Contributions
Abstract: PB1705
Type: Publication Only
Session title: Myeloproliferative neoplasms - Clinical
Background
Data regarding ruxolitinib safety and efficacy in intermediate-1 risk patients are scarce.
Aims
In this retrospective study, we aimed to document a real-life clinical experience with ruxolitinib in predominantly intermediate risk primary and secondary MF patients.
Methods
Fifty six patients who received ruxolitinib were included into the analyses. All patients were at least 18 years of age and they had INT-1/2 or high risk disease according to DIPSS-plus risk classification.
Results
Patients
The median age of patients was 58 (23-80) years. Overall, 50.9% of patients were male and 49.2 % had PMF. Patient assignment according to DIPSS-plus risk categories goes as follows: 33 patients (57.9 %) in INT-1, 23 patients (40.4 %) in INT-2, 1 patients (1.8%) in high-risk. Hydroxyurea was used previously by 91.2% of the patients before ruxolitinib. JAK2 was obtained positive in 71.9% of the patients.
Efficacy
Overall, a spleen size reduction of at least 35% (spleen response) was achieved in 56.6% of patients (30/53) at any time. A spleen response at 6 months was observed in 41.5 % of patients. Only 36.6 % (11/30) of the patients in INT-1 myelofibrosis group achieved a spleen response at 6 months.
Twenty three patients had MPN-SAF TSS during the course of the treatment. Five patients (21.7%) had at least 50% reductions in myelofibrosis associated symptoms. In 10 patients (43.5%), a 20-50% reduction in symptom score was observed. Four patients (17.4%) had only mild (5-10%) symptom responses.
Safety
Median duration of exposure to ruxolitinib was 22 months (range: 1-80 months). Forty-two patients (%73.7) were still receiving ruxolitinib. Initial dose of ruxolitinib was 20 mg bid in 67% of the patients.
Fifty two out of 57 (91%) experienced any kind of hematologic side effect. Most common hematologic adverse events were anemia (all grades, 84.2%; grade 3-4, 42.1%) and thrombocytopenia (all grades, 38.6%; grade 3-4, 17.5%). Cytopenias were more prominent within the first three months.
A total of 27 out of 57 patients experienced non-hematologic side effects, which were generally grade 1-2. Most common non-hematologic adverse events were fatigue, pneumonia, and elevated liver enzymes. Pulmonary embolism was observed in two patients who had pneumonia. Herpes zoster infection, hepatitis B virus (HBV) reactivation, and urinary tract infection were noted. Overall, three patients diagnosed with cancer including pancreas adenocarcinoma, squamous cell carcinoma of the skin and metastatic neuroendocrine tumor. Patients with INT-1 risk had the similar safety profile.
Survival
A total of 17 (29.8%) deaths occurred during a median follow-up of 22 months. Causes of death were as follows: transformation to acute myeloid leukemia (n=5), disease progression (n=11), and pancreas adenocarcinoma (n=1). In all cohort, overall survival probability at 24 months was 75.1% (95% CI: 59.8% to 85.3%). Median overall survival was not reached.
Since previous studies claim that basal hemoglobin levels lower than 10 g / dL was associated with worse survival outcomes, we stratified survival probabilities according to basal hemoglobin levels as well. Median survival was not reached in both group with Hb< 10 g / dL and Hb ≥ 10 g / dL during the first 2 years, patients with a Hb ≥ 10 g / dL seem to have a better survival. Two year survival probabilities were 58.5 % (95% CI: 34.5 to 76.4%) versus 87.5 % (95% CI: 65.5% to 95.9%), respectively. However, survival curves merged at month 33 and beyond (p=0.15).
Conclusion
Ruxolitinib is safe and effective in all risk groups of patients with myelofibrosis.
Keyword(s): Myelofibrosis, Ruxolitinib
Abstract: PB1705
Type: Publication Only
Session title: Myeloproliferative neoplasms - Clinical
Background
Data regarding ruxolitinib safety and efficacy in intermediate-1 risk patients are scarce.
Aims
In this retrospective study, we aimed to document a real-life clinical experience with ruxolitinib in predominantly intermediate risk primary and secondary MF patients.
Methods
Fifty six patients who received ruxolitinib were included into the analyses. All patients were at least 18 years of age and they had INT-1/2 or high risk disease according to DIPSS-plus risk classification.
Results
Patients
The median age of patients was 58 (23-80) years. Overall, 50.9% of patients were male and 49.2 % had PMF. Patient assignment according to DIPSS-plus risk categories goes as follows: 33 patients (57.9 %) in INT-1, 23 patients (40.4 %) in INT-2, 1 patients (1.8%) in high-risk. Hydroxyurea was used previously by 91.2% of the patients before ruxolitinib. JAK2 was obtained positive in 71.9% of the patients.
Efficacy
Overall, a spleen size reduction of at least 35% (spleen response) was achieved in 56.6% of patients (30/53) at any time. A spleen response at 6 months was observed in 41.5 % of patients. Only 36.6 % (11/30) of the patients in INT-1 myelofibrosis group achieved a spleen response at 6 months.
Twenty three patients had MPN-SAF TSS during the course of the treatment. Five patients (21.7%) had at least 50% reductions in myelofibrosis associated symptoms. In 10 patients (43.5%), a 20-50% reduction in symptom score was observed. Four patients (17.4%) had only mild (5-10%) symptom responses.
Safety
Median duration of exposure to ruxolitinib was 22 months (range: 1-80 months). Forty-two patients (%73.7) were still receiving ruxolitinib. Initial dose of ruxolitinib was 20 mg bid in 67% of the patients.
Fifty two out of 57 (91%) experienced any kind of hematologic side effect. Most common hematologic adverse events were anemia (all grades, 84.2%; grade 3-4, 42.1%) and thrombocytopenia (all grades, 38.6%; grade 3-4, 17.5%). Cytopenias were more prominent within the first three months.
A total of 27 out of 57 patients experienced non-hematologic side effects, which were generally grade 1-2. Most common non-hematologic adverse events were fatigue, pneumonia, and elevated liver enzymes. Pulmonary embolism was observed in two patients who had pneumonia. Herpes zoster infection, hepatitis B virus (HBV) reactivation, and urinary tract infection were noted. Overall, three patients diagnosed with cancer including pancreas adenocarcinoma, squamous cell carcinoma of the skin and metastatic neuroendocrine tumor. Patients with INT-1 risk had the similar safety profile.
Survival
A total of 17 (29.8%) deaths occurred during a median follow-up of 22 months. Causes of death were as follows: transformation to acute myeloid leukemia (n=5), disease progression (n=11), and pancreas adenocarcinoma (n=1). In all cohort, overall survival probability at 24 months was 75.1% (95% CI: 59.8% to 85.3%). Median overall survival was not reached.
Since previous studies claim that basal hemoglobin levels lower than 10 g / dL was associated with worse survival outcomes, we stratified survival probabilities according to basal hemoglobin levels as well. Median survival was not reached in both group with Hb< 10 g / dL and Hb ≥ 10 g / dL during the first 2 years, patients with a Hb ≥ 10 g / dL seem to have a better survival. Two year survival probabilities were 58.5 % (95% CI: 34.5 to 76.4%) versus 87.5 % (95% CI: 65.5% to 95.9%), respectively. However, survival curves merged at month 33 and beyond (p=0.15).
Conclusion
Ruxolitinib is safe and effective in all risk groups of patients with myelofibrosis.
Keyword(s): Myelofibrosis, Ruxolitinib