- Email: [email protected]
Central Nervous System Myeloid Sarcoma: Time for a New Approach?
Abstracts Pharmaceuticals, Inc., Palo Alto, United States; 8Hollings Cancer
AML-164
Center, Medical University of South Carolina, Charleston, United States; 9Stanford University School of Medicine, Stanford, United
Central Nervous System Myeloid Sarcoma: Time for a New Approach?
States
Tugce Akcan , Zeyad Kanaan, Adan Rios Division of Oncology at UTHealth McGovern Medical School, Houston, Texas, United States
Abstract: Myeloid sarcoma (MS) is a rare extramedullary manifestation of acute leukemia. While it can involve any anatomic site, occurrence in the central nervous system (CNS) is uncommon and poses a diagnostic and management challenge. Owing to its rarity, therapeutic strategies remain individualized. We report a 44-year-old female with a blast crisis and an altered mental status which incuded a receptive aphasia. A brain magnetic resonance imaging (MRI) revealed a large enhancing mass within the left inferior parietal lobe with surrounding edema and small anterior corpus collosum lesions. The patient underwent early intervention with induction chemotherapy. Following chemotherapy, complete restoration of the patient’s mental status and recovery of aphasia was achieved, corresponding with a dramatic cytoreductive response. Considering the patient’s reponse to chemotherapy and the risk of invasive CNS procedures, biopsy of the brain mass was deferred and the patient was monitored closely with the notion that an ongoing treatment response would signify a CNS myeloid sarcoma. Follow up MR images showed an ongoing positive response and post-remission therapy with an allogeneic stem cell transplantation is planned. Survival outcomes of patients with MS are unfavorable and the optimal approach remains individualized due to a lack of guiding prospective studies to elucidate natural history, prognosis, and optimal treatment strategies for this deadly disease. Continuing reporting of anecdotal experiences in managing similar complex scenarios is essential and remains the only reference for clinicians facing this deadly condition.
AML-169 Overall Survival (OS) by Outpatient versus Inpatient Consolidation in a Phase 3 Study of CPX-351 versus 7+3 in Older Adults with Newly Diagnosed, High-Risk Acute Myeloid Leukemia (AML) 1
2
Context: The CPX-351 dual-drug liposomal encapsulation delivers a synergistic 5:1 molar ratio of cytarabine:daunorubicin preferentially to leukemia cells. CPX-351 demonstrated significantly improved OS versus 7+3 in a phase 3 study in older adults with newly diagnosed, secondary or high-risk AML. Standard-of-care 7+3 includes multiple-day cytarabine continuous infusion; in contrast, CPX-351 is given as a 90-minute infusion on Days 1, 3, and 5 and has the potential for outpatient administration. Objective: This exploratory post hoc analysis of the phase 3 trial assessed the setting of consolidation therapy. Design: Phase 3, randomized, open-label trial. Setting: Multicenter study in the United States and Canada. Patients: Adults aged 60-75 years with newly diagnosed, secondary or high-risk AML. Interventions: Patients were randomized 1:1 to 1-2 induction cycles of CPX-351 or 7+3; patients with complete remission (including with incomplete platelet or neutrophil recovery) could receive up to 2 consolidation cycles (CPX-351: 65 units/m2 [cytarabine 65 mg/m2 + daunorubicin 28.6 mg/m2] on Days 1 and 3; or 7+3: cytarabine 100 mg/ m2/day x 5 days + daunorubicin 60 mg/m2 on Days 1-2). Site of administration was not protocol defined; patients who spent 1 night in the hospital during the treatment phase were classified as inpatients for that treatment phase. Main Outcome Measure: OS. Results: Few patients received induction as outpatient therapy. A total of 49/153 patients in the CPX-351 arm and 32/151 patients in the 7+3 arm received consolidation; a substantial proportion