The Experts below are selected from a list of 237 Experts worldwide ranked by ideXlab platform
Jorge E. Cortes - One of the best experts on this subject based on the ideXlab platform.
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Omacetaxine Mepesuccinate for Chronic Myeloid Leukemia
Expert review of hematology, 2016Co-Authors: Yasmin Rosshandler, Ann Q. Shen, Jorge E. Cortes, Hanna Jean KhouryAbstract:Omacetaxine Mepesuccinate is approved by the Food and Drug Administration in the United States for the treatment of chronic myeloid leukemia in chronic or accelerated phase resistant to two or more tyrosine kinase inhibitors. This review summarizes the mode of action, pharmacokinetics, efficacy and safety of Omacetaxine Mepesuccinate. Omacetaxine Mepesuccinate has activity in chronic myeloid leukemia, especially in the chronic phase, regardless of the presence of ABL1 kinase domain mutations. Omacetaxine Mepesuccinate has distinct but manageable adverse events profile. Omacetaxine Mepesuccinate is a treatment option for a subset of patients with refractory chronic myeloid leukemia.
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incidence and management of myelosuppression in patients with chronic and accelerated phase chronic myeloid leukemia treated with Omacetaxine Mepesuccinate
Leukemia & Lymphoma, 2016Co-Authors: Luke P Akard, Hagop M. Kantarjian, Franck E Nicolini, Meir Wetzler, Jeffrey H Lipton, Michele Baccarani, Jean H Khoury, Sandra E Kurtin, Mihaela Munteanu, Jorge E. CortesAbstract:Omacetaxine Mepesuccinate (Synribo) is an inhibitor of protein synthesis indicated for the treatment of patients with chronic- or accelerated-phase chronic myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors. Myelosuppression is the most common and clinically significant toxicity experienced by patients treated with Omacetaxine. Here, we further examine the patterns of hematologic toxicity observed in clinical trials and describe the approach to management as well as resolution of events. Omacetaxine-related myelosuppression typically occurs more frequently during induction cycles. In general, the myelosuppression observed with Omacetaxine treatment is manageable and reversible, and long-term administration is feasible. Careful monitoring, dose delays and reduction in administration days, and appropriate supportive care are critical for successful management of hematologic toxicity. Concerns regarding myelosuppression, observed with many cancer treatments, should not prevent eligible patients from receiving Omacetaxine, particularly CML patients with unsatisfactory responses to multiple lines of prior treatment.
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final analysis of the efficacy and safety of Omacetaxine Mepesuccinate in patients with chronic or accelerated phase chronic myeloid leukemia results with 24 months of follow up
Cancer, 2015Co-Authors: Jorge E. Cortes, Hagop M. Kantarjian, Luke P Akard, Meir Wetzler, Jeffrey H Lipton, Jean H Khoury, Delphine Rea, Mauricette Michallet, Agnes Guercibresler, Charles ChuahAbstract:BACKGROUND Omacetaxine, a protein synthesis inhibitor, is indicated in the United States for the treatment of patients with chronic-phase (CP) or accelerated-phase (AP) chronic myeloid leukemia (CML) with resistance and/or intolerance to 2 or more tyrosine kinase inhibitors. METHODS The final analysis, with 24 months of follow-up, included additional efficacy and safety analyses to assess the benefit of long-term Omacetaxine administration (1.25 mg/m2 twice daily for 14 days every 28 days followed by 7 days every 28 days) in CP-CML and AP-CML patients receiving >3 cycles. RESULTS Eighteen percent of CP-CML patients achieved a major cytogenetic response (MCyR) with a median duration of 12.5 months (95% confidence interval [CI], 3.5 months to not reached [NR]); responses were maintained for ≥12 months in 3 of 14 responders, and the median overall survival (OS) was 40.3 months (95% CI, 23.8 months to NR). Among patients with AP-CML, 14% achieved or maintained a major hematologic response for a median of 4.7 months (95% CI, 3.6 months to NR); MCyR was not achieved, and the median OS was 14.3 months (95% CI, 6.7-18.7 months). In patients with CP-CML and patients with AP-CML who received >3 cycles of treatment (n = 50 and n = 14, respectively), the median OS was 49.3 months (95% CI, 23.8 months to NR) and 24.6 months (95% CI, 12-37.2 months), respectively. Grade 3 or higher hematologic toxicities were the major side effects (79% and 73% for CP-CML and AP-CML, respectively), with discontinuation due to toxicity in 10% of CP patients and in 5% of AP patients. CONCLUSIONS These results suggest that the long-term administration of Omacetaxine is feasible with dose adjustments to manage toxicities and that Omacetaxine provides a durable benefit for some patients. Cancer 2015;121:1637–1644. © 2015 American Cancer Society.
