- Email: [email protected]
P109 Results of phase II clinical study of lenalidomide in Japanese patients with myelodysplastic syndrome (MDS)
5. Therapy 8, 17 and 20 pts, respectively. By completing risk analysis, main causes of death were cancer and cardiovascular in WR, MDS-related and cardiovascular in R and MDS-related in NR. 5 year-cumulative incidence of MDS-related deaths significantly differed between the three groups (11.3% vs. 20.4% vs. 28.9% in WR, R and NR, resp, P = 0.043). Conclusion: Absence or loss of response to ESAs was associated with an increased rate of death from AML. Overall survival of pts who lost response after >12 months was significantly better than that of non-responders and of pts with early relapse, while the 2 last categories had similar outcome.
P109 Results of phase II clinical study of lenalidomide in Japanese patients with myelodysplastic syndrome (MDS) H. Harada1 ° , M. Watanabe2 , K. Suzuki3 , S. Yanagita4 , T. Suzuki5 , Y. Yoshida6 , A. Kimura7 , M. Tsudo2 , M. Takatoku8 , K. Ozawa5 . 1 Department of Hematology, Hiroshima University Hospital, Hiroshima, Japan; 2 Department of Hematology, Osaka Red Cross Hospital, Japan; 3 Department of Hematology, Japanese Red Cross Medical Center, Japan; 4 Department of Hematology, Shizuoka General Hospital, Japan; 5 Division of Hematology, Jichi Medical University, Japan; 6 Hematology Center, Ijinkai Takeda Hospital, Japan; 7 Department of Hematology, Hiroshima University Hospital, Japan; 8 Celgene K.K., Japan *E-mail: [email protected] Lenalidomide has an immunomodulatory agent approved by FDA for the treatment of anemia associated with low and Int-1 IPSS risk Myelodysplastic Syndromes (MDS) with a cytogenetic abnormality of chromosome 5 (del 5q). We conducted a multicenter, single-arm clinical trial to evaluate the safety and efficacy of lenalidomide in Japanese patients with anemia in low- or intermediate-1 risk del 5q MDS. Lenalidomide was administered orally once daily on Days 1 to 21 of each 28-day cycle. The interim analysis was performed after completing the sixth treatment cycle. Eleven patients, 5 with transfusion-dependent anemia and 6 with transfusion-independent symptomatic anemia, received the lenalidomide treatment. All of 5 transfusion-dependent patients, who had been transfused at least 4.5 units for consecutive 56 days, successfully became transfusion independent with lenalidomide treatment. In 6 patients with less than 4.5 transfusion units before the treatment, the median hemoglobin concentration increased from 6.4 g/dL at the baseline to 12.7 g/dL after the treatment, with a median change of 5.3 g/dL from the baseline. Thus, efficacy of lenalidomide was confirmed in all of the 11 patients. Abnormal metaphases were eliminated at the time of the completion of cycle 6 in three of ten patients. Furthermore, two of them achieved complete
S123
cytogenetic remission on day 169 as assessed by the interphase FISH procedure. The pre-existing neutropenia and thrombocytopenia was unaffected by lenalidomide, but was manageable by either dose interruptions or modifications. We conclude that lenalidomide is a highly active drug for Japanese MDS patients with anemic symptoms.
P110 Lenalidomide in low and int-1 risk MDS with del5q: efficacy and quality of life E. Oliva1 ° , R. Latagliata2 , M. Breccia2 , F. Morabito3 , R. Ghio4 , A. Poloni5 , C. Barate6 , A. Cortelezzi7 , A. Ricco8 , C. Alati1 , M. Aloe Spiriti9 , F. Nobile1 . 1 Hematology Unit, Azienda Ospedaliera B-M-M, Reggio Calabria, Italy; 2 Dept of Cellular Biotechnology and Hematology, University La Sapienza, Rome, Italy; 3 Hematology Unit, Azienda Ospedaliera di Cosenza, Italy; 4 Hematology, Ospedale San Martino, Genova, Italy; 5 Hematology, Ospedale di Torrette di Ancona, Italy; 6 Dept of Oncology, Transplant and New Technologies in Medicine, University of Pisa, Italy; 7 Hematology, Ospedale Maggiore, Milan, Italy; 8 Hematology, University of Bari, Italy; 9 Hematology, Azienda Ospedaliera Sant Andrea, Rome, Italy *E-mail: [email protected] Introduction: Lenalidomide induces remissions in MDS patients with del5q. We present preliminary results of a prospective single-arm trial in 49 low and Int-1 IPSS risk MDS patients with del5q treated with lenalidomide to evaluate safety, efficacy, and changes in QoL. Methods: All patients receive lenalidomide at an initial 10 mg daily dose. Dose reduction is prescribed according to adverse events. Responses are evaluated according to Cheson’s criteria (2006). QoL (QOL-E questionnaire) is measured at baseline and weeks 8, 12, 24 and 52. Results: Thirteen patients (74±9 years old) are evaluable at 8 weeks. Six cases had one additional cytogenetic abnormality. IPSS risk was 0 in 8 and 0.5 in 5 cases. At 8 weeks, Hb increased from 8.6±1.0 to 9.9±2.0; 6 patients achieved a Hb response (Hb up to 13 g/dL). Five of 11 transfusiondependent patients became transfusion-free. Physical QoL scores increased from 34±9 to 55±13 (p = 0.01) and social scores changed from 17±29 to 46±38 (p = 0.09). Drug discontinuation followed by dose reduction was required in 10 patients due to significant neutropenia (associated with thrombocytopenia in 3 cases and hospitalization because of infection in 2). One patient refused to continue study drug because of progressive anemia. Conclusions: Though the starting dose was relatively low, initial hematological toxicity did limit lenalidomide dosing so that most patients required an early reduction. Preliminary results confirm that lenalidomide induces erythroid responses and transfusion independence with significant improvements in QoL.
