Contributions
Abstract: PB2109
Type: Publication Only
Background
In Russia, there are no approved drugs for MDS patients who retain blood transfusion dependence despite the antineoplastic effect observed after hypomethylating therapy. The median survival rates in this cohort are significantly lower than those in the complete response group. The risk of relapse is significantly higher in these patients.
Aims
To assess the possibility of increasing the median survival rate and reducing blood transfusion dependence in patients partially resistant to hypomethylating therapy with azacitidine by administering second-line lenalidomide therapy.
Methods
9 high-risk MDS patients (6 women, 3 men) were enrolled in the study. Cytogenetic analysis of bone marrow revealed no del(5q). The median age was 67 (52 to 84). Before enrollment patients received 4 to 12 cycles of azacitidine at a dose of 75 mg/m2. All patients remained transfusion-dependent. The mean number of blast cells in the bone marrow was 2.8 ± 0.3 % (0.8 ± 0.04 % – 5.2 ± 0.2 %). Lenalidomide was administered at a dose of 10 mg per day for 21 days. In cases when bone marrow relapse had been documented or when no decrease in the degree of blood transfusion dependence was observed for 3 cycles, the drug was discontinued. The average period from diagnosis to beginning lenalidomide therapy was 22 months. The median duration of lenalidomide therapy was 81 days (range: 42 to 168 days). The follow-up period was 18 months.
Results
4 (44 %) patients responded with a decrease in blood transfusion dependence. Three patients had complete response, one demonstrated a 50 % reduction in need for transfusions (intervals between transfusions were increased up to 2 months, dose of packed RBCs reduced from 5–6 to 2–3 per month). All patients responded during the first three cycles of therapy. Five (56 %) patients fully retained a need for blood transfusions. As for side effects, episodes of grade 3 or 4 neutropenia (neutrophil counts below 1,000 in 1 μl) occurred in 50 % of patients during lenalidomide therapy. However, neutropenia was detected during Cycle 1 in one patient among those with a complete response, while in the non-responded group, 4 (80 %) patients had neutropenia during 2–3 cycles of treatment. The treatment was discontinued after cycle 2 in 1 patient due to disease progression into acute leukemia. Four patients stopped taking the drug after cycle 3 due to a lack of effects. Blood transfusion therapy was continued for these patients. Within six months, all four patients underwent disease progression to acute myeloblastic leukemia. The mean duration of the response, characterized by blood transfusion independence, was 8 months. The recurrence of blood transfusion dependence in all patients was accompanied by disease progression, which required third-line therapy with low-dose cytarabine at 15 mg/m2 for 14 days at 21- to 38-day intervals. A partial response was achieved in 5 (55 %) patients. In terms of overall survival, in the general group, 7 (77 %) patients were alive for 12 months. 3 patients (33 %) were alive for 18 months.
Conclusion
Use of lenalidomide in MDS patients with a high risk of progression to acute leukemia with persistent blood transfusion dependence after hypomethylation therapy is clearly justified. The effect observed in the form of cessation/reduction of transfusion dependancy and prolongation of disease-free and overall survival, with satisfactory drug tolerance. This treatment can be recommended in elderly patients with a high comorbidity index when allogeneic stem cell transplantation cannot be performed.
Session topic: 10. Myelodysplastic syndromes – Clinical
Keyword(s): Azacitidine, MDS, Methylation
Abstract: PB2109
Type: Publication Only
Background
In Russia, there are no approved drugs for MDS patients who retain blood transfusion dependence despite the antineoplastic effect observed after hypomethylating therapy. The median survival rates in this cohort are significantly lower than those in the complete response group. The risk of relapse is significantly higher in these patients.
Aims
To assess the possibility of increasing the median survival rate and reducing blood transfusion dependence in patients partially resistant to hypomethylating therapy with azacitidine by administering second-line lenalidomide therapy.
Methods
9 high-risk MDS patients (6 women, 3 men) were enrolled in the study. Cytogenetic analysis of bone marrow revealed no del(5q). The median age was 67 (52 to 84). Before enrollment patients received 4 to 12 cycles of azacitidine at a dose of 75 mg/m2. All patients remained transfusion-dependent. The mean number of blast cells in the bone marrow was 2.8 ± 0.3 % (0.8 ± 0.04 % – 5.2 ± 0.2 %). Lenalidomide was administered at a dose of 10 mg per day for 21 days. In cases when bone marrow relapse had been documented or when no decrease in the degree of blood transfusion dependence was observed for 3 cycles, the drug was discontinued. The average period from diagnosis to beginning lenalidomide therapy was 22 months. The median duration of lenalidomide therapy was 81 days (range: 42 to 168 days). The follow-up period was 18 months.
Results
4 (44 %) patients responded with a decrease in blood transfusion dependence. Three patients had complete response, one demonstrated a 50 % reduction in need for transfusions (intervals between transfusions were increased up to 2 months, dose of packed RBCs reduced from 5–6 to 2–3 per month). All patients responded during the first three cycles of therapy. Five (56 %) patients fully retained a need for blood transfusions. As for side effects, episodes of grade 3 or 4 neutropenia (neutrophil counts below 1,000 in 1 μl) occurred in 50 % of patients during lenalidomide therapy. However, neutropenia was detected during Cycle 1 in one patient among those with a complete response, while in the non-responded group, 4 (80 %) patients had neutropenia during 2–3 cycles of treatment. The treatment was discontinued after cycle 2 in 1 patient due to disease progression into acute leukemia. Four patients stopped taking the drug after cycle 3 due to a lack of effects. Blood transfusion therapy was continued for these patients. Within six months, all four patients underwent disease progression to acute myeloblastic leukemia. The mean duration of the response, characterized by blood transfusion independence, was 8 months. The recurrence of blood transfusion dependence in all patients was accompanied by disease progression, which required third-line therapy with low-dose cytarabine at 15 mg/m2 for 14 days at 21- to 38-day intervals. A partial response was achieved in 5 (55 %) patients. In terms of overall survival, in the general group, 7 (77 %) patients were alive for 12 months. 3 patients (33 %) were alive for 18 months.
Conclusion
Use of lenalidomide in MDS patients with a high risk of progression to acute leukemia with persistent blood transfusion dependence after hypomethylation therapy is clearly justified. The effect observed in the form of cessation/reduction of transfusion dependancy and prolongation of disease-free and overall survival, with satisfactory drug tolerance. This treatment can be recommended in elderly patients with a high comorbidity index when allogeneic stem cell transplantation cannot be performed.
Session topic: 10. Myelodysplastic syndromes – Clinical
Keyword(s): Azacitidine, MDS, Methylation