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Omacetaxine Mepesuccinate in patients with advanced chronic myeloid leukemia with resistance or intolerance to tyrosine kinase inhibitors
Leukemia & Lymphoma, 2015Co-Authors: Jean H Khoury, Jorge E. Cortes, Adam Craig, Meir Wetzler, Michele Baccarani, Annie Claude Benichou, Tamas Masszi, Raghunadharao Digumarti, Luke P AkardAbstract:Omacetaxine Mepesuccinate promotes apoptosis by inhibiting the production of short-lived oncoproteins. The efficacy and safety of Omacetaxine in patients with advanced chronic myeloid leukemia (CML) previously treated with tyrosine kinase inhibitors were assessed in two phase II trials (CML-202 and CML-203). Fifty-one patients in accelerated phase (AP-CML) and 44 in myeloid blast phase (BP-CML) received subcutaneous Omacetaxine 1.25 mg/m(2) twice daily days 1-14 every 28 days until hematologic response/improvement or any cytogenetic response, then days 1-7 every 28 days until disease progression. The primary endpoint was maintenance or attainment of a major hematologic response (MHR). Cytogenetic responses were also evaluated. MHR was 37% in patients with AP-CML and 9% with BP-CML (22% and 5% in those with a history of T315I). Most grade 3/4 adverse events were related to myelosuppression, and were generally manageable. Omacetaxine demonstrates activity and an acceptable safety profile in pretreated patients with advanced CML, irrespective of mutational status.
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effectiveness of homoharringtonine Omacetaxine Mepesuccinate for treatment of acute myeloid leukemia a meta analysis of chinese studies
Clinical Lymphoma Myeloma & Leukemia, 2015Co-Authors: Hagop M. Kantarjian, Susan Obrien, Elias Jabbour, Gisoo Barnes, Ashutosh K Pathak, Jorge E. CortesAbstract:The present meta-analysis provides an overview on the effectiveness of homoharringtonine (HHT) combination regimens to treat acute myeloid leukemia (AML). Because most of these studies were performed in China, Chinese published clinical studies were used for the analysis. A search for studies from 2006 to 2013 of regimens containing HHT for AML treatment was performed using published studies and Chinese databases in Mandarin. The complete response (CR) and overall response (OR) rates were analyzed, and the fixed effects model and random effects model (REM) were calculated. The heterogeneity of the studies was calculated using Q homogeneity statistics. The meta-analysis included 21 studies (n = 1310, n = 229 pediatric, and n = 216 elderly). HHT was given in combination with cytarabine, daunorubicin, idarubicin, aclacinomycin, mitoxantrone, or granulocyte colony-stimulating factor. Heterogeneity was seen in all analyzed pools, but it was most pronounced in retrospective studies. Overall, the REM showed a CR rate of 65.2%. However, in studies in which HHT-containing regimens were compared to regimens without HHT, the CR rates were 69.1% in randomized trials and 62.8% in retrospective studies. Additionally, in studies with exclusively elderly patients, the CR rate was considerably lower than it was for the studies with mixed age populations (47.5% vs. 65.2%). Higher overall CR rates for HHT-containing regimens in AML treatment in the Chinese studies suggest that HHT could be an active agent in the management of AML. Additional clinical trials are warranted to evaluate the efficacy of HHT in AML treatment.
Hagop M. Kantarjian - One of the best experts on this subject based on the ideXlab platform.
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incidence and management of myelosuppression in patients with chronic and accelerated phase chronic myeloid leukemia treated with Omacetaxine Mepesuccinate
Leukemia & Lymphoma, 2016Co-Authors: Luke P Akard, Hagop M. Kantarjian, Franck E Nicolini, Meir Wetzler, Jeffrey H Lipton, Michele Baccarani, Jean H Khoury, Sandra E Kurtin, Mihaela Munteanu, Jorge E. CortesAbstract:Omacetaxine Mepesuccinate (Synribo) is an inhibitor of protein synthesis indicated for the treatment of patients with chronic- or accelerated-phase chronic myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors. Myelosuppression is the most common and clinically significant toxicity experienced by patients treated with Omacetaxine. Here, we further examine the patterns of hematologic toxicity observed in clinical trials and describe the approach to management as well as resolution of events. Omacetaxine-related myelosuppression typically occurs more frequently during induction cycles. In general, the myelosuppression observed with Omacetaxine treatment is manageable and reversible, and long-term administration is feasible. Careful monitoring, dose delays and reduction in administration days, and appropriate supportive care are critical for successful management of hematologic toxicity. Concerns regarding myelosuppression, observed with many cancer treatments, should not prevent eligible patients from receiving Omacetaxine, particularly CML patients with unsatisfactory responses to multiple lines of prior treatment.
