- Email: [email protected]
Efficacy and Safety of CPX-351 versus 7+3 in Older Adults with Newly Diagnosed, Therapy-Related Acute Myeloid Leukemia (tAML): Subgroup Analysis of a Phase 3 Study
Abstracts AML-170 Efficacy and Safety of CPX-351 versus 7+3 in Older Adults with Newly Diagnosed, Therapy-Related Acute Myeloid Leukemia (tAML): Subgroup Analysis of a Phase 3 Study Jeffrey Lancet ,1 David Rizzieri,2 Gary Schiller,3 Robert Stuart,4 Jonathan Kolitz,5 Scott Solomon,6 Laura Newell,7 Harry Erba,8 Geoffrey Uy,9 Robert Ryan,10 Michael Chiarella,10 Arthur Louie,10 Jorge Cortes11 1
H. Lee Moffitt Cancer Center & Research Institute, Tampa, United
States; 2Duke Comprehensive Cancer Center, Durham, United States; 3David Geffen School of Medicine/UCLA, Los Angeles, United 4
States; Hollings Cancer Center, Medical University of South Carolina, Charleston, United States; 5Monter Cancer Center, Northwell Health System, Lake Success, United States; 6BMT Group of Georgia, Atlanta, United States; 7Oregon Health & Science University, Portland,
day mortality (13% vs 25%). Delayed neutrophil and platelet recovery has been observed with CPX-351. Conclusions: CPX-351 was associated with improved outcomes in older patients with untreated tAML. Although this analysis was limited by the small number of patients, outcomes suggest CPX-351 may represent a new therapeutic option for tAML patients. This study was supported by Jazz Pharmaceuticals, Inc.
AML-172 Intensive Chemotherapy vs. Hypomethylating Agents in Older Adults with Newly Diagnosed High-Risk Acute Myeloid Leukemia: A Single Center Experience Pankit Vachhani ,1 Raed Al Yacoub,2 Austin Miller,3 Tara Cronin,1 Evelena Ontiveros,1,4 James Thompson,1,4 Elizabeth Griffiths,1,4 Eunice Wang1,4 1
United States; University of Alabama at Birmingham, Birmingham,
Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, United States; 2Department of Medicine, Jacobs School of Medicine
United States; 9Washington University School of Medicine, St Louis,
and Biomedical Sciences, Buffalo, NY, United States; 3Department of
8
10
United States; Jazz Pharmaceuticals Inc., Palo Alto, United States; 11 MD Anderson Cancer Center, Houston, United States
Biostatistics & Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY, United States; 4Leukemia Service, Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, United States
Context: tAML may occur as a complication of cytotoxic chemotherapy/radiation and is associated with a poor prognosis. CPX-351 is a dual-drug liposomal encapsulation that delivers a synergistic ratio of cytarabine:daunorubicin. In a phase 3 trial in older adults with untreated secondary AML (tAML or with antecedent MDS), CPX-351 significantly improved overall survival (OS) versus 7+3. Objective: This exploratory post hoc analysis of the phase 3 study evaluated outcomes in tAML patients. Design: Phase 3, randomized, open-label trial. Setting: Multicenter study in the United States and Canada. Patients: Adults aged 60-75 years with untreated tAML. Interventions: Patients were randomized 1:1 to induction with 1-2 cycles of CPX-351 (100 units/m2 [cytarabine 100 mg/m2 + daunorubicin 44 mg/m2] on Days 1, 3, and 5 [2nd induction: Days 1 and 3]) or 7+3 (cytarabine 100 mg/m2/day x 7 days [2nd induction: x 5 days] + daunorubicin 60 mg/m2 on Days 1-3 [2nd induction: Days 1-2]). Patients with complete remission (CR) or CR with incomplete platelet or neutrophil recovery (CRi) could receive up to 2 cycles of consolidation therapy. Main Outcome Measure: OS. Results: 304 patients