Ibrutinib in B-cell Lymphomas.
The standard frontline therapy for diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL) includes the use of chemoimmunotherapy and/or radiation therapy. When patients with these diseases relapse or are refractory to therapy, their diseases are considered incurable outside of the setting of an autologous or allogeneic stem cell transplant, which many patients are not candidates for due to age or comorbidities. The oral Bruton's tyrosine kinase (BTK) inhibitor, ibrutinib, targets the B-cell receptor (BCR) signaling pathway that is critical in the survival of these malignancies. It has shown promising activity in certain subtypes of DLBCL, in relapsed or refractory FL, and in relapsed or refractory MCL for which it has recently received FDA approval and should be considered for use in patients in first relapse. Ibrutinib is an oral therapy taken daily that has been well tolerated by patients. Given the high response rates, tolerability, and acceptable toxicities of ibrutinib therapy, it is now being evaluated in combination therapy both in relapsed B-cell malignancies and frontline studies in DLBCL and MCL. Several other promising agents targeting different kinases in the BCR signaling pathway also are currently under investigation.
Department of Hematology, Arthur G James Comprehensive Cancer Center, The Ohio State University, 320 W 10th Avenue, A350C Starling Loving Hall, Columbus, OH, 43210, USA, kami.maddocks@osumc.edu.
Kami
K
Maddocks
Kristie A
KA
Blum
D000225:Adenine / Q000031:analogs & derivatives; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D006801:Humans; D000077269:Lenalidomide; D016393:Lymphoma, B-Cell / Q000188:drug therapy*; D008224:Lymphoma, Follicular / Q000188:drug therapy*; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy / Q000628:therapy; D010880:Piperidines; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011719:Pyrazines / Q000627:therapeutic use; D011720:Pyrazoles / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D015398:Signal Transduction; D013792:Thalidomide / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001897:Boronic Acids; D010880:Piperidines; D011719:Pyrazines; D011720:Pyrazoles; D011743:Pyrimidines; C551803:ibrutinib; D013792:Thalidomide; D000069286:Bortezomib; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; D000077269:Lenalidomide; D000225:Adenine