by Dr. C.H. Weaver M.D. updated 5/2019
The agent Jakafi® (ruxolitinib) has demonstrated significant improvements in long-term outcomes for patients diagnosed with myelofibrosis. These results were recently presented at the 2016 annual meeting of the American Society of Clinical Oncology (ASCO).(1)
Myelofibrosis (MF) is a type of blood cancer known as a myeloproliferative neoplasm that is chronic and progressive in nature. It involves the abnormal development and function of bone marrow cells that produce blood cells, and leads to the formation of scar tissue in the bone marrow. When the bone marrow becomes scarred, it is not able to produce adequate amounts of blood cells.
Myelofibrosis can cause anemia, enlargement of the spleen and liver, fatigue, and other problems. In some patients with MF, the condition progresses to acute myeloid leukemia, which is an aggressive type of leukemia. Myelofibrosis is rare and affects ~18,000 people in the U. S. Although it can occur at any age, it most commonly occurs in individuals over 65.
When MF develops on its own (and not as the result of another bone marrow disease), it’s called primary myelofibrosis. Myelofibrosis can also result from a worsening of other bone marrow diseases, such as polycythemia vera and essential thrombocythemia.
The JAK1/JAK2 cellular pathway has demonstrated activity involved in the progression of MF. Subsequently, researchers have developed agents that block the activity of the JAK1/JAK2 pathway, reducing or halting the negative effects caused by its activity.
Long-term results from a trial referred to as the COMFORT 1 trial, were recently evaluated to determine the ongoing effectiveness of Jakafi as treatment for MF. The trial included 309 patients with MF; one group was initially treated with Jakafi, and the other group received a placebo (inactive substitute) as initial therapy. The patients who received placebo were allowed to cross over to the Jakafi group and receive treatment with Jakafi at a specified time period, or if the volume of their spleen continued to increase.
The follow-up time period of the COMFORT 1 trial reported at this year’s ASCO was 5 years.
- At approximately 6 months following the initiation of therapy, the mean reduction in spleen volume among patients initially treated with Jakafi was 31.6%; the median duration of a spleen volume reduction of at least 35% was approximately 3.5 years.
- At 5 years, the median overall survival for patients initially treated with Jakafi has not yet been reached.
- Overall survival at 5 years, however, was significantly improved among patients initially treated with Jakafi, compared to those who initially received placebo, despite the fact that all patients were ultimately allowed to receive treatment with Jakafi.
- After 6 months on therapy with Jakafi, mean levels of hemoglobin (portion of red blood cells) and platelets remained stable for approximately 5 years.
- Jakafi was generally well tolerated.
These results demonstrate that Jakafi provides significant improvements in long-term outcomes among patients with myelofibrosis, even at 5 years following initiation of therapy.
Durable responses, such as spleen volume reduction, hemoglobin and platelet levels, as well as survival improvement, provide evidence of Jakafi’s effectiveness in MF. Continued evaluation of optimal use of Jakafi in patients with MF is ongoing.
Hydroxyurea in combination with Jakafi yielded a high clinical response rate in patients with hyperproliferative types of myelofibrosis.
A multi-center, observational study by Dr Pugliese and colleagues from the Department of Medicine and Surgery, Hematology and Hematopoietic Stem Cell Transplant Center, University of Naples Federico II, Italy, included 20 adults with intermediate- or high-risk primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF with hyperproliferative manifestations. These patients were given a combination therapy comprising Jakafi and Hydrea (hydroxyurea).(2)
A total of 8 (40%) patients had clinical responses of any type during Jakafie\, whereas 17 (85%) had clinical responses during therapy with the Jakafi–Hydrea combination. After a median of 12.4 months, 16 of 20 patients receiving the combination had a hematologic response.
No clear survival advantages was established however longer follow up is necessary to determine the ultimate effectiveness of the combination.
- Gupta V, Verstovsek S, Mesa R, et al. Long-term outcomes of Jakafi (RUX) therapy in patients (pts) with myelofibrosis (MF): 5-year update from COMFORT-I. Proceedings from the 2016 annual meeting of the American Society of Clinical Oncology (ASCO). Abstract #1712.
- Cancer Med. 2019 Apr 17. Epub ahead of print.