P109 Results of phase II clinical study of lenalidomide in Japanese patients with myelodysplastic syndrome (MDS) H. Harada1 ° , M. Watanabe2 , K. Suzuki3 , S. Yanagita4 , T. Suzuki5 , Y. Yoshida6 , A. Kimura7 , M. Tsudo2 , M. Takatoku8 , K. Ozawa5 . 1 Department of Hematology, Hiroshima University Hospital, Hiroshima, Japan; 2 Department of Hematology, Osaka Red Cross Hospital, Japan; 3 Department of Hematology, Japanese Red Cross Medical Center, Japan; 4 Department of Hematology, Shizuoka General Hospital, Japan; 5 Division of Hematology, Jichi Medical University, Japan; 6 Hematology Center, Ijinkai Takeda Hospital, Japan; 7 Department of Hematology, Hiroshima University Hospital, Japan; 8 Celgene K.K., Japan *E-mail: [email protected] Lenalidomide has an immunomodulatory agent approved by FDA for the treatment of anemia associated with low and Int-1 IPSS risk Myelodysplastic Syndromes (MDS) with a cytogenetic abnormality of chromosome 5 (del 5q). We conducted a multicenter, single-arm clinical trial to evaluate the safety and efficacy of lenalidomide in Japanese patients with anemia in low- or intermediate-1 risk del 5q MDS. Lenalidomide was administered orally once daily on Days 1 to 21 of each 28-day cycle. The interim analysis was performed after completing the sixth treatment cycle. Eleven patients, 5 with transfusion-dependent anemia and 6 with transfusion-independent symptomatic anemia, received the lenalidomide treatment. All of 5 transfusion-dependent patients, who had been transfused at least 4.5 units for consecutive 56 days, successfully became transfusion independent with lenalidomide treatment. In 6 patients with less than 4.5 transfusion units before the treatment, the median hemoglobin concentration increased from 6.4 g/dL at the baseline to 12.7 g/dL after the treatment, with a median change of 5.3 g/dL from the baseline. Thus, efficacy of lenalidomide was confirmed in all of the 11 patients. Abnormal metaphases were eliminated at the time of the completion of cycle 6 in three of ten patients. Furthermore, two of them achieved complete
S123
cytogenetic remission on day 169 as assessed by the interphase FISH procedure. The pre-existing neutropenia and thrombocytopenia was unaffected by lenalidomide, but was manageable by either dose interruptions or modifications. We conclude that lenalidomide is a highly active drug for Japanese MDS patients with anemic symptoms.
P110 Lenalidomide in low and int-1 risk MDS with del5q: efficacy and quality of life E. Oliva1 ° , R. Latagliata2 , M. Breccia2 , F. Morabito3 , R. Ghio4 , A. Poloni5 , C. Barate6 , A. Cortelezzi7 , A. Ricco8 , C. Alati1 , M. Aloe Spiriti9 , F. Nobile1 . 1 Hematology Unit, Azienda Ospedaliera B-M-M, Reggio Calabria, Italy; 2 Dept of Cellular Biotechnology and Hematology, University La Sapienza, Rome, Italy; 3 Hematology Unit, Azienda Ospedaliera di Cosenza, Italy; 4 Hematology, Ospedale San Martino, Genova, Italy; 5 Hematology, Ospedale di Torrette di Ancona, Italy; 6 Dept of Oncology, Transplant and New Technologies in Medicine, University of Pisa, Italy; 7 Hematology, Ospedale Maggiore, Milan, Italy; 8 Hematology, University of Bari, Italy; 9 Hematology, Azienda Ospedaliera Sant Andrea, Rome, Italy *E-mail: [email protected] Introduction: Lenalidomide induces remissions in MDS patients with del5q. We present preliminary results of a prospective single-arm trial in 49 low and Int-1 IPSS risk MDS patients with del5q treated with lenalidomide to evaluate safety, efficacy, and changes in QoL. Methods: All patients receive lenalidomide at an initial 10 mg daily dose. Dose reduction is prescribed according to adverse events. Responses are evaluated according to Cheson’s criteria (2006). QoL (QOL-E questionnaire) is measured at baseline and weeks 8, 12, 24 and 52. Results: Thirteen patients (74±9 years old) are evaluable at 8 weeks. Six cases had one additional cytogenetic abnormality. IPSS risk was 0 in 8 and 0.5 in 5 cases. At 8 weeks, Hb increased from 8.6±1.0 to 9.9±2.0; 6 patients achieved a Hb response (Hb up to 13 g/dL). Five of 11 transfusiondependent patients became transfusion-free. Physical QoL scores increased from 34±9 to 55±13 (p = 0.01) and social scores changed from 17±29 to 46±38 (p = 0.09). Drug discontinuation followed by dose reduction was required in 10 patients due to significant neutropenia (associated with thrombocytopenia in 3 cases and hospitalization because of infection in 2). One patient refused to continue study drug because of progressive anemia. Conclusions: Though the starting dose was relatively low, initial hematological toxicity did limit lenalidomide dosing so that most patients required an early reduction. Preliminary results confirm that lenalidomide induces erythroid responses and transfusion independence with significant improvements in QoL.