Between a rux and a hard place: evaluating salvage treatment and outcomes in myelofibrosis after ruxolitinib discontinuation

Abstract

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.

Life after ruxolitinib: Reasons for discontinuation, impact of disease phase, and outcomes in 218 patients with myelofibrosis

“…13 A second study of 64 patients treated in a real-life comparison confirmed that responses to salvage treatments are rare. 14 Understanding that the outcome after ruxolitinib is important for identifying patients who may benefit from specific interventions, such as allogeneic stem cell transplantation, 15 second-generation JAK inhibitors, [16][17][18] drugs with alternative mechanisms of action, 19,20 or investigational agents in combination with ruxolitinib. 21 Here, we report the outcome of 218 patients after ruxolitinib.…”

Survival outcomes in myelofibrosis patients treated with ruxolitinib: A population‐based cohort study in Sweden and Norway

“…1 There is limited evidence to show that ruxolitinib improves survival outcomes by modifying the disease course, although its effect on metabolic and nutritional variables may translate into survival benefits. 9 Eventually, most patients discontinue treatment due to adverse events or lack of efficacy. 9 In recent phase-III studies, about 50% of patients discontinued ruxolitinib within 3 years of treatment.…”

“…9 Eventually, most patients discontinue treatment due to adverse events or lack of efficacy. 9 In recent phase-III studies, about 50% of patients discontinued ruxolitinib within 3 years of treatment. 7 Salvage therapy options remain scarce 10 and mostly include allogeneic stem cell transplantation (allo-SCT) followed by immunomodulators; however, prognosis is unfavourable.…”

“…7 Salvage therapy options remain scarce 10 and mostly include allogeneic stem cell transplantation (allo-SCT) followed by immunomodulators; however, prognosis is unfavourable. 9 Although allo-SCT is the only curative treatment, it is rarely used in Sweden and Norway in this patient population due to the significant risk of morbidity and mortality. 11 Randomised controlled clinical trials are critical tools when assessing benefits of novel agents compared to standard of care.…”

Emerging translational science discoveries, clonal approaches, and treatment trends in chronic myeloproliferative neoplasms

“…62,63 Figure 5 in a qualified success with significant symptomatic benefit, but neither major change in the natural history nor a significant impact on the JAK2 V617F allelic burden, and a median survival of patients discontinuing ruxolitinib of 13-14 months. [67][68][69] The majority of other Type 1 JAK2 inhibitors have had their clinical development discontinued largely due to the emergence of serious neurotoxicity.…”