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prediction of response and survival in patients with chronic phase chronic myeloid leukemia treated with Omacetaxine Mepesuccinate logistic regression and landmark analyses
Blood Cancer Journal, 2015Co-Authors: Meir Wetzler, Hanna Jean Khoury, Hagop M. Kantarjian, Luke P Akard, Jeffrey H Lipton, Michele Baccarani, Mihaela Munteanu, Franckemmanuel Nicolini, J CortesAbstract:Although many chronic myeloid leukemia (CML) patients initially do well with tyrosine kinase inhibitors (TKIs), some patients develop resistance or intolerance to multiple TKIs and need further therapy. Omacetaxine Mepesuccinate (Omacetaxine), a protein synthesis inhibitor, represents a new class of treatment that can produce major cytogenetic response (MCyR) in patients with CML who have developed resistance or intolerance to TKIs. The US Food and Drug Administration approved subcutaneous Omacetaxine for treatment of CML in chronic-phase (CP) and accelerated-phase patients, with resistance or intolerance to two or more TKIs based on efficacy analysis of a subset of patients from two phase 2, open-label, international, multicenter studies.1, 2 Among the 76 evaluable patients with CML-CP in the efficacy analysis, MCyR was reported in 14 patients (18.4%), including confirmed complete cytogenetic response (CCyR) in six patients (7.9%), with a median MCyR duration of 12.5 months.2, 3 Median progression-free survival (PFS) and overall survival (OS) in CML-CP patients were 9.6 months (95% confidence interval (CI) 6.8–11.3 months) and 40.3 months (95% CI 23.8 months–not reached), respectively.
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final analysis of the efficacy and safety of Omacetaxine Mepesuccinate in patients with chronic or accelerated phase chronic myeloid leukemia results with 24 months of follow up
Cancer, 2015Co-Authors: Jorge E. Cortes, Hagop M. Kantarjian, Luke P Akard, Meir Wetzler, Jeffrey H Lipton, Jean H Khoury, Delphine Rea, Mauricette Michallet, Agnes Guercibresler, Charles ChuahAbstract:BACKGROUND Omacetaxine, a protein synthesis inhibitor, is indicated in the United States for the treatment of patients with chronic-phase (CP) or accelerated-phase (AP) chronic myeloid leukemia (CML) with resistance and/or intolerance to 2 or more tyrosine kinase inhibitors. METHODS The final analysis, with 24 months of follow-up, included additional efficacy and safety analyses to assess the benefit of long-term Omacetaxine administration (1.25 mg/m2 twice daily for 14 days every 28 days followed by 7 days every 28 days) in CP-CML and AP-CML patients receiving >3 cycles. RESULTS Eighteen percent of CP-CML patients achieved a major cytogenetic response (MCyR) with a median duration of 12.5 months (95% confidence interval [CI], 3.5 months to not reached [NR]); responses were maintained for ≥12 months in 3 of 14 responders, and the median overall survival (OS) was 40.3 months (95% CI, 23.8 months to NR). Among patients with AP-CML, 14% achieved or maintained a major hematologic response for a median of 4.7 months (95% CI, 3.6 months to NR); MCyR was not achieved, and the median OS was 14.3 months (95% CI, 6.7-18.7 months). In patients with CP-CML and patients with AP-CML who received >3 cycles of treatment (n = 50 and n = 14, respectively), the median OS was 49.3 months (95% CI, 23.8 months to NR) and 24.6 months (95% CI, 12-37.2 months), respectively. Grade 3 or higher hematologic toxicities were the major side effects (79% and 73% for CP-CML and AP-CML, respectively), with discontinuation due to toxicity in 10% of CP patients and in 5% of AP patients. CONCLUSIONS These results suggest that the long-term administration of Omacetaxine is feasible with dose adjustments to manage toxicities and that Omacetaxine provides a durable benefit for some patients. Cancer 2015;121:1637–1644. © 2015 American Cancer Society.
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effectiveness of homoharringtonine Omacetaxine Mepesuccinate for treatment of acute myeloid leukemia a meta analysis of chinese studies
Clinical Lymphoma Myeloma & Leukemia, 2015Co-Authors: Hagop M. Kantarjian, Susan Obrien, Elias Jabbour, Gisoo Barnes, Ashutosh K Pathak, Jorge E. CortesAbstract:The present meta-analysis provides an overview on the effectiveness of homoharringtonine (HHT) combination regimens to treat acute myeloid leukemia (AML). Because most of these studies were performed in China, Chinese published clinical studies were used for the analysis. A search for studies from 2006 to 2013 of regimens containing HHT for AML treatment was performed using published studies and Chinese databases in Mandarin. The complete response (CR) and overall response (OR) rates were analyzed, and the fixed effects model and random effects model (REM) were calculated. The heterogeneity of the studies was calculated using Q homogeneity statistics. The meta-analysis included 21 studies (n = 1310, n = 229 pediatric, and n = 216 elderly). HHT was given in combination with cytarabine, daunorubicin, idarubicin, aclacinomycin, mitoxantrone, or granulocyte colony-stimulating factor. Heterogeneity was seen in all analyzed pools, but it was most pronounced in retrospective studies. Overall, the REM showed a CR rate of 65.2%. However, in studies in which HHT-containing regimens were compared to regimens without HHT, the CR rates were 69.1% in randomized trials and 62.8% in retrospective studies. Additionally, in studies with exclusively elderly patients, the CR rate was considerably lower than it was for the studies with mixed age populations (47.5% vs. 65.2%). Higher overall CR rates for HHT-containing regimens in AML treatment in the Chinese studies suggest that HHT could be an active agent in the management of AML. Additional clinical trials are warranted to evaluate the efficacy of HHT in AML treatment.
