Study Limitations in HLA-Mismatched Microtransplant in Older Patients Newly Diagnosed With Acute Myeloid Leukemia

Purpose This randomized trial evaluated the efficacy and toxicity of sequential gemtuzumab ozogamicin (GO) and standard chemotherapy in older patients with newly diagnosed acute myeloid leukemia (AML). Patients and Methods Patients (n = 472) age 61 to 75 years were randomly assigned to induction chemotherapy with mitoxantrone, cytarabine, and etoposide preceded, or not, by a course of GO (6 mg/m2 on days 1 and 15). In remission, patients received two consolidation courses with or without GO (3 mg/m2 on day 0). The primary end point was overall survival (OS). Results The overall response rate was comparable between the two arms (GO, 45%; no GO, 49%), but induction and 60-day mortality rates were higher in the GO arm (17% v 12% and 22% v 18%, respectively). With median follow-up of 5.2 years, median OS was 7.1 months in the GO arm and 10 months in the no-GO arm (hazard ratio, 1.20; 95% CI, 0.99 to 1.45; P = .07). Other survival end points were similar in both arms. Grade 3 to 4 hematologic and liver toxicities were greater in the GO arm. Treatment with GO provided no benefit in any prognostic subgroup, with the possible exception of patients age < 70 years with secondary AML, but outcomes were significantly worse in the oldest age subgroup because of a higher risk of early mortality. Conclusion As used in this trial, the sequential combination of GO and standard chemotherapy provides no benefit for older patients with AML and is too toxic for those age ≥ 70 years.

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Single-agent and combination biologics in acute myeloid leukemia

Hematology ◽

10.1182/hematology.2019000059 ◽

2019 ◽

Vol 2019 (1) ◽

pp. 548-556 ◽

Cited By ~ 4

Author(s):

Guillaume Richard-Carpentier ◽

Courtney D. DiNardo

Keyword(s):

Acute Myeloid Leukemia ◽

Older Patients ◽

Myeloid Leukemia ◽

Single Agent ◽

Gemtuzumab Ozogamicin ◽

Targeted Agents ◽

Newly Diagnosed ◽

Rational Drug ◽

Genomic Characterization ◽

Acute Myeloid

Abstract Acute myeloid leukemia (AML) is a heterogeneous malignancy characterized by recurrent genetic, epigenetic, and metabolic abnormalities. As a result of our increasing knowledge of the underlying biology of AML leading to rational drug development, several new targeted agents have been recently added to our therapeutic arsenal. The BCL2 inhibitor venetoclax in combination with low-dose cytarabine (LDAC) or hypomethylating agents (HMAs) is safe and effective in older patients with newly diagnosed AML ineligible for intensive chemotherapy. Glasdegib, a hedgehog pathway inhibitor, may be used in combination with LDAC for the same indication and improves survival compared with LDAC alone. In newly diagnosed, fit, older patients with therapy-related AML or AML with myelodysplasia-related changes, the liposome-encapsulated combination of daunorubicin and cytarabine (CPX-351) has shown superiority over the 7 + 3 regimen. The presence of an IDH1 or IDH2 mutation can be effectively targeted by ivosidenib or enasidenib, respectively. Gemtuzumab ozogamicin improves event-free survival in CD33+ patients with favorable or intermediate-risk cytogenetics. With new targeted agents available, comprehensive genomic characterization of AML at diagnosis and relapse is increasingly necessary to select optimal treatment. Herein, we review the new single-agent and combination biologics (omitting FLT3 inhibitors, which are discussed separately) and provide recommendations on how to best use and manage patients on these regimens in clinical practice.

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Phase I trial of plerixafor combined with decitabine in newly diagnosed older patients with acute myeloid leukemia

Haematologica ◽

10.3324/haematol.2017.183418 ◽

2018 ◽

Vol 103 (8) ◽

pp. 1308-1316 ◽

Cited By ~ 14

Author(s):

Gail J. Roboz ◽

Ellen K. Ritchie ◽

Yulia Dault ◽

Linda Lam ◽

Danielle C. Marshall ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Phase I ◽

Older Patients ◽

Myeloid Leukemia ◽

Phase I Trial ◽

Newly Diagnosed ◽

Acute Myeloid

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CPX-351 (cytarabine and daunorubicin) Liposome for Injection Versus Conventional Cytarabine Plus Daunorubicin in Older Patients With Newly Diagnosed Secondary Acute Myeloid Leukemia

