Investigating CAR T-Cell Therapy in Lymphoma

Radhakrishnan Ramchandren, MD: This was a study that evaluated a novel Bruton’s tyrosine kinase (BTK) inhibitor in mantle cell lymphoma. This was a phase II study. It was international, and it looked at patients who had received at least 2 lines of prior therapy.

Acalabrutinib is a novel BTK inhibitor that is more selective to the BTK enzyme. Theoretically, it has less off-target effects and is a more potent inhibitor of BTK compared with ibrutinib, based on preclinical work.

This study looked at 142 patients and was a single-arm study. It showed an overall response rate of over 80% and a complete response rate of 40%, which compares favorably to ibrutinib. However, I would caution everyone that this was not a comparative study to ibrutinib. Importantly, in exclusion criteria, any cardiac issues or patients who had received prior BTK or PI3-kinase inhibitors were excluded from the study. So, the data as to whether or not this can be used after ibrutinib are currently unclear.

The overall response rate was 81%, with a high complete response rate of 40%. The side effect profile of acalabrutinib did appear to be slightly different than with ibrutinib. However, there were cytopenias noted—also seen with ibrutinib—as well as AST (aspartate aminotransferase), ALT (alanine aminotransferase