Myelofibrosis (MF) is an aggressive bone marrow malignancy characterized by an enlarged spleen, cytopenias, and reduced overall survival (OS). Ruxolitinib (RUX) is an approved first-line therapy for MF associated with intolerance and loss of response with chronic administration. However, reports have shown that patients who are diagnosed earlier in the low-risk category and those who initiated RUX ≤2 years from diagnosis had better responses to RUX compared with patients who were diagnosed in more advanced stages of disease and started RUX >2 years after diagnosis. RUX has also been extensively studied in clinical trials such as COMFORT-I and -II, which together established OS can be improved in patients who received RUX at the initiation of the study as well as those who received RUX after initially taking placebo or best available therapy.
The current investigation uses pooled data from 525 patients with a median age range of 65 to 70 years who were enrolled in the phase 3 COMFORT-I (RUX vs placebo) and COMFORT-II (RUX vs best available therapy) trials. Patients were grouped according to treatment type and/or duration: RUX for ≤12 months (n = 84), RUX for >12 months (n = 216), placebo/best available therapy for ≤12 months (n = 66), and placebo/best available therapy for >12 months (n = 159). Patients were diagnosed with intermediate-2 or high-risk MF. The analysis included frequency of thrombocytopenia (platelets <100 Gi/L or platelet transfusion) and anemia (hemoglobin <100 g/L or red blood cell transfusion), spleen volume response (SVR; spleen volume reduction ≥35% from baseline), symptom response (MF-Symptom Assessment Form total symptom score [TSS] reduction ≥50% from baseline; available in COMFORT-I only), and OS.
Fewer cases of thrombocytopenia and anemia could be observed as early as weeks 4 to 8 when RUX treatment was initiated within 12 months of diagnosis (18% thrombocytopenia, 59% anemia) compared with after 12 months (33% thrombocytopenia, 72% anemia). This effect was sustained over time. Patients who initiated RUX treatment earlier in the disease course (within 12 months of diagnosis) also had better SVR at weeks 24 and 48 (–35% and –36%, respectively), achieved ≥35% reduction from baseline SVR measurements at weeks 24 and 48 (48% and 44%, respectively), and achieved ≥50% reduction in TSS by week 24 (56%). Whereas median duration of SVR was not reached in patients with shorter disease course, those with longer disease progression reached maximum SVR at week 230. Mean change from baseline in TSS at week 24 was –52%. OS was improved in both RUX-treated groups compared with placebo and best available therapy. However, those patients treated with RUX within ≤12 months of disease progression demonstrated improved OS at week 240 compared with those whose RUX treatment began at >12 months (63% [95% confidence interval, 51%-73%] vs 57% [95% confidence interval, 49%-64%]; P = .0430).
The investigators recognize that younger age and higher baseline blood cell counts in this cohort may have influenced the final results of this investigation. However, it should be noted that these factors likely represent an earlier disease state, which further supports initiation of RUX therapy earlier in MF disease course may improve clinical outcomes and OS.
Source:
Verstovsek S, Kiladjian J-J, Vannucchi AM, et al. Does early intervention in myelofibrosis impact outcomes? A pooled analysis of the Comfort I and II studies. American Society of Hematology Annual Meeting and Exposition; December 11-14, 2021. Abstract 1505.