Momelotinib May Improve Survival and Quality of Life in MF

August 30, 2024

Leonardo Jaimes

Momelotinib appears to positively impact quality of life and overall survival in patients with myelofibrosis (MF), according to a recently published study in Frontiers in Oncology.

Most MF cases are associated with JAK or CALR mutations, which lead to an uncontrolled proliferation of stem cells and a decrease in the production of red blood cells (RBCs) and thrombocytes, the researchers noted.

Stem cell transplantation is currently the only curative alternative available for patients with MF. The advent of JAK inhibitors represented a significant advancement in symptom management, but patients often observed decreased efficacy after 3 years.

Anemia is largely responsible for the decrease in quality of life seen in patients with MF and represents an important cause of treatment discontinuation, as some of the treatments used in MF can contribute to the development of anemia.

“Anemia in MF is a complex condition resulting from factors such as displacement of erythropoietic tissue by fibrotic stroma, suboptimal environments in extramedullary sites, and splenomegaly-induced RBC sequestration,” the authors wrote.

Momelotinib is an effective JAK1/2 inhibitor that can successfully treat anemia in patients with MF, decreasing the need for transfusions. It can also prevent hepcidin synthesis, which in turn leads to increased iron circulation and increased erythropoiesis.

The effectiveness of momelotinib is supported by the results of the MOMENTUM trial; the double-blind included almost 200 patients who received either momelotinib or danazol to treat MF-associated anemia.  Results showed that patients who received were significantly less likely to require blood transfusions and have better Total Symptom Score than their counterparts.

Read more

Donor Type Impacts Survival in MF Cell Transplantation

Patients with myelofibrosis (MF) who receive hematopoietic cell transplantation (HCT) from a matched sibling donor appear to have better overall survival (OS) than those who receive transplants from other donor types, according to a recently published study in Blood Advances.

“Understanding the impact of donor type is crucial not only to improve the clinical outcomes with HCT but also to establish the donor pool with viable options and eventually improve access to HCT,” the authors wrote.

HCT is currently the only disease-modifying therapy available for MF, the study team noted. The outcome after transplantation is diverse and dependent on several disease- and patient-associated factors, they added. According to recent research, donor type could also influence the prognosis of patients with MF after HCT. One study showed that patients with matched sibling donors had a better OS than the rest.

However, previous research has not taken the impact of posttransplantation cyclophosphamide for graft versus host disease prophylaxis into consideration, the researchers noted. Furthermore, no patients in previous studies had received vHLA-haploidentical donor grafts, they continued.

Therefore, the authors aimed to assess the impact of donor type in OS, considering the factors above and using the Center for International Blood and Bone Marrow Transplant Research registry data for HCTs done between 2013 and 2019. The study included over 1000 patients who received HCTs for MF.

Results showed that similarly to previous findings, matched sibling transplants were associated with better overall survival and lower graft failure than the rest. However, OS was only superior to the rest in the first 90 days after transplant. There was no significant difference in OS among patients who received mismatched unrelated, matched unrelated, and haploidentical donor transplants.

Despite the findings, the authors remarked that HCTs should not be delayed in the search for fully matched donors and highlighted the need for solutions regarding graft failure.

Read more

Connecting Spleen Volume Reduction to Survival Outcomes in MF

Targeted Oncology Staff

CASE SUMMARY

A 68-year-old woman presented to her physician with symptoms of mild fatigue. Her spleen was palpable 6-7 cm below the left costal margin​, but she had no known comorbidities. Next-generation sequencing revealed a JAK2 V617F mutation​, and her karyotype was46XX.​ A bone marrow biopsy showed megakaryocyte proliferation and atypia with evidence of reticulin fibrosis​, and a blood smear was positive for leukoerythroblastosis​.

Her laboratory values also led to a diagnosis of primary myelofibrosis (MF). Risk stratification based on the dynamic international prognostic scoring system gave her a score of intermediate-1, and based on the mutation-enhanced international prognostic score system for transplantation-age she was also determined to be at intermediate risk​.

DISCUSSION QUESTIONS

  • Did the overall survival data from the COMFORT-I trial (NCT00952289) and COMFORT-II trial (NCT00934544) impact the way you manage patients with MF?​
  • How do you monitor and manage anemia in patients with primary MF prior to starting Janus kinase (JAK) inhibitor therapy?​

Read more