ABSTRACT
Therapy-related acute myeloid leukemia (AML) is a long term complication of chemotherapy for a variety of cancers. In most cases, the marrow demonstrates high risk cytogenetics and the prognosis is poor. In a minority of patients "good risk" cytogenetics, including t(15;17)(q22;q12), are seen and the patient's prognosis is similar to those who have de novo disease. Currently we present a patient who developed therapy-related acute promyelocytic leukemia (APL) after chemoradiotherapy for breast cancer. This case was especially atypical because the leukemic cells were CD34(+), which is an unusual immunophenotype for APL. Recognition that this patient had APL, rather than the more common therapy-related MDS or AML, was imperative to initiate chemotherapy in a timely manner.
ABSTRACT
Crizotinib as the first-generation ALK inhibitor has shown significant activity in ALK-mutated non-small cell lung cancer (NSCLC). Second- and third-generation ALK inhibitors are entering clinical applications for ALK+ NSCLC. In addition, a third-generation ALK inhibitor, lorlatinib (PF-06463922), was reported to resensitize NSCLC to crizotinib. This review provided a summary of clinical development of alectinib, ceritinib, brigatinib (AP26113), and lorlatinib.
Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic use , Receptor Protein-Tyrosine Kinases/antagonists & inhibitors , Aminopyridines , Anaplastic Lymphoma Kinase , Carbazoles/therapeutic use , Carcinoma, Non-Small-Cell Lung/enzymology , Carcinoma, Non-Small-Cell Lung/pathology , Humans , Kaplan-Meier Estimate , Lactams , Lactams, Macrocyclic/therapeutic use , Lung Neoplasms/enzymology , Lung Neoplasms/pathology , Organophosphorus Compounds/therapeutic use , Piperidines/therapeutic use , Pyrazoles , Pyrimidines/therapeutic use , Receptor Protein-Tyrosine Kinases/genetics , Receptor Protein-Tyrosine Kinases/metabolism , Sulfones/therapeutic useABSTRACT
With the advent of new agents targeting CD20, Bruton's tyrosine kinase, and phosphoinositol-3 kinase for chronic lymphoid leukemia (CLL), more treatment options exist than ever before. B-cell lymphoma-2 (BCL-2) plays a major role in cellular apoptosis and is a druggable target. Small molecule inhibitors of BCL-2 are in active clinical studies. ABT-199 (venetoclax, RG7601, GDC-0199) has been granted breakthrough designation by FDA for relapsed or refractory CLL with 17p deletion. In this review, we summarized the latest clinical development of ABT-199/venetoclax and other novel agents targeting the BCL-2 proteins.
