Ruxolitinib is a JAK1/2 inhibitor that is effective in managing symptoms and splenomegaly related to myelofibrosis (MF). Unfortunately, many patients must discontinue ruxolitinib, at which time treatment options are not well defined. In this study, we investigated salvage treatment options and clinical outcomes among MF patients who received and discontinued ruxolitinib outside the context of a clinical trial. Among 145 patients who received ruxolitinib, 23 died while on treatment, 58 remained on treatment at time of analysis, leaving 64 people available for analysis. Development of cytopenias was the most common reason for discontinuation (38%) after median treatment time of 3.8 months (mo). The majority of patients received some form of salvage therapy after ruxolitinib discontinuation (n = 42; 66%), with allogeneic hematopoietic stem cell transplant (alloHSCT) (n = 17), being most commonly employed. Lenalidomide, thalidomide, hydroxyurea, interferon, and danazol were used with similar frequency. The response rate to salvage treatment was 26% (8 responses) and responses were most often seen with lenalidomide or thalidomide. Improved outcomes were observed in patients who underwent alloHSCT or received salvage therapy compared to those who did not receive additional therapy. Median overall survival (OS) after ruxolitinib discontinuation was 13 months. These findings show that salvage therapy can provide clinical responses after ruxolitinib discontinuation; however, these responses are rare and outcomes in this patient population are poor. This represents an area of unmet clinical need in MF.
Acute myeloid leukemia (AML) was initially subdivided according to morphology (the French-American-British system), which proved helpful in pathologic categorization. Subsequently, clinical and genomic factors were found to correlate with response to chemotherapy and with overall survival. These included a history of antecedent hematologic disease, a history of chemotherapy or radiation therapy, the presence of various recurrent cytogenetic abnormalities, and, more recently, the presence of specific point mutations. This article reviews the biology and responses of one AML subgroup with consistent response and good outcomes following chemotherapy (core-binding factor leukemia), and two subgroups with persistently bad, and even ugly, outcomes (secondary AML and TP53-mutated AML).
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