pharmacology, Paris Diderot University, consultant hematologist, head, Clinical Investigation Center, Saint Louis Hospital, Paris, France, discusses a study of ruxolitinib and pegylated interferon alpha 2a in patients with myeloproliferative neoplasms.

Jean-Jacques Kiladjian, MD, PhD, Saint-Louis Hospital (AP-HP)

Articles

Dr. Kiladjian on Improving Transfusion-Independence Rates With Momelotinib in Myelofibrosis

Rapid Readouts: Updated Results From the Phase 3 SIMPLIFY-1 Trial

Dr. Kiladjian on the Potential Utility of Momelotinib in Myelofibrosis

Dr. Kiladjian on the RUXOPeg Trial in Myelofibrosis

Dr. Kiladjian on Ruxolitinib Plus Interferon in MPNs