Brian T. Hill, MD, PhD, assistant professor, Hematology and Oncology, Cleveland Clinic, discusses combinations for the treatment of patients with mantle cell lymphoma (MCL).

There is a lot of interest in combining Bruton's tyrosine kinase inhibitors with other agents, says Hill, including ibrutinib (Imbruvica) plus venetoclax (Venclexta) and ibrutinib plus ixazomib (Ninlaro). Ixazomib is an oral proteasome inhibitor that has known activity in patients with MCL.

The ongoing phase III PCYC-1143 trial is investigating the combination of ibrutinib and venetoclax in patients with relapsed/refractory MCL. Individually, both agents have achieved response rates of 67% to 75% in this patient population.

Ibrutinib is also being combined with monoclonal antibodies, which Hill says could be an interesting treatment strategy for patients with MCL.

Videos

Brian T. Hill, MD, PhD, assistant professor, Hematology and Oncology, Cleveland Clinic, discusses combinations for the treatment of patients with mantle cell lymphoma.

Dr. Hill Discusses Combinations in MCL

Brian T. Hill, MD, PhD, assistant professor, Hematology and Oncology, Cleveland Clinic, discusses BTK inhibitors in mantle cell lymphoma (MCL).

Acalabrutinib (Calquence) joined ibrutinib (Imbruvica) in late 2017 as the second FDA-approved BTK inhibitor for the treatment of patients with MCL. The approval of acalabrutinib was based on findings from the phase II ACE-LY-004 trial, in which the investigator assessed an objective response rate of 81%.

Hill says that although there are no head-to-head data with acalabrutinib and ibrutinib in MCL, the response rates with acalabrutinib are on par with what are seen with ibrutinib, but the tolerability with acalabrutinib seems to be better.

Additional BTK inhibitors are in development, says Hill, many of which are covalent inhibitors that bind to the same residue as ibrutinib. Some of the non-covalent inhibitors in development may be able to overcome the point mutation in BTK that confers resistance to ibrutinib.

Brian T. Hill, MD, PhD, assistant professor, Hematology and Oncology, Cleveland Clinic, discusses BTK inhibitors in mantle cell lymphoma (MCL).
 

Brian T. Hill, MD, PhD

Articles

Dr. Hill Discusses Combinations in MCL

Dr. Hill Discusses BTK Inhibitors in Mantle Cell Lymphoma