of patients received CPX-351 consolidation as outpatients (consolidation cycle 1: 51%; consolidation cycle 2: 61%). This resulted in a reduced mean % of the consolidation treatment phase spent as an inpatient in the CPX-351 arm (consolidation cycle 1: 47.6%; consolidation cycle 2: 39.1%) compared with the 7+3 arm (93.8%; 100%). Median OS is provided in the Table. Median OS was improved for CPX-351 versus the 7+3 arm irrespective of inpatient/outpatient status during consolidation. The safety profile of CPX-351 was generally comparable to that of 7+3. Conclusion: Some patients may be able to successfully receive CPX-351 consolidation as outpatients, potentially reducing hospitalizations associated with treatment administration. This study was supported by Jazz Pharmaceuticals, Inc. Table Median OS by Inpatient Versus Outpatient Status During Consolidation
3
Jonathan Kolitz , Stephen Strickland, Jorge Cortes, Donna Hogge,4 Jeffrey Lancet,5 Stuart Goldberg,6 Karen Chung,7 Robert Ryan,7 Michael Chiarella,7 Arthur Louie,7 Robert Stuart,8 Bruno Medeiros9
Inpatienta
1
Monter Cancer Center, Northwell Health System, Lake Success,
United States; 2Vanderbilt-Ingram Cancer Center, Nashville, United States; MD Anderson Cancer Center, Houston, United States; 4
Gordon and Leslie Diamond Health Care Centre, Vancouver, Can5
ada; H. Lee Moffitt Cancer Center & Research Institute, Tampa, United States; 6John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, United States; 7Jazz
CPX-351
7+3
CPX-351
7+3
Consolidation 1, n/N (%)
24/49 (49)
30/32 (94)
25/49 (51)
2/32 (6)
Median OS, months
14.72
9.26
25.43
6.87
HR (95% CI)
3
Outpatient
0.55 (0.25-1.21)
Consolidation 2, n/N (%)
9/23 (39)
Median OS, months
NR
HR (95% CI)
0.45 (0.09-2.36)
0.10 (0.01-1.11)
12/12 (100) 14/23 (61) 14.31
0/12 (0) e
26.32 e
Patients spent 1 night in the hospital during the indicated treatment phase.
a
Clinical Lymphoma, Myeloma & Leukemia September 2017
- S287
AML-164
Center, Medical University of South Carolina, Charleston, United States; 9Stanford University School of Medicine, Stanford, United
Central Nervous System Myeloid Sarcoma: Time for a New Approach?
States
Tugce Akcan , Zeyad Kanaan, Adan Rios Division of Oncology at UTHealth McGovern Medical School, Houston, Texas, United States
Abstract: Myeloid sarcoma (MS) is a rare extramedullary manifestation of acute leukemia. While it can involve any anatomic site, occurrence in the central nervous system (CNS) is uncommon and poses a diagnostic and management challenge. Owing to its rarity, therapeutic strategies remain individualized. We report a 44-year-old female with a blast crisis and an altered mental status which incuded a receptive aphasia. A brain magnetic resonance imaging (MRI) revealed a large enhancing mass within the left inferior parietal lobe with surrounding edema and small anterior corpus collosum lesions. The patient underwent early intervention with induction chemotherapy. Following chemotherapy, complete restoration of the patient’s mental status and recovery of aphasia was achieved, corresponding with a dramatic cytoreductive response. Considering the patient’s reponse to chemotherapy and the risk of invasive CNS procedures, biopsy of the brain mass was deferred and the patient was monitored closely with the notion that an ongoing treatment response would signify a CNS myeloid sarcoma. Follow up MR images showed an ongoing positive response and post-remission therapy with an allogeneic stem cell transplantation is planned. Survival outcomes of patients with MS are unfavorable and the optimal approach remains individualized due to a lack of guiding prospective studies to elucidate natural history, prognosis, and optimal treatment strategies for this deadly disease. Continuing reporting of anecdotal experiences in managing similar complex scenarios is essential and remains the only reference for clinicians facing this deadly condition.
