Novel precision medicine approaches and treatment strategies in hematological malignancies

Abstract

Genetic testing has been applied for decades in clinical routine diagnostics of hematological malignancies to improve disease (sub)classification, prognostication, patient management, and survival. In recent classifications of hematological malignancies, disease subtypes are defined by key recurrent genetic alterations detected by conventional methods (i.e., cytogenetics, fluorescence in situ hybridization, and targeted sequencing). Hematological malignancies were also one of the first disease areas in which targeted therapies were introduced, the prime example being BCR::ABL1 inhibitors, followed by an increasing number of targeted inhibitors hitting the Achilles’ heel of each disease, resulting in a clear patient benefit. Owing to the technical advances in high‐throughput sequencing, we can now apply broad genomic tests, including comprehensive gene panels or whole‐genome and whole‐transcriptome sequencing, to identify clinically important diagnostic, prognostic, and predictive markers. In this review, we give examples of how precision diagnostics has been implemented to guide treatment selection and improve survival in myeloid (myelodysplastic syndromes and acute myeloid leukemia) and lymphoid malignancies (acute lymphoblastic leukemia, diffuse large B‐cell lymphoma, and chronic lymphocytic leukemia). We discuss the relevance and potential of monitoring measurable residual disease using ultra‐sensitive techniques to assess therapy response and detect early relapses. Finally, we bring up the promising avenue of functional precision medicine, combining ex vivo drug screening with various omics technologies, to provide novel treatment options for patients with advanced disease. Although we are only in the beginning of the field of precision hematology, we foresee rapid development with new types of diagnostics and treatment strategies becoming available to the benefit of our patients.

CRISPR technology in human diseases

“…Chemotherapy, radiotherapy, targeted drug therapy, immunotherapy, and HSCT are the current therapeutic strategies for hematological malignancies. 309 However, each therapy is only effective for some malignant hematological diseases and some patients fail due to relapse and drug resistance, therefore, precision medicine and individualized treatment for patients with hematological malignancies are still the focus of research. 310 …”

Shifting landscape of infectious diseases in hematologic malignancies: A hematopoietic cell transplantation and cellular therapy special edition

“…There has arguably never been a more exciting time to be a clinician or researcher within the field of Oncology/Transplant Infectious Diseases than the present. Progress in the genetic characterization of hematologic malignancies has driven advancements in diagnostic, prognostics, and therapeutics, leading to a rapidly growing repertoire of targeted treatments 1 . Significant developments in hematopoietic cell transplantation (HCT) have increased eligibility for both candidates and donors, leading to more than 80,000 HCTs performed annually worldwide 2,3 .…”