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Despite initial complete remission rates of up to 90%, long-term, disease-free survival remains poor in patients with newly diagnosed acute lymphoblastic leukemia (ALL). Response to salvage chemotherapy is suboptimal; therefore, novel therapeutic agents are being investigated in order to improve outcomes in these patients. Inotuzumab ozogamicin is a CD22-directed antibody-drug conjugate recently approved by the US Food and Drug Administration for the treatment of adults with relapsed or refractory B-cell precursor ALL. Inotuzumab ozogamicin improves response rate, minimal residual disease negativity, and survival compared to standard chemotherapy in this population. In addition, it offers more opportunities to proceed to an allogeneic stem cell transplant in patients who otherwise may not be candidates.

Objective: To evaluate the efficacy and safety of daunorubicin and cytarabine liposome in older adults with newly diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC). Data Source: A literature search of PubMed and MEDLINE (January 2017 to January 2018) was performed using the terms CPX-351, Vyxeos, daunorubicin and cytarabine liposome, and acute myeloid leukemia. Study Selection/Data Extraction: Phase I, II, and III clinical trials evaluating the efficacy and safety of daunorubicin and cytarabine liposome were reviewed with a specific focus on its use in older patients with newly diagnosed AML. All peer-reviewed articles with clinically relevant information were evaluated for inclusion. Data Synthesis: The phase II trial demonstrated that daunorubicin and cytarabine liposome improved response rates (RR), but there was no difference in event-free survival and overall survival in the overall patient population. However, clinical benefit was most pronounced in secondary AML with an increased RR and survival. The phase III trial illustrated that daunorubicin and cytarabine liposome improved survival and RR with tolerable toxicity compared with standard 7 plus 3 (daunorubicin and cytarabine) in patients 60 to 75 years of age with t-AML or AML-MRC. More patients proceeded to a stem cell transplant, and 30-day and 60-day mortality was lower with daunorubicin and cytarabine liposome. Grade 3 to 5 toxicities were similar between the 2 groups, except daunorubicin and cytarabine liposome had prolonged cytopenia and a higher risk of hemorrhage. Conclusions: Daunorubicin and cytarabine liposome improves RR and survival, with tolerable toxicity in older patients with t-AML or AML-MRC.

Acute myeloid leukemia (AML) is a hematologic malignancy that affects predominantly older patients, with a median age of diagnosis around 67. Overall prognosis is poor; however, novel targeted therapies that can potentially improve outcomes in these patients have emerged in recent years. Mutations in isocitrate dehydrogenase (IDH) occur in 20% of AML diagnoses. IDH2 performs a crucial role in cellular metabolism, and when this enzyme is inhibited, the cell cannot rid itself of endogenous products and is thus marked for apoptosis. The US Food and Drug Administration (FDA) approved the first mutant IDH2 inhibitor, enasidenib, for patients with relapsed or refractory IDH2-mutated AML detected by an FDA-approved test.

To evaluate the efficacy and safety of midostaurin in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation in newly diagnosed FLT3-mutated acute myeloid leukemia (AML).A literature search of PubMed and MEDLINE (September 2017) was performed using the terms midostaurin, PKC412, FLT3 gene, and acute myeloid leukemia.Clinical trials evaluating the efficacy and safety of midostaurin in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation were reviewed for the treatment of newly diagnosed FLT3-mutated AML. All peer-reviewed articles with clinically relevant information were evaluated for inclusion.Midostaurin is a multikinase inhibitor also targeting FLT3 indicated for the treatment of newly diagnosed FLT3-mutated AML. A phase III trial illustrated that midostaurin in combination with standard chemotherapy improved event-free survival, disease-free survival, and overall survival in patients with newly diagnosed FLT3-mutation-positive AML compared with standard chemotherapy alone. However, midostaurin did not show a difference in the rate of patients who proceeded to receive an allogeneic stem cell transplant compared with placebo. There was no significant difference in toxicity between the midostaurin and placebo groups, except that more patients experienced grade 3 to 5 anemia and rash with midostaurin.Midostaurin in combination with standard induction and consolidation is safe and efficacious in newly diagnosed FLT3-mutated AML.