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landmark analysis of overall survival os in patients with chronic cp or accelerated ap phase chronic myeloid leukemia cml treated with Omacetaxine Mepesuccinate
Journal of Clinical Oncology, 2014Co-Authors: Meir Wetzler, Hanna Jean Khoury, Hagop M. Kantarjian, Luke P Akard, Franck E Nicolini, Jeffrey H Lipton, Michele Baccarani, Mihaela C Munteanu, Jorge E. CortesAbstract:7066 Background: Response milestones are used as prognostic indicators in CML. This analysis compared OS in patients with/without response to Omacetaxine. Methods: This was a post hoc landmark anal...
Meir Wetzler - One of the best experts on this subject based on the ideXlab platform.
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incidence and management of myelosuppression in patients with chronic and accelerated phase chronic myeloid leukemia treated with Omacetaxine Mepesuccinate
Leukemia & Lymphoma, 2016Co-Authors: Luke P Akard, Hagop M. Kantarjian, Franck E Nicolini, Meir Wetzler, Jeffrey H Lipton, Michele Baccarani, Jean H Khoury, Sandra E Kurtin, Mihaela Munteanu, Jorge E. CortesAbstract:Omacetaxine Mepesuccinate (Synribo) is an inhibitor of protein synthesis indicated for the treatment of patients with chronic- or accelerated-phase chronic myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors. Myelosuppression is the most common and clinically significant toxicity experienced by patients treated with Omacetaxine. Here, we further examine the patterns of hematologic toxicity observed in clinical trials and describe the approach to management as well as resolution of events. Omacetaxine-related myelosuppression typically occurs more frequently during induction cycles. In general, the myelosuppression observed with Omacetaxine treatment is manageable and reversible, and long-term administration is feasible. Careful monitoring, dose delays and reduction in administration days, and appropriate supportive care are critical for successful management of hematologic toxicity. Concerns regarding myelosuppression, observed with many cancer treatments, should not prevent eligible patients from receiving Omacetaxine, particularly CML patients with unsatisfactory responses to multiple lines of prior treatment.
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prediction of response and survival in patients with chronic phase chronic myeloid leukemia treated with Omacetaxine Mepesuccinate logistic regression and landmark analyses
Blood Cancer Journal, 2015Co-Authors: Meir Wetzler, Hanna Jean Khoury, Hagop M. Kantarjian, Luke P Akard, Jeffrey H Lipton, Michele Baccarani, Mihaela Munteanu, Franckemmanuel Nicolini, J CortesAbstract:Although many chronic myeloid leukemia (CML) patients initially do well with tyrosine kinase inhibitors (TKIs), some patients develop resistance or intolerance to multiple TKIs and need further therapy. Omacetaxine Mepesuccinate (Omacetaxine), a protein synthesis inhibitor, represents a new class of treatment that can produce major cytogenetic response (MCyR) in patients with CML who have developed resistance or intolerance to TKIs. The US Food and Drug Administration approved subcutaneous Omacetaxine for treatment of CML in chronic-phase (CP) and accelerated-phase patients, with resistance or intolerance to two or more TKIs based on efficacy analysis of a subset of patients from two phase 2, open-label, international, multicenter studies.1, 2 Among the 76 evaluable patients with CML-CP in the efficacy analysis, MCyR was reported in 14 patients (18.4%), including confirmed complete cytogenetic response (CCyR) in six patients (7.9%), with a median MCyR duration of 12.5 months.2, 3 Median progression-free survival (PFS) and overall survival (OS) in CML-CP patients were 9.6 months (95% confidence interval (CI) 6.8–11.3 months) and 40.3 months (95% CI 23.8 months–not reached), respectively.
