Contributions
Abstract: S1556
Type: Oral Presentation
Presentation during EHA23: On Sunday, June 17, 2018 from 08:15 - 08:30
Location: Room A4
Background
Patients with high-risk MDS with 5q deletion have a poor prognosis and there is a need for improvement of the current standard azacitidine (AZA) treatment. Lenalidomide (LEN) is an effective treatment for patients with lower-risk MDS with del(5q), and we previously showed that monotherapy with high-dose LEN may have antitumor effects also in high-risk del(5q) myeloid disease. We hypothesized that an upfront combination of AZA and high-dose LEN would be more effective than AZA alone for patients with del(5q) and an approved indication for azacitidine treatment according to the EMA label.
Aims
We designed a Nordic MDS group prospective multicentre randomized phase II trial and evaluated the efficacy and safety of AZA +/- LEN.
Methods
Consecutive patients with high-risk MDS (IPSS INT-2 and high) and AML with multilineage dysplasia and 20-29 % blasts (previous RAEB-t) with a karyotype including del(5q) were included. Patients were randomized to standard dose of AZA 5-2-2 (75 mg/m2/ d sc.) q 4 weeks for 6 cycles, or the same schedule of AZA+LEN. The initial dose of LEN was 10 mg daily 21/28 days. If well tolerated the dose was increased to 25 mg daily during cycle 4-6. The primary end point was response according to international working group (IWG) criteria. Secondary endpoints encompassed safety, AZA cycle interval between groups and survival. Informed consent was obtained.
Results
Seventy-two patients, from 12 centers in Sweden, Denmark, Norway and Finland were included between March 2012 and Jan 2017. Thirty-six patients were randomized to each arm. Median age was 71.5 years (35-84 yrs.). Thirty patients (41%) were female. Fifty-two (75%) patients were diagnosed with MDS and 18 (25%) patients with AML. According to IPSS the cytogenetic risk group was good in 8 patients (11%), intermediate in 4 patients (6%) and poor in 60 patients (83%). Serious adverse events were similar in the two groups. 47 patients (65%) completed 3 cycles and 40 patients (56%) completed the total treatment period. There was no difference in AZA cycle interval between the two groups. In the AZA+LEN arm, 7 out of 36 patients (19%), increased the lenalidomide dose to 25 mg/day during cycle 4-6.
The overall response rate (ORR) was 36% for patients receiving AZA alone and 28% for AZA+LEN (P=0.85) and the corresponding marrow CR rates were 28% and 36%, respectively (P=0.45). At follow-up at 7 months (range, 0 to 36 months) after the last patient completed the trial the median survival was 14 months for patients receiving AZA and 10 months for the AZA+LEN arm (P=0.18). Nine patients (25%) in the AZA arm and eight patients (22%) in the AZA+LEN arm had a hematological improvement (P=0.81).
Cytogenetic response (karyotype showing CR and PR) was achieved in 17% in the AZA arm and 28% in the AZA+LEN arm (P=0.13). Corresponding FISH analysis showed 39% in each group. After 3 cycles there was a trend towards a better cytogenetic response rate (FISH) in the AZA+LEN arm, 50% and 36%, respectively (P=0.052).
Conclusion
This is the first prospective randomized clinical trial in higher-risk MDS with a defined cytogenetic lesion. In this study with high-risk MDS and AML patients with del(5q) and a dismal prognosis the addition of LEN to standard AZA treatment did not improve overall response or survival but may indicate a stronger antitumor response after three cycles.
Session topic: 10. Myelodysplastic syndromes – Clinical
Keyword(s): Acute Myeloid Leukemia, Azacitidine, Immunomodulatory thalidomide analog, Myelodysplasia
Abstract: S1556
Type: Oral Presentation
Presentation during EHA23: On Sunday, June 17, 2018 from 08:15 - 08:30
Location: Room A4
Background
Patients with high-risk MDS with 5q deletion have a poor prognosis and there is a need for improvement of the current standard azacitidine (AZA) treatment. Lenalidomide (LEN) is an effective treatment for patients with lower-risk MDS with del(5q), and we previously showed that monotherapy with high-dose LEN may have antitumor effects also in high-risk del(5q) myeloid disease. We hypothesized that an upfront combination of AZA and high-dose LEN would be more effective than AZA alone for patients with del(5q) and an approved indication for azacitidine treatment according to the EMA label.
Aims
We designed a Nordic MDS group prospective multicentre randomized phase II trial and evaluated the efficacy and safety of AZA +/- LEN.
Methods
Consecutive patients with high-risk MDS (IPSS INT-2 and high) and AML with multilineage dysplasia and 20-29 % blasts (previous RAEB-t) with a karyotype including del(5q) were included. Patients were randomized to standard dose of AZA 5-2-2 (75 mg/m2/ d sc.) q 4 weeks for 6 cycles, or the same schedule of AZA+LEN. The initial dose of LEN was 10 mg daily 21/28 days. If well tolerated the dose was increased to 25 mg daily during cycle 4-6. The primary end point was response according to international working group (IWG) criteria. Secondary endpoints encompassed safety, AZA cycle interval between groups and survival. Informed consent was obtained.
Results
Seventy-two patients, from 12 centers in Sweden, Denmark, Norway and Finland were included between March 2012 and Jan 2017. Thirty-six patients were randomized to each arm. Median age was 71.5 years (35-84 yrs.). Thirty patients (41%) were female. Fifty-two (75%) patients were diagnosed with MDS and 18 (25%) patients with AML. According to IPSS the cytogenetic risk group was good in 8 patients (11%), intermediate in 4 patients (6%) and poor in 60 patients (83%). Serious adverse events were similar in the two groups. 47 patients (65%) completed 3 cycles and 40 patients (56%) completed the total treatment period. There was no difference in AZA cycle interval between the two groups. In the AZA+LEN arm, 7 out of 36 patients (19%), increased the lenalidomide dose to 25 mg/day during cycle 4-6.
The overall response rate (ORR) was 36% for patients receiving AZA alone and 28% for AZA+LEN (P=0.85) and the corresponding marrow CR rates were 28% and 36%, respectively (P=0.45). At follow-up at 7 months (range, 0 to 36 months) after the last patient completed the trial the median survival was 14 months for patients receiving AZA and 10 months for the AZA+LEN arm (P=0.18). Nine patients (25%) in the AZA arm and eight patients (22%) in the AZA+LEN arm had a hematological improvement (P=0.81).
Cytogenetic response (karyotype showing CR and PR) was achieved in 17% in the AZA arm and 28% in the AZA+LEN arm (P=0.13). Corresponding FISH analysis showed 39% in each group. After 3 cycles there was a trend towards a better cytogenetic response rate (FISH) in the AZA+LEN arm, 50% and 36%, respectively (P=0.052).
Conclusion
This is the first prospective randomized clinical trial in higher-risk MDS with a defined cytogenetic lesion. In this study with high-risk MDS and AML patients with del(5q) and a dismal prognosis the addition of LEN to standard AZA treatment did not improve overall response or survival but may indicate a stronger antitumor response after three cycles.
Session topic: 10. Myelodysplastic syndromes – Clinical
Keyword(s): Acute Myeloid Leukemia, Azacitidine, Immunomodulatory thalidomide analog, Myelodysplasia