were treated, including 62 (20%) with tAML; baseline characteristics of tAML patients were similar between cohorts, including prior therapy type. tAML patients had typically received prior non-anthracycline chemotherapy alone (25%), radiation alone (25%), or nonanthracycline chemotherapy and radiation (32%). CPX-351 was associated with an OS benefit versus 7+3 in older tAML patients (12.17 vs 6.64 months; HR¼0.49 [95% CI: 0.27-0.88]). Greater proportions of tAML patients treated with CPX-351 versus 7+3 achieved CR+CRi (47% vs 36%) and proceeded to stem cell transplantation (37% vs 27%). The safety profile of CPX-351 in tAML patients was comparable to 7+3, except CPX-351 was associated with lower rates of 30-day mortality (10% vs 16%) and 60-
S288
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Clinical Lymphoma, Myeloma & Leukemia September 2017
Background: High-risk AML (HR-AML), defined as AML with poor cytogenetics, antecedent hematologic disorders, and/or prior myelotoxic therapies, is associated with poor prognosis. Hypomethylating agents (HMA) are often used as an alternative induction regimen in older pts. However it is largely unknown how effective HMA fare against IC in HR-AML. Objectives: To compare results of HMA vs IC in older pts with HR-AML. Methods: Retrospective chart review of patients 60-yrs old with newly diagnosed high-risk AML (defined as prior chemotherapy, prior MDS/MPN, or cytogenetics consistent with AML with myelodysplasia-related changes (AML-MRC)) treated with cytarabine/anthracycline based IC or HMA (azacitidine, decitabine) as upfront therapy at our instittute between 1/2008-12/2016 was conducted. Demographics, hematologic parameters, cytogenetics, comorbidities, treatment response, transplant status, and survival data were compared between treatment groups. Results: 201 pts (98 treated with IC, 103 with HMA) were identified. 35 pts received azacitidine and 68 decitabine. IC-treated pts were younger (mean 68.5 yrs) vs HMA-treated pts (mean 74.9 yrs) with lower incidences of AML-MRC (IC 61 vs. HMA 75) and t-AML (26 vs. 46), but higher rates of antecedent MDS/MPN (IC 47 vs. HMA 32). Comorbidity burden defined by standard scores were similar. HR-AML pts achieved higher CR following IC than HMA (IC 38.8% vs. HMA 27.2%; p¼0.10). Significantly more pts receiving IC subsequently underwent allogeneic stem-cell transplant (alloSCT; 32.7% vs. 4.9%). Adjusting for alloSCT, OS was significantly better with IC than HMA (HR¼0.59, 95% CI: 0.37 to 0.95). No OS advantage favoring IC was seen in pts 65-69 yrs (HR¼0.61, 95% CI: 0.26 to 1.43) or 70-yrs (HR¼0.77, 95% CI: 0.27 to 2.21). OS and CR also did not differ following IC vs
H. Lee Moffitt Cancer Center & Research Institute, Tampa, United
States; 2Duke Comprehensive Cancer Center, Durham, United States; 3David Geffen School of Medicine/UCLA, Los Angeles, United 4
States; Hollings Cancer Center, Medical University of South Carolina, Charleston, United States; 5Monter Cancer Center, Northwell Health System, Lake Success, United States; 6BMT Group of Georgia, Atlanta, United States; 7Oregon Health & Science University, Portland,
day mortality (13% vs 25%). Delayed neutrophil and platelet recovery has been observed with CPX-351. Conclusions: CPX-351 was associated with improved outcomes in older patients with untreated tAML. Although this analysis was limited by the small number of patients, outcomes suggest CPX-351 may represent a new therapeutic option for tAML patients. This study was supported by Jazz Pharmaceuticals, Inc.