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final analysis of the efficacy and safety of Omacetaxine Mepesuccinate in patients with chronic or accelerated phase chronic myeloid leukemia results with 24 months of follow up
Cancer, 2015Co-Authors: Jorge E. Cortes, Hagop M. Kantarjian, Luke P Akard, Meir Wetzler, Jeffrey H Lipton, Jean H Khoury, Delphine Rea, Mauricette Michallet, Agnes Guercibresler, Charles ChuahAbstract:BACKGROUND Omacetaxine, a protein synthesis inhibitor, is indicated in the United States for the treatment of patients with chronic-phase (CP) or accelerated-phase (AP) chronic myeloid leukemia (CML) with resistance and/or intolerance to 2 or more tyrosine kinase inhibitors. METHODS The final analysis, with 24 months of follow-up, included additional efficacy and safety analyses to assess the benefit of long-term Omacetaxine administration (1.25 mg/m2 twice daily for 14 days every 28 days followed by 7 days every 28 days) in CP-CML and AP-CML patients receiving >3 cycles. RESULTS Eighteen percent of CP-CML patients achieved a major cytogenetic response (MCyR) with a median duration of 12.5 months (95% confidence interval [CI], 3.5 months to not reached [NR]); responses were maintained for ≥12 months in 3 of 14 responders, and the median overall survival (OS) was 40.3 months (95% CI, 23.8 months to NR). Among patients with AP-CML, 14% achieved or maintained a major hematologic response for a median of 4.7 months (95% CI, 3.6 months to NR); MCyR was not achieved, and the median OS was 14.3 months (95% CI, 6.7-18.7 months). In patients with CP-CML and patients with AP-CML who received >3 cycles of treatment (n = 50 and n = 14, respectively), the median OS was 49.3 months (95% CI, 23.8 months to NR) and 24.6 months (95% CI, 12-37.2 months), respectively. Grade 3 or higher hematologic toxicities were the major side effects (79% and 73% for CP-CML and AP-CML, respectively), with discontinuation due to toxicity in 10% of CP patients and in 5% of AP patients. CONCLUSIONS These results suggest that the long-term administration of Omacetaxine is feasible with dose adjustments to manage toxicities and that Omacetaxine provides a durable benefit for some patients. Cancer 2015;121:1637–1644. © 2015 American Cancer Society.
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Omacetaxine Mepesuccinate in patients with advanced chronic myeloid leukemia with resistance or intolerance to tyrosine kinase inhibitors
Leukemia & Lymphoma, 2015Co-Authors: Jean H Khoury, Jorge E. Cortes, Adam Craig, Meir Wetzler, Michele Baccarani, Annie Claude Benichou, Tamas Masszi, Raghunadharao Digumarti, Luke P AkardAbstract:Omacetaxine Mepesuccinate promotes apoptosis by inhibiting the production of short-lived oncoproteins. The efficacy and safety of Omacetaxine in patients with advanced chronic myeloid leukemia (CML) previously treated with tyrosine kinase inhibitors were assessed in two phase II trials (CML-202 and CML-203). Fifty-one patients in accelerated phase (AP-CML) and 44 in myeloid blast phase (BP-CML) received subcutaneous Omacetaxine 1.25 mg/m(2) twice daily days 1-14 every 28 days until hematologic response/improvement or any cytogenetic response, then days 1-7 every 28 days until disease progression. The primary endpoint was maintenance or attainment of a major hematologic response (MHR). Cytogenetic responses were also evaluated. MHR was 37% in patients with AP-CML and 9% with BP-CML (22% and 5% in those with a history of T315I). Most grade 3/4 adverse events were related to myelosuppression, and were generally manageable. Omacetaxine demonstrates activity and an acceptable safety profile in pretreated patients with advanced CML, irrespective of mutational status.
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Omacetaxine Mepesuccinate in chronic myeloid leukemia
Expert Opinion on Pharmacotherapy, 2014Co-Authors: Omar Al Ustwani, Elizabeth A Griffiths, Eunice S Wang, Meir WetzlerAbstract:Introduction: Homoharringtonine (HHT) and other alkaloid esters were originally isolated from the Cephalotaxus evergreen tree and have been used in traditional Chinese medicine since the 1970s to treat a variety of malignancies. Although HHT was investigated for the treatment of chronic myeloid leukemia (CML) in the 1990s with good results, the advent of BCR-ABL1 tyrosine kinase inhibitors (TKIs) at that time rapidly established a new standard of care for CML. Omacetaxine Mepesuccinate is a semisynthetic derivative of HHT with known clinical activity in relapsed or refractory CML following TKI therapy.Areas covered: In this review, we summarize the biologic effects of HHT and its derivative, Omacetaxine, in CML. Additionally, we analyze the concepts learned from the early trials using these drugs. Data from clinical trials resulting in drug approval are also reviewed.Expert opinion: Omacetaxine has a clear role in the CML armamentarium for patients in chronic and accelerated phase who have failed or were ...
Jeffrey H Lipton - One of the best experts on this subject based on the ideXlab platform.
