Minerva medica
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Over the last few years, we assisted to an increasing knowledge about acute myeloid leukemia (AML) pathobiology. However, outcomes remain unsatisfactory particularly for adult patients over 60 years old. Not surprisingly several cases of therapy-related AML (tAML) and secondary AML, both characterized by poorer prognosis, are more common in older population. ⋯ Possible future directions include evaluating CPX-351 dose intensification, combining this liposomal formulation with targeted therapies and not least important a better understanding about the mechanism of improved responses in tAML and AML-MRC, two entities recognized to be less chemo-sensitive than other hematologic malignancies. In summary, CPX-351 offers finally something new in the landscape of AML therapy. Herein we will review the rationale behind this new drug product development, the main pharmacological characteristics, and discuss the results of clinical trials that led to its FDA approval at first and by EMA in 2018.
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Review
New monoclonal antibodies and tyrosine kinase inhibitors in B-cell acute lymphoblastic leukemia.
Patients with acute lymphoblastic leukemia (ALL) are characterized by an unfavorable outcome in the majority of adult cases. Several clinical trials have confirmed the usefulness of a pediatric-type therapy applied to adult patients. Adults present with higher risk features at diagnosis that predispose them to chemotherapy resistance and disease relapse after an initial achievement of complete remission. The recent introduction of novel immune-targeted therapies, including monoclonal antibodies (MoAbs) targeting B cell-associated antigens such as CD19 (blinatumumab) and CD22 (inotuzumab), tyrosine kinase inhibitors targeting BCR-ABL1 tyrosine kinase, bispecific antibodies and chimeric antigen receptor T- cell therapy (CAR-T), circumvent B-ALL cell chemo-refractoriness through novel mechanisms of action, potentially eradicating minimal residual disease (MRD) and enabling more patients to receive allogeneic hematopoietic stem cell transplantation and to achieve a better clinical outcome.