AML-172 Intensive Chemotherapy vs. Hypomethylating Agents in Older Adults with Newly Diagnosed High-Risk Acute Myeloid Leukemia: A Single Center Experience Pankit Vachhani ,1 Raed Al Yacoub,2 Austin Miller,3 Tara Cronin,1 Evelena Ontiveros,1,4 James Thompson,1,4 Elizabeth Griffiths,1,4 Eunice Wang1,4 1
United States; University of Alabama at Birmingham, Birmingham,
Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, United States; 2Department of Medicine, Jacobs School of Medicine
United States; 9Washington University School of Medicine, St Louis,
and Biomedical Sciences, Buffalo, NY, United States; 3Department of
8
10
United States; Jazz Pharmaceuticals Inc., Palo Alto, United States; 11 MD Anderson Cancer Center, Houston, United States
Biostatistics & Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY, United States; 4Leukemia Service, Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, United States
Context: tAML may occur as a complication of cytotoxic chemotherapy/radiation and is associated with a poor prognosis. CPX-351 is a dual-drug liposomal encapsulation that delivers a synergistic ratio of cytarabine:daunorubicin. In a phase 3 trial in older adults with untreated secondary AML (tAML or with antecedent MDS), CPX-351 significantly improved overall survival (OS) versus 7+3. Objective: This exploratory post hoc analysis of the phase 3 study evaluated outcomes in tAML patients. Design: Phase 3, randomized, open-label trial. Setting: Multicenter study in the United States and Canada. Patients: Adults aged 60-75 years with untreated tAML. Interventions: Patients were randomized 1:1 to induction with 1-2 cycles of CPX-351 (100 units/m2 [cytarabine 100 mg/m2 + daunorubicin 44 mg/m2] on Days 1, 3, and 5 [2nd induction: Days 1 and 3]) or 7+3 (cytarabine 100 mg/m2/day x 7 days [2nd induction: x 5 days] + daunorubicin 60 mg/m2 on Days 1-3 [2nd induction: Days 1-2]). Patients with complete remission (CR) or CR with incomplete platelet or neutrophil recovery (CRi) could receive up to 2 cycles of consolidation therapy. Main Outcome Measure: OS. Results: 304 patients were treated, including 62 (20%) with tAML; baseline characteristics of tAML patients were similar between cohorts, including prior therapy type. tAML patients had typically received prior non-anthracycline chemotherapy alone (25%), radiation alone (25%), or nonanthracycline chemotherapy and radiation (32%). CPX-351 was associated with an OS benefit versus 7+3 in older tAML patients (12.17 vs 6.64 months; HR¼0.49 [95% CI: 0.27-0.88]). Greater proportions of tAML patients treated with CPX-351 versus 7+3 achieved CR+CRi (47% vs 36%) and proceeded to stem cell transplantation (37% vs 27%). The safety profile of CPX-351 in tAML patients was comparable to 7+3, except CPX-351 was associated with lower rates of 30-day mortality (10% vs 16%) and 60-
S288
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Clinical Lymphoma, Myeloma & Leukemia September 2017
Background: High-risk AML (HR-AML), defined as AML with poor cytogenetics, antecedent hematologic disorders, and/or prior myelotoxic therapies, is associated with poor prognosis. Hypomethylating agents (HMA) are often used as an alternative induction regimen in older pts. However it is largely unknown how effective HMA fare against IC in HR-AML. Objectives: To compare results of HMA vs IC in older pts with HR-AML. Methods: Retrospective chart review of patients 60-yrs old with newly diagnosed high-risk AML (defined as prior chemotherapy, prior MDS/MPN, or cytogenetics consistent with AML with myelodysplasia-related changes (AML-MRC)) treated with cytarabine/anthracycline based IC or HMA (azacitidine, decitabine) as upfront therapy at our instittute between 1/2008-12/2016 was conducted. Demographics, hematologic parameters, cytogenetics, comorbidities, treatment response, transplant status, and survival data were compared between treatment groups. Results: 201 pts (98 treated with IC, 103 with HMA) were identified. 35 pts received azacitidine and 68 decitabine. IC-treated pts were younger (mean 68.5 yrs) vs HMA-treated pts (mean 74.9 yrs) with lower incidences of AML-MRC (IC 61 vs. HMA 75) and t-AML (26 vs. 46), but higher rates of antecedent MDS/MPN (IC 47 vs. HMA 32). Comorbidity burden defined by standard scores were similar. HR-AML pts achieved higher CR following IC than HMA (IC 38.8% vs. HMA 27.2%; p¼0.10). Significantly more pts receiving IC subsequently underwent allogeneic stem-cell transplant (alloSCT; 32.7% vs. 4.9%). Adjusting for alloSCT, OS was significantly better with IC than HMA (HR¼0.59, 95% CI: 0.37 to 0.95). No OS advantage favoring IC was seen in pts 65-69 yrs (HR¼0.61, 95% CI: 0.26 to 1.43) or 70-yrs (HR¼0.77, 95% CI: 0.27 to 2.21). OS and CR also did not differ following IC vs