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a safety evaluation of Omacetaxine Mepesuccinate for the treatment of chronic myeloid leukemia
Expert Opinion on Drug Safety, 2016Co-Authors: Moussab Damlaj, Jeffrey H Lipton, Sarit AssoulineAbstract:ABSTRACTIntroduction: Therapy of chronic myeloid leukemia (CML) has been completely transformed by the development of tyrosine kinase inhibitors (TKIs). However, a subset of patients will fail TKI therapy due to resistance or intolerance. Omacetaxine Mepesuccinate (OM), a protein translation inhibitor, is currently the only approved therapy that does not directly target the kinase domain. It has activity for CML patients irrespective of the phase or underlying kinase domain mutation status.Areas covered: We searched the MEDLINE database for articles published in English on homoharringtonine or Omacetaxine from 1970 to present. This article reviews the pharmacokinetics of OM and its clinical evolution for the treatment of CML pre- and post TKI development. Toxicity profile, drug administration and future directions are also discussed.Expert opinion: OM represents a unique addition to the CML therapeutic armamentarium with its distinct mechanism of action and activity. The adverse event profile is manageabl...
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incidence and management of myelosuppression in patients with chronic and accelerated phase chronic myeloid leukemia treated with Omacetaxine Mepesuccinate
Leukemia & Lymphoma, 2016Co-Authors: Luke P Akard, Hagop M. Kantarjian, Franck E Nicolini, Meir Wetzler, Jeffrey H Lipton, Michele Baccarani, Jean H Khoury, Sandra E Kurtin, Mihaela Munteanu, Jorge E. CortesAbstract:Omacetaxine Mepesuccinate (Synribo) is an inhibitor of protein synthesis indicated for the treatment of patients with chronic- or accelerated-phase chronic myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors. Myelosuppression is the most common and clinically significant toxicity experienced by patients treated with Omacetaxine. Here, we further examine the patterns of hematologic toxicity observed in clinical trials and describe the approach to management as well as resolution of events. Omacetaxine-related myelosuppression typically occurs more frequently during induction cycles. In general, the myelosuppression observed with Omacetaxine treatment is manageable and reversible, and long-term administration is feasible. Careful monitoring, dose delays and reduction in administration days, and appropriate supportive care are critical for successful management of hematologic toxicity. Concerns regarding myelosuppression, observed with many cancer treatments, should not prevent eligible patients from receiving Omacetaxine, particularly CML patients with unsatisfactory responses to multiple lines of prior treatment.
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prediction of response and survival in patients with chronic phase chronic myeloid leukemia treated with Omacetaxine Mepesuccinate logistic regression and landmark analyses
Blood Cancer Journal, 2015Co-Authors: Meir Wetzler, Hanna Jean Khoury, Hagop M. Kantarjian, Luke P Akard, Jeffrey H Lipton, Michele Baccarani, Mihaela Munteanu, Franckemmanuel Nicolini, J CortesAbstract:Although many chronic myeloid leukemia (CML) patients initially do well with tyrosine kinase inhibitors (TKIs), some patients develop resistance or intolerance to multiple TKIs and need further therapy. Omacetaxine Mepesuccinate (Omacetaxine), a protein synthesis inhibitor, represents a new class of treatment that can produce major cytogenetic response (MCyR) in patients with CML who have developed resistance or intolerance to TKIs. The US Food and Drug Administration approved subcutaneous Omacetaxine for treatment of CML in chronic-phase (CP) and accelerated-phase patients, with resistance or intolerance to two or more TKIs based on efficacy analysis of a subset of patients from two phase 2, open-label, international, multicenter studies.1, 2 Among the 76 evaluable patients with CML-CP in the efficacy analysis, MCyR was reported in 14 patients (18.4%), including confirmed complete cytogenetic response (CCyR) in six patients (7.9%), with a median MCyR duration of 12.5 months.2, 3 Median progression-free survival (PFS) and overall survival (OS) in CML-CP patients were 9.6 months (95% confidence interval (CI) 6.8–11.3 months) and 40.3 months (95% CI 23.8 months–not reached), respectively.
