Deferasirox in the management of iron overload in patients with myelofibrosis treated with ruxolitinib: The multicentre retrospective RUX‐IOL study

Abstract

Summary Deferasirox (DFX) is used for the management of iron overload (IOL) in many haematological malignancies including myelofibrosis (MF). The ‘RUX‐IOL’ study retrospectively collected 69 MF patients treated with ruxolitinib (RUX) and DFX for IOL to assess: safety, efficacy in term of iron chelation response (ICR) and erythroid response (ER), and impact on overall survival of the combination therapy. The RUX–DFX therapy was administered for a median time of 12.4 months (interquartile range 3.1–71.2). During treatment, 36 (52.2%) and 34 (49.3%) patients required RUX and DFX dose reductions, while eight (11.6%) and nine (13.1%) patients discontinued due to RUX‐ or DFX‐related adverse events; no unexpected toxicity was reported. ICR and ER were achieved by 33 (47.8%) and 32 patients (46.4%) respectively. Thirteen (18.9%) patients became transfusion‐independent. Median time to ICR and ER was 6.2 and 2 months respectively. Patients achieving an ER were more likely to obtain an ICR also (p = 0.04). In multivariable analysis, the absence of leukocytosis at baseline (p = 0.02) and achievement of an ICR at any time (p = 0.02) predicted improved survival. In many MF patients, the RUX–DFX combination provided ICR and ER responses that correlated with improved outcome in the absence of unexpected toxicities. This strategy deserves further clinical investigation.

Iron chelation for myelofibrosis‐related anaemia during treatment with a Janus kinase inhibitor

“…The median duration of erythroid response was 26.9 months in those who had achieved both an erythroid and iron chelation response. A reduced transfusion burden should contribute to improved chelation response, and indeed these two responses were closely related, and both were associated with improved overall survival, although in multivariable analysis only iron chelation response remained statistically significant (hazard ratio 0.33, 95% confidence interval 0.13–0.83) 3 …”

“…There were 22 deaths during the observation period, with 16/22 (73%) attributed to leukaemic transformation or progressive MF without leukaemia. 3 Erythroid responses (reduced transfusion requirement) were seen in 46% of patients, including 13 (19%) who became transfusion-independent. The median time to erythroid response was 2 months, whereas the median time to chelation response was 6 months.…”

“…3 Patients who achieved an iron chelation response had fewer units of red cells transfused prior to commencing ruxolitinib (p = 0.04), a lower serum ferritin at diagnosis (p = 0.05), a longer time between diagnosis and commencement of deferasirox (p = 0.06), and more often had a triple-negative (JAK2/calreticulin [CALR]/myeloproliferative leukaemia protein [MPL]) mutation status (p = 0.07). 3 Without correction for multiple testing, none of these parameters can be considered statistically significant predictors. However, it is noteworthy that the erythroid-related parameters all pertain to measures of disease before the introduction of chelation treatment, arguing that it may be underlying disease biology that determines erythroid response and survival, rather than treatment-related factors.…”

“…A reduced transfusion burden should contribute to improved chelation response, and indeed these two responses were closely related, and both were associated with improved overall survival, although in multivariable analysis only iron chelation response remained statistically significant (hazard ratio 0.33, 95% confidence interval 0.13-0.83). 3 Patients who achieved an iron chelation response had fewer units of red cells transfused prior to commencing ruxolitinib (p = 0.04), a lower serum ferritin at diagnosis (p = 0.05), a longer time between diagnosis and commencement of deferasirox (p = 0.06), and more often had a triple-negative (JAK2/calreticulin [CALR]/myeloproliferative leukaemia protein [MPL]) mutation status (p = 0.07). 3 Without correction for multiple testing, none of these parameters can be considered statistically significant predictors.…”

“…Patients who achieved an iron chelation response had fewer units of red cells transfused prior to commencing ruxolitinib ( p = 0.04), a lower serum ferritin at diagnosis ( p = 0.05), a longer time between diagnosis and commencement of deferasirox ( p = 0.06), and more often had a triple‐negative (JAK2/calreticulin [CALR]/myeloproliferative leukaemia protein [MPL]) mutation status ( p = 0.07) 3 . Without correction for multiple testing, none of these parameters can be considered statistically significant predictors.…”