Journal of Clinical Oncology ◽

10.1200/jco.2017.77.6112 ◽

2018 ◽

Vol 36 (26) ◽

pp. 2684-2692 ◽

Cited By ~ 248

Author(s):

Jeffrey E. Lancet ◽

Geoffrey L. Uy ◽

Jorge E. Cortes ◽

Laura F. Newell ◽

Tara L. Lin ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Older Patients ◽

Myeloid Leukemia ◽

Bone Marrow Cells ◽

Remission Rate ◽

Phase Iii ◽

Newly Diagnosed ◽

Secondary Acute Myeloid Leukemia ◽

Acute Myeloid

Purpose CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin that delivers a synergistic 5:1 drug ratio into leukemia cells to a greater extent than normal bone marrow cells. Prior clinical studies demonstrated a sustained drug ratio and exposure in vivo and prolonged survival versus standard-of-care cytarabine plus daunorubicin chemotherapy (7+3 regimen) in older patients with newly diagnosed secondary acute myeloid leukemia (sAML). Patients and Methods In this open-label, randomized, phase III trial, 309 patients age 60 to 75 years with newly diagnosed high-risk/sAML received one to two induction cycles of CPX-351 or 7+3 followed by consolidation therapy with a similar regimen. The primary end point was overall survival. Results CPX-351 significantly improved median overall survival versus 7+3 (9.56 v 5.95 months; hazard ratio, 0.69; 95% CI, 0.52 to 0.90; one-sided P = .003). Overall remission rate was also significantly higher with CPX-351 versus 7+3 (47.7% v 33.3%; two-sided P = .016). Improved outcomes were observed across age-groups and AML subtypes. The incidences of nonhematologic adverse events were comparable between arms, despite a longer treatment phase and prolonged time to neutrophil and platelet count recovery with CPX-351. Early mortality rates with CPX-351 and 7+3 were 5.9% and 10.6% (two-sided P = .149) through day 30 and 13.7% and 21.2% (two-sided P = .097) through day 60. Conclusion CPX-351 treatment is associated with significantly longer survival compared with conventional 7+3 in older adults with newly diagnosed sAML. The safety profile of CPX-351 was similar to that of conventional 7+3 therapy.

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Vosaroxin in combination with decitabine in newly diagnosed older patients with acute myeloid leukemia or high-risk myelodysplastic syndrome

Haematologica ◽

10.3324/haematol.2017.168732 ◽

2017 ◽

Vol 102 (10) ◽

pp. 1709-1717 ◽

Cited By ~ 11

Author(s):

Naval Daver ◽

Hagop Kantarjian ◽

Guillermo Garcia-Manero ◽

Elias Jabbour ◽

Gautam Borthakur ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

High Risk ◽

Myelodysplastic Syndrome ◽

Older Patients ◽

Myeloid Leukemia ◽

Newly Diagnosed ◽

Acute Myeloid

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Optimizing Therapy for Acute Myeloid Leukemia

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2008.0076 ◽

2008 ◽

Vol 6 (10) ◽

pp. 1003-1016 ◽

Cited By ~ 8

Author(s):

Holbrook E. Kohrt ◽

Steven E. Coutre

Keyword(s):

Acute Myeloid Leukemia ◽

Older Patients ◽

Myeloid Leukemia ◽

Cytotoxic Chemotherapy ◽

Newly Diagnosed ◽

Younger Patients ◽

The Past ◽

Diagnostic Technologies ◽

Disease Free ◽

Acute Myeloid

The 10-year overall survival for younger patients with newly diagnosed acute myeloid leukemia has improved threefold in the past 2 decades. This improvement has occurred in large part because of advances in supportive care and efforts to optimize standard induction and consolidation therapies applied in a stratified approach based on predictors of individual patient risk. Innovations in diagnostic technologies have broadened the understanding of key prognostic factors, including cytogenetic and molecular status, which define the extensive interpatient heterogeneity of this clonal disease. Despite this progress, only approximately 25% of patients who experience a complete remission with cytotoxic chemotherapy (50%–70% of patients with newly diagnosed disease) remain disease-free. Efforts to develop novel agents are actively ongoing, particularly for older patients (age ≥ 60), and targeted therapies, for specific subsets of patients are being based on a better understanding of the biology of the disease.

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