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final analysis of the efficacy and safety of Omacetaxine Mepesuccinate in patients with chronic or accelerated phase chronic myeloid leukemia results with 24 months of follow up
Cancer, 2015Co-Authors: Jorge E. Cortes, Hagop M. Kantarjian, Luke P Akard, Meir Wetzler, Jeffrey H Lipton, Jean H Khoury, Delphine Rea, Mauricette Michallet, Agnes Guercibresler, Charles ChuahAbstract:BACKGROUND Omacetaxine, a protein synthesis inhibitor, is indicated in the United States for the treatment of patients with chronic-phase (CP) or accelerated-phase (AP) chronic myeloid leukemia (CML) with resistance and/or intolerance to 2 or more tyrosine kinase inhibitors. METHODS The final analysis, with 24 months of follow-up, included additional efficacy and safety analyses to assess the benefit of long-term Omacetaxine administration (1.25 mg/m2 twice daily for 14 days every 28 days followed by 7 days every 28 days) in CP-CML and AP-CML patients receiving >3 cycles. RESULTS Eighteen percent of CP-CML patients achieved a major cytogenetic response (MCyR) with a median duration of 12.5 months (95% confidence interval [CI], 3.5 months to not reached [NR]); responses were maintained for ≥12 months in 3 of 14 responders, and the median overall survival (OS) was 40.3 months (95% CI, 23.8 months to NR). Among patients with AP-CML, 14% achieved or maintained a major hematologic response for a median of 4.7 months (95% CI, 3.6 months to NR); MCyR was not achieved, and the median OS was 14.3 months (95% CI, 6.7-18.7 months). In patients with CP-CML and patients with AP-CML who received >3 cycles of treatment (n = 50 and n = 14, respectively), the median OS was 49.3 months (95% CI, 23.8 months to NR) and 24.6 months (95% CI, 12-37.2 months), respectively. Grade 3 or higher hematologic toxicities were the major side effects (79% and 73% for CP-CML and AP-CML, respectively), with discontinuation due to toxicity in 10% of CP patients and in 5% of AP patients. CONCLUSIONS These results suggest that the long-term administration of Omacetaxine is feasible with dose adjustments to manage toxicities and that Omacetaxine provides a durable benefit for some patients. Cancer 2015;121:1637–1644. © 2015 American Cancer Society.
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landmark analysis of overall survival os in patients with chronic cp or accelerated ap phase chronic myeloid leukemia cml treated with Omacetaxine Mepesuccinate
Journal of Clinical Oncology, 2014Co-Authors: Meir Wetzler, Hanna Jean Khoury, Hagop M. Kantarjian, Luke P Akard, Franck E Nicolini, Jeffrey H Lipton, Michele Baccarani, Mihaela C Munteanu, Jorge E. CortesAbstract:7066 Background: Response milestones are used as prognostic indicators in CML. This analysis compared OS in patients with/without response to Omacetaxine. Methods: This was a post hoc landmark anal...
Luke P Akard - One of the best experts on this subject based on the ideXlab platform.
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incidence and management of myelosuppression in patients with chronic and accelerated phase chronic myeloid leukemia treated with Omacetaxine Mepesuccinate
Leukemia & Lymphoma, 2016Co-Authors: Luke P Akard, Hagop M. Kantarjian, Franck E Nicolini, Meir Wetzler, Jeffrey H Lipton, Michele Baccarani, Jean H Khoury, Sandra E Kurtin, Mihaela Munteanu, Jorge E. CortesAbstract:Omacetaxine Mepesuccinate (Synribo) is an inhibitor of protein synthesis indicated for the treatment of patients with chronic- or accelerated-phase chronic myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors. Myelosuppression is the most common and clinically significant toxicity experienced by patients treated with Omacetaxine. Here, we further examine the patterns of hematologic toxicity observed in clinical trials and describe the approach to management as well as resolution of events. Omacetaxine-related myelosuppression typically occurs more frequently during induction cycles. In general, the myelosuppression observed with Omacetaxine treatment is manageable and reversible, and long-term administration is feasible. Careful monitoring, dose delays and reduction in administration days, and appropriate supportive care are critical for successful management of hematologic toxicity. Concerns regarding myelosuppression, observed with many cancer treatments, should not prevent eligible patients from receiving Omacetaxine, particularly CML patients with unsatisfactory responses to multiple lines of prior treatment.
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prediction of response and survival in patients with chronic phase chronic myeloid leukemia treated with Omacetaxine Mepesuccinate logistic regression and landmark analyses
Blood Cancer Journal, 2015Co-Authors: Meir Wetzler, Hanna Jean Khoury, Hagop M. Kantarjian, Luke P Akard, Jeffrey H Lipton, Michele Baccarani, Mihaela Munteanu, Franckemmanuel Nicolini, J CortesAbstract:Although many chronic myeloid leukemia (CML) patients initially do well with tyrosine kinase inhibitors (TKIs), some patients develop resistance or intolerance to multiple TKIs and need further therapy. Omacetaxine Mepesuccinate (Omacetaxine), a protein synthesis inhibitor, represents a new class of treatment that can produce major cytogenetic response (MCyR) in patients with CML who have developed resistance or intolerance to TKIs. The US Food and Drug Administration approved subcutaneous Omacetaxine for treatment of CML in chronic-phase (CP) and accelerated-phase patients, with resistance or intolerance to two or more TKIs based on efficacy analysis of a subset of patients from two phase 2, open-label, international, multicenter studies.1, 2 Among the 76 evaluable patients with CML-CP in the efficacy analysis, MCyR was reported in 14 patients (18.4%), including confirmed complete cytogenetic response (CCyR) in six patients (7.9%), with a median MCyR duration of 12.5 months.2, 3 Median progression-free survival (PFS) and overall survival (OS) in CML-CP patients were 9.6 months (95% confidence interval (CI) 6.8–11.3 months) and 40.3 months (95% CI 23.8 months–not reached), respectively.
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final analysis of the efficacy and safety of Omacetaxine Mepesuccinate in patients with chronic or accelerated phase chronic myeloid leukemia results with 24 months of follow up
Cancer, 2015Co-Authors: Jorge E. Cortes, Hagop M. Kantarjian, Luke P Akard, Meir Wetzler, Jeffrey H Lipton, Jean H Khoury, Delphine Rea, Mauricette Michallet, Agnes Guercibresler, Charles ChuahAbstract:BACKGROUND Omacetaxine, a protein synthesis inhibitor, is indicated in the United States for the treatment of patients with chronic-phase (CP) or accelerated-phase (AP) chronic myeloid leukemia (CML) with resistance and/or intolerance to 2 or more tyrosine kinase inhibitors. METHODS The final analysis, with 24 months of follow-up, included additional efficacy and safety analyses to assess the benefit of long-term Omacetaxine administration (1.25 mg/m2 twice daily for 14 days every 28 days followed by 7 days every 28 days) in CP-CML and AP-CML patients receiving >3 cycles. RESULTS Eighteen percent of CP-CML patients achieved a major cytogenetic response (MCyR) with a median duration of 12.5 months (95% confidence interval [CI], 3.5 months to not reached [NR]); responses were maintained for ≥12 months in 3 of 14 responders, and the median overall survival (OS) was 40.3 months (95% CI, 23.8 months to NR). Among patients with AP-CML, 14% achieved or maintained a major hematologic response for a median of 4.7 months (95% CI, 3.6 months to NR); MCyR was not achieved, and the median OS was 14.3 months (95% CI, 6.7-18.7 months). In patients with CP-CML and patients with AP-CML who received >3 cycles of treatment (n = 50 and n = 14, respectively), the median OS was 49.3 months (95% CI, 23.8 months to NR) and 24.6 months (95% CI, 12-37.2 months), respectively. Grade 3 or higher hematologic toxicities were the major side effects (79% and 73% for CP-CML and AP-CML, respectively), with discontinuation due to toxicity in 10% of CP patients and in 5% of AP patients. CONCLUSIONS These results suggest that the long-term administration of Omacetaxine is feasible with dose adjustments to manage toxicities and that Omacetaxine provides a durable benefit for some patients. Cancer 2015;121:1637–1644. © 2015 American Cancer Society.
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Omacetaxine Mepesuccinate in patients with advanced chronic myeloid leukemia with resistance or intolerance to tyrosine kinase inhibitors
Leukemia & Lymphoma, 2015Co-Authors: Jean H Khoury, Jorge E. Cortes, Adam Craig, Meir Wetzler, Michele Baccarani, Annie Claude Benichou, Tamas Masszi, Raghunadharao Digumarti, Luke P AkardAbstract:Omacetaxine Mepesuccinate promotes apoptosis by inhibiting the production of short-lived oncoproteins. The efficacy and safety of Omacetaxine in patients with advanced chronic myeloid leukemia (CML) previously treated with tyrosine kinase inhibitors were assessed in two phase II trials (CML-202 and CML-203). Fifty-one patients in accelerated phase (AP-CML) and 44 in myeloid blast phase (BP-CML) received subcutaneous Omacetaxine 1.25 mg/m(2) twice daily days 1-14 every 28 days until hematologic response/improvement or any cytogenetic response, then days 1-7 every 28 days until disease progression. The primary endpoint was maintenance or attainment of a major hematologic response (MHR). Cytogenetic responses were also evaluated. MHR was 37% in patients with AP-CML and 9% with BP-CML (22% and 5% in those with a history of T315I). Most grade 3/4 adverse events were related to myelosuppression, and were generally manageable. Omacetaxine demonstrates activity and an acceptable safety profile in pretreated patients with advanced CML, irrespective of mutational status.
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landmark analysis of overall survival os in patients with chronic cp or accelerated ap phase chronic myeloid leukemia cml treated with Omacetaxine Mepesuccinate
Journal of Clinical Oncology, 2014Co-Authors: Meir Wetzler, Hanna Jean Khoury, Hagop M. Kantarjian, Luke P Akard, Franck E Nicolini, Jeffrey H Lipton, Michele Baccarani, Mihaela C Munteanu, Jorge E. CortesAbstract:7066 Background: Response milestones are used as prognostic indicators in CML. This analysis compared OS in patients with/without response to Omacetaxine. Methods: This was a post hoc landmark anal...