AML-169 Overall Survival (OS) by Outpatient versus Inpatient Consolidation in a Phase 3 Study of CPX-351 versus 7+3 in Older Adults with Newly Diagnosed, High-Risk Acute Myeloid Leukemia (AML) 1
2
Context: The CPX-351 dual-drug liposomal encapsulation delivers a synergistic 5:1 molar ratio of cytarabine:daunorubicin preferentially to leukemia cells. CPX-351 demonstrated significantly improved OS versus 7+3 in a phase 3 study in older adults with newly diagnosed, secondary or high-risk AML. Standard-of-care 7+3 includes multiple-day cytarabine continuous infusion; in contrast, CPX-351 is given as a 90-minute infusion on Days 1, 3, and 5 and has the potential for outpatient administration. Objective: This exploratory post hoc analysis of the phase 3 trial assessed the setting of consolidation therapy. Design: Phase 3, randomized, open-label trial. Setting: Multicenter study in the United States and Canada. Patients: Adults aged 60-75 years with newly diagnosed, secondary or high-risk AML. Interventions: Patients were randomized 1:1 to 1-2 induction cycles of CPX-351 or 7+3; patients with complete remission (including with incomplete platelet or neutrophil recovery) could receive up to 2 consolidation cycles (CPX-351: 65 units/m2 [cytarabine 65 mg/m2 + daunorubicin 28.6 mg/m2] on Days 1 and 3; or 7+3: cytarabine 100 mg/ m2/day x 5 days + daunorubicin 60 mg/m2 on Days 1-2). Site of administration was not protocol defined; patients who spent 1 night in the hospital during the treatment phase were classified as inpatients for that treatment phase. Main Outcome Measure: OS. Results: Few patients received induction as outpatient therapy. A total of 49/153 patients in the CPX-351 arm and 32/151 patients in the 7+3 arm received consolidation; a substantial proportion of patients received CPX-351 consolidation as outpatients (consolidation cycle 1: 51%; consolidation cycle 2: 61%). This resulted in a reduced mean % of the consolidation treatment phase spent as an inpatient in the CPX-351 arm (consolidation cycle 1: 47.6%; consolidation cycle 2: 39.1%) compared with the 7+3 arm (93.8%; 100%). Median OS is provided in the Table. Median OS was improved for CPX-351 versus the 7+3 arm irrespective of inpatient/outpatient status during consolidation. The safety profile of CPX-351 was generally comparable to that of 7+3. Conclusion: Some patients may be able to successfully receive CPX-351 consolidation as outpatients, potentially reducing hospitalizations associated with treatment administration. This study was supported by Jazz Pharmaceuticals, Inc. Table Median OS by Inpatient Versus Outpatient Status During Consolidation
3
Jonathan Kolitz , Stephen Strickland, Jorge Cortes, Donna Hogge,4 Jeffrey Lancet,5 Stuart Goldberg,6 Karen Chung,7 Robert Ryan,7 Michael Chiarella,7 Arthur Louie,7 Robert Stuart,8 Bruno Medeiros9
Inpatienta
1
Monter Cancer Center, Northwell Health System, Lake Success,
United States; 2Vanderbilt-Ingram Cancer Center, Nashville, United States; MD Anderson Cancer Center, Houston, United States; 4
Gordon and Leslie Diamond Health Care Centre, Vancouver, Can5
ada; H. Lee Moffitt Cancer Center & Research Institute, Tampa, United States; 6John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, United States; 7Jazz
CPX-351
7+3
CPX-351
7+3
Consolidation 1, n/N (%)
24/49 (49)
30/32 (94)
25/49 (51)
2/32 (6)
Median OS, months
14.72
9.26
25.43
6.87
HR (95% CI)
3
Outpatient
0.55 (0.25-1.21)
Consolidation 2, n/N (%)
9/23 (39)
Median OS, months
NR
HR (95% CI)
0.45 (0.09-2.36)
0.10 (0.01-1.11)
12/12 (100) 14/23 (61) 14.31
0/12 (0) e
26.32 e
Patients spent 1 night in the hospital during the indicated treatment phase.
a
Clinical Lymphoma, Myeloma & Leukemia September 2017
- S287