Promising therapies for the treatment of chronic lymphocytic leukemia.
BACKGROUND
The combination schedule of fludarabine, cyclophosphamide and rituximab is the gold standard of therapy for younger, physically fit chronic lymphocytic leukemia (CLL) patients; it allows achieving high and durable complete response rates. Although treatment outcome has considerably improved with chemo-immunotherapy, most patients eventually relapse and CLL is still incurable. Thus, newer and more rationally developed drugs are needed to improve CLL therapy, particularly in cases of relapsed/refractory disease.


METHODS
The authors review preclinical and clinical data regarding newer CLL agents, currently undergoing examination, such as: signal transduction and cyclin-dependent kinase inhibitors, immunomodulatory agents, B-cell lymphoma 2 inhibitors, next generation mAbs, heat shock protein 90 and histone deacetylase inhibitors, and chimeric antigen receptor T-cell therapy.


CONCLUSIONS
Newer compounds with different mechanisms of action, such as B-cell receptor signal transduction inhibitors, lenalidomide, next generation mAbs and several pro-apoptotic molecules, have shown efficacy in relapsed or refractory CLL patients. Several studies are under way to investigate the efficacy of combinations of these novel drugs. Hopefully, the combined use of these molecules in risk-adapted treatment strategies will change the therapeutic approach in the near future and will pave the way for a long-term control of CLL.
Azienda Ospedaliera di Cosenza, Dipartimento Oncoematologico, Unità Operativa Complessa di Ematologia , Viale della Repubblica, Cosenza 87100 , Italy +39 0984 681329 ; +39 0984 681866 ; fortunato_morabito@tin.it ; massim.gentile@tiscali.it.
Fortunato
F
Morabito
Anna Grazia
AG
Recchia
Ernesto
E
Vigna
Laura
L
De Stefano
Sabrina
S
Bossio
Lucio
L
Morabito
Mariavaleria
M
Pellicanò
Angela
A
Palummo
Francesca
F
Storino
Nadia
N
Caruso
Massimo
M
Gentile
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015195:Drug Design; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D012008:Recurrence; D016896:Treatment Outcome
D000970:Antineoplastic Agents
B-cell lymphoma-2 inhibitors; B-cell receptor signal transduction inhibitors; chronic lymphocytic leukemia; lenalidomide; mAbs; pro-apoptotic molecules