Andrew Kuykendall, MD, is an assistant member in the Department of Malignant Hematology at the Moffitt Cancer Center in Tampa, Florida.

Andrew Kuykendall, MD, assistant member, the Department of Malignant Hematology, Moffitt Cancer Center, discusses the evaluation of momelotinib in patients with symptomatic and anemic myelofibrosis.

Momelotinib has demonstrated clinical benefit in the phase 3 SIMPLIFY 1 (NCT01969838) and SIMPLIFY 2 (NCT02101268) trials. SIMPLIFY 1, which evaluated momelotinib vs ruxolitinib (Jakafi), met its primary end point, showing that momelotinib was noninferior to ruxolitinib. The splenic response rates were 26.5% for momelotinib and 29% for ruxolitinib. SIMPLIFY 2 trial evaluated momelotinib vs best available therapy in anemic or thrombocytopenic patients with myelofibrosis. Although SIMPLIFY 2 produced a 26% total symptom score (TSS) response, spleen volume reductions of at least 35% were not achieved with momelotinib, prompting investigators to designed third phase 3 trial.

The phase 3 MOMENTUM trial (NCT04173494) evaluated momelotinib vs danazol in order to better identify patients who may derive a clinical benefit from momelotinib. The trial enrolled patients that had big spleens, had symptoms of anemia, and received prior treatment with ruxolitinib in some fashion but experienced toxicity or did not experience a full response, Kuykendall explains.

Danazol has been used in practice for patients with anemic myelofibrosis, and the study used TSS response, spleen response, and transfusion independence as key end points. Findings from MOMENTUM showed that momelotinib was associated with better TSS responses and spleen responses, as well as noninferiority in transfusion independence, compared with danazol, Kuykendall says.

The 24-week TSS response rate was 24.6% for momelotinib, compared with 9.2% for danazol. Additionally, 40% of patients in the momelotinib arm had a spleen volume reduction of at least 25%, and 23.1% experienced at least a 35% spleen volume reduction. In the danazol arm, those rates were 6.2% and 3.1%, respectively. Additionally, 31% of patients in the momelotinib arm were transfusion independent at week 24, vs 20% of patients in the danazol arm.

Videos

Andrew Kuykendall, MD, discusses the evaluation of momelotinib in patients with symptomatic and anemic myelofibrosis.

Dr. Kuykendall on the Evaluation of Momelotinib in Myelofibrosis

Andrew Kuykendall, MD, assistant member, the Department of Malignant Hematology, Moffitt Cancer Center, discusses treatment considerations with ruxolitinib (Jakafi) in myelofibrosis.

Although a need for more beneficial agents remains in myelofibrosis, clinicians currently have more options to consider when making treatment decisions, Kuykendall says. In the current era of myelofibrosis treatments, some options may be more beneficial for some patients than others, Kuykendall adds.

The RR6 model was created to help clinicians predict which patients treated with ruxolitinib may not benefit in the same way as others, allowing those patients to potentially be selected for a change of therapy or enrollment in a clinical trial, Kuykendall explains.

The key factors the RR6 model looks at include suboptimal ruxolitinib dosing, the need for transfusions, and a suboptimal spleen response, Kuykendall explains. If these characteristics are present, a patient may benefit more from a different therapy, Kuykendall concludes.

Andrew Kuykendall, MD, discusses treatment considerations with ruxolitinib in myelofibrosis.


Dr. Kuykendall on Treatment Considerations with Ruxolitinib in Myelofibrosis

Andrew Kuykendall, MD, assistant member, the Department of Malignant Hematology, Moffitt Cancer Center, discusses the evolution of prognostication factors in primary and secondary myelofibrosis.

The heterogeneous nature of myelofibrosis highlights the importance of disease prognostication at all stages, Kuykendall says. Although early prognostic models used over a decade ago were based on clinical factors such as white blood cell count, hemoglobin levels, platelets, age, constitutional symptoms, and circulating blasts, now, prognostication increasingly includes genetics, which drive much of the heterogeneity of this disease, Kuykendall explains. Newer prognostication models build on the clinical factors of past models by also including specific mutations and the number of mutations a patient has, Kuykendall notes.

Additionally, unique prognostic models have been developed for patients who have secondary myelofibrosis, which is myelofibrosis that occurs after prior essential thrombocythemia or polycythemia vera, Kuykendall says. Moving toward more individualized care has allowed for the evolution of increasingly effective treatment strategies, as well as a better understanding of each patient’s risk, Kuykendall concludes.

Andrew Kuykendall, MD, discusses the evolution of prognostication factors in primary and secondary myelofibrosis.

Andrew Kuykendall, MD

Articles

Dr. Kuykendall on the Evaluation of Momelotinib in Myelofibrosis

Dr. Kuykendall on Treatment Considerations with Ruxolitinib in Myelofibrosis

Dr. Kuykendall on Prognostication Factors in Myelofibrosis