Potential breakthroughs with investigational drugs for hairy cell leukemia.
BACKGROUND
Hairy cell leukemia (HCL) is a rare subtype of B-cell chronic lymphoid leukemia. It is characterized by progressive pancytopenia, splenomegaly and infiltrations of the bone marrow, liver and spleen. Over the last few years, several new immunological drugs, particularly immunotoxins, BRAF inhibitors and B-cell receptor (BCR) pathway inhibitors have been developed and investigated as potential treatment options.


METHODS
This article summarizes recent investigational therapies of HCL, looking at their: mechanism of action, pharmacological properties, clinical activity and toxicity, as well as their emerging role in its treatment. The authors conducted a literature review of the MEDLINE database for articles in English concerning immunotoxins, BRAF inhibitors and BCR pathway inhibitors via PubMed. Publications from 2000 through to June 2015 were scrutinized. The search terms used were: BRAF, vemurafenib, dabrafenib, ibrutinib, monoclonal antibodies, immunotoxins, moxetumomab pasudotox, and rituximab in conjunction with HCL. The authors also searched manually the conference proceedings from the previous 5 years of the American Society of Hematology, European Hematology Association, American Society of Clinical Oncology, and ACR/ARHP Annual Scientific Meetings were searched manually. Additional relevant publications were obtained by reviewing the references from the chosen articles.


CONCLUSIONS
The use of vemurafenib and moxetumomab pasudotox is a promising new strategy for the treatment of HCL. Data from ongoing and future clinical trials will aid in better defining the status of new drugs in the treatment of HCL.
a 1 Medical University of Lodz, Copernicus Memorial Hospital, Department of Hematology , 93-510 Lodz, ul. Ciołkowskiego 2, Lodz, Poland +48 426 895 191 ; +48 426 895 192 ; robaktad@csk.umed.lodz.pl.
Tadeusz
T
Robak
a 1 Medical University of Lodz, Copernicus Memorial Hospital, Department of Hematology , 93-510 Lodz, ul. Ciołkowskiego 2, Lodz, Poland +48 426 895 191 ; +48 426 895 192 ; robaktad@csk.umed.lodz.pl.
Anna
A
Wolska
b 2 Medical University of Lodz, Department of Experimental Hematology , 93-510 Lodz, ul. Ciołkowskiego 2, Lodz, Poland.
Pawel
P
Robak
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001427:Bacterial Toxins / Q000494:pharmacology / Q000627:therapeutic use; D015195:Drug Design; D015507:Drugs, Investigational / Q000494:pharmacology / Q000627:therapeutic use; D005098:Exotoxins / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D007943:Leukemia, Hairy Cell / Q000188:drug therapy* / Q000473:pathology; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use; D000077484:Vemurafenib
D000970:Antineoplastic Agents; D001427:Bacterial Toxins; D015507:Drugs, Investigational; D005098:Exotoxins; D007211:Indoles; D013449:Sulfonamides; D000077484:Vemurafenib; C541974:immunotoxin HA22
BRAF; CAT-8015; cladribine; dabrafenib; hairy cell leukemia; hairy cell leukemia variant; ibrutinib; immunotoxins; monoclonal antibodies; moxetumomab pasudotox; pentostatin; rituximxab; vemurafenib