The treatment combination demonstrated an overall response rate of 44% and median overall survival of 9.5 months.
A phase 2 study assessing ruxolitinib and decitabine in patients with myeloproliferative neoplasms (MPNs) demonstrated that the treatment combination is well tolerated and elicits favorable overall survival (OS), according to the results published in Blood Advances.
These findings indicate the combination could be a viable treatment option for the high-risk group of patients.
Throughout September 2016 and March 2017, 25 patients were enrolled in the study. Follow-up showed that the treatment combination resulted in a median OS of 9.5 months (95% CI, 4.3-12.0) and the overall response rate was 44% (95% CI, 24.4%-65.1%), although this was not indicative of improved survival, the researchers noted.
According to the researchers, the survival data compare favorably with historical data showing a median OS of 3 to 5 months for conventional acute myeloid leukemia induction chemotherapy for these patients.
These patients included 15 in the blast phase (MPN-BP) of disease and 10 patients in the accelerated phase (MPN-AP) of disease, the latter of which typically has particularly poor outcomes.
“MPN-AP/BP is a genetically complex, treatment-resistant, and debilitating disease in dire need of improved interventions,” wrote the researchers, adding, “Outside of clinical trial options, this therapeutic approach should be considered in those patients with leukemic evolution of chronic MPN and may serve as a potential bridge to [hematopoietic stem cell transplantation (HCT)] in a subset of patient, which remains the only curative option.”
There were 2 patients in the current study who had incomplete platelet recovery and 9 who achieved a partial response. At the time of response assessment, 8 of the partial responders had a blast count of < 5% in the peripheral blood. There were no patients who achieved a complete response, and responses were not evaluable in 7 patients.
Assessment also showed that patients had a median reduction in spleen size of 70.5%.
The median number of cycles to best response was 4 cycles, which was also the median number of cycles administered for both groups of patients. Treatment cycles consisted of ruxolitinib 25 mg twice daily for the induction cycle followed by 10 mg twice daily for subsequent cycles in combination with decitabine 20 mg/m2 for 5 consecutive days in a 28-day cycle.
The most common treatment emergent adverse events of all grades experienced with the treatment combination included fatigue (32%), febrile neutropenia (28%), pneumonia (28%), diarrhea (28%), abdominal pain (24%), and edema (24%).
Since enrolling in the study, all patients have discontinued treatment, with reasons including adverse events (36%), disease progression (28%), physician decision (8%), HCT (8%), study disclosure (8%), patient withdrawal (4%), and unknown (8%). Nineteen patients died during follow-up.
“The combination of ruxolitinib and decitabine in MPN-AP/BP is a viable low-intensity, ambulatory regimen that reduces spleen size with a median OS that is particularly encouraging given multiple historical reports,” the authors concluded. “Outside of clinical trial options, this therapeutic approach should be considered in those patients with leukemic evolution of chronic MPN and may serve as a potential treatment bridge to HCT in a subset of patient, which remains the only curative option.”
Mascarenhas J, Rampal R, Kosiorek H, et al. Phase 2 study of ruxolitinib and decitabine in patients with myeloproliferative neoplasm in accelerated and blast phase. Blood Adv. 2020;4(20):5246-5256.