While myelofibrosis (MF) patients with ruxolitinib (rux) failure continue to represent an unmet medical need, they also appear poised to benefit from a better understanding of molecular pathology of the disease and from new drug development, according a review published in the SOHO 2019 Meeting Proceedings Supplement in Clinical Lymphoma, Myeloma and Leukemia.
It is commonplace for rux failure to occur during treating MF as the is the result of complex, poorly understood pathogenesis. Rux failure predicts diminished survival and currently has no reliably effective treatment strategy. Despite frequent occurrence and scientific review, there remains an inconclusive definition of rux failure. According to the researcher, “a practical definition identifies failure occurring when the drug ceases to be effective and/or drug toxicity requires discontinuing medication or reduction of the dose to an ineffective level.”
To organize the necessary principals in treating MF patients, one should make a detailed characterization of both the clinical and pathological features of the patient’s disease at the time of diagnosis. This process includes defining the mutational genotype (MG) of the malignancy, generating an accurate prognostic score, deciding pertaining to propriety of allogenic hematopoietic stem cell transplant (AHSCT), and considering the sustainability of the patient for clinical trial intervention.
When developing considerations for treating rux failure, one should determine whether the chief problem is toxicity, decreased efficacy with resultant myeloproliferation, or both. The researcher further noted that “evaluation of a toxicity failure should include the ruling out of non-neoplastic contributors (e.g. micro-nutrients, a new drug interaction, blood loss, hemolysis, renal dysfunction related decrease in erythropoietin, hypo-androgen state, thyroid dysfunction) and consider reassessment of MG (often possible with peripheral blood). Evaluation of a myeloproliferative failure should again include rule out of non-neoplastic contributors (e.g. infection, altered rux pharmacology) and reassessment of MG.”
Moreover, it is prudent to use patterns of failure as a guide for selecting evaluation and treatment options of rux failure.
“We probably underutilize our internal medicine and hematology skills to identify and treat non-neoplastic and correctable contributors to the rux failure,” the research wrote in conclusion. “These chronically difficult MF cases also provide opportunities for collaborative care involving the general oncologist in the community, the MF clinical trialist and AHSCT specialist at the referral center.”