Treatment with JAK inhibitor in myelofibrosis may depend on the line of treatment and the risk of AE

The data offer new insight, as comparable data on drug class are sparse despite the approval of 2 JAK inhibitors for use in myelofibrosis and other promising ones.

The researchers shared the results of a meta-analysis comparing the efficacy and tolerability of various Janus kinase (JAK) inhibitors in myelofibrosis. The results offer guidance for the use of JAK inhibitors in this setting and suggest that the choice of an inhibitor may depend on the line of treatment and the risk of adverse events such as severe anemia and / or thrombocytopenia.

The data also offer new insights, as comparable treatment class data is sparse despite the approval of 2 JAK inhibitors for use in myelofibrosis and others that have shown benefit. Ruxolitinib has been approved for a decade for the treatment of intermediate 2 or high risk primary or secondary myelofibrosis, and federatinib was recently approved in 2019 for the same patients.

“All JAK inhibitors have shown a significant effect on reducing splenomegaly compared to placebo, the best available treatment or ruxolitinib in different clinical trials,” the researchers noted. “It is interesting to note that tolerance and adverse events appear to be different depending on the JAK inhibitors. However, there is a lack of data regarding the direct comparison of anti-JAKs with each other.

In the absence of direct comparisons between JAK inhibitors, the researchers collected data from 7 studies, including nearly 2,000 patients receiving 1 of the 2 approved JAK inhibitors, pacritinib or momelotinib. The results support the use of ruxolitinib as the gold standard JAK inhibitor for these patients while also suggesting that federatinib is a viable first-line alternative to ruxolitinib.

Fedratinib and momelotinib have both shown similar efficacy to ruxolitinib, with fedratinib demonstrating a comparable reduction in splenomegaly and improvement in disease-related symptoms. The treatment was also less toxic to the platelets than ruxolitinib.

“Among the investigational agents, momelotinib as first- or second-line treatment after ruxolitinib appears to be an attractive option for reducing splenomegaly, although it has not been possible to obtain results on its relative efficacy on constitutional symptoms, ”the researchers explained.

They added that momelotinib may also be a viable option when the onset of severe anemia is a concern. Throughout the studies, treatment was associated with significantly lower rates of grade 3/4 anemia compared to the other 3 JAK inhibitors. According to the group, this could be due to the treatment’s ability to decrease the production of hepcidin.

Meanwhile, the researchers say, pacritinib appeared to be less effective than ruxolitinib in the first line setting, but showed promise in the second line setting after treatment with ruxolitinib. The researchers wrote: “Regarding pacritinib, our results showed better efficacy in reducing spleen size in patients previously exposed to ruxolitinib than in patients naïve to JAK inhibitors.

Reference

Elder L, Orvain C, Ianotto J, et al. Efficacy and tolerability of Janus kinase inhibitors in myelofibrosis: a systematic review and a network meta-analysis. Blood cancer J. 2021; 11 (7): 135. doi: 10.1038 / s41408-021-00526-z


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