Investigational treatments for chronic lymphocytic leukemia: a focus on phase 1 and 2 clinical trials

Introduction: During recent years, the introduction of novel drugs, particularly small molecule inhibitors, has led to remarkable progress in both previously untreated and relapsed/refractory (RR) patients in chronic lymphocytic leukemia (CLL). However, further research is necessary to find an optimal cure that responds to the individual needs of the patient. Areas covered: This review discusses new agents in phase 1 and 2 clinical trials currently underway in CLL patients. A literature review of the MEDLINE database for articles in English concerning novel drugs, clinical trials, phase 1, phase 2 and CLL was conducted via PubMed. Publications from 2000 through January 2020 were scrutinized. Conference proceedings from the previous five years of the American Society of Hematology, European Hematology Association and American Society of Clinical Oncology were searched manually. Additional relevant publications were obtained by reviewing the references from the chosen articles. The search also included clinical trials registered in clinicaltrials.gov. Expert opinion: The use of BTK and PI3Kδ inhibitors and BCL-2 antagonist have changed the treatment strategy of CLL. Several clinical trials with novel, unapproved agents are currently ongoing. Their findings should define the role of these novel drugs in the treatment of patients with previously untreated and RR CLL.