Portell on the Changing Landscape of Mantle Cell Lymphoma

Craig A. Portell, MD, associate professor of medicine at University of Virginia, discusses the current standard of care for patients with relapsed/refractory mantle cell lymphoma and how sequencing therapies changed the landscape of mantle cell lymphoma (MCL) treatment.

Several Bruton's tyrosine kinase (BTK) inhibitors have been approved for the treatment of mantle cell lymphoma (MCL). The main ones include:

• Ibrutinib (Imbruvica) – This was the first BTK inhibitor approved for MCL by the FDA in 2013. It is used as a treatment for both newly diagnosed and relapsed/refractory MCL.
• Acalbrutinib (Calquence) – Approved in 2017, acalabrutinib is a second-generation BTK inhibitor. It was developed to be more selective for BTK and has a potentially better adverse-effect profile compared with ibrutinib.
• Zanubrutinib (Brukinsa) – Approved in 2019, zanubrutinib is another second-generation BTK inhibitor. It is designed to offer greater potency and selectivity for BTK, with potentially fewer off-target effects than ibrutinib.

Portell highlights that covalent BTK inhibitors are the current standard of care for patients who have not received them as part of first-line therapy. However, as more patients relapse after initial BTK inhibitor treatment, managing their care becomes challenging, especially with the growing complexity of BTK inhibitor resistance.

Chimeric antigen receptor (CAR) T-cell therapy has been beneficial in these cases, and emerging therapies like bispecific antibodies, covalent BTK inhibitors, and venetoclax (Venclexta) offer hope. The sequencing of these treatments depends on individual patient factors.

Transcription:

0:09 | As we are seeing more and more relapsed disease after first-line covalent BTK inhibitors, it is often probably a CAR T-cell therapy, but most patients will have not seen a covalent BTK inhibitor in the first-line relapsed setting. I think covalent BTK inhibitors are the standard of care for that patient population.

0:36 | It has become more complicated as we have learned more about BTK inhibitor resistance, it is hard to know what to do afterwards. The CAR T-cell space has been helpful, [and] we are hopeful to see some interesting data with bispecific antibodies and other new therapies, including covalent BTK inhibitors and venetoclax. These are all therapies that can be hard to know how to sequence, and sometimes it [really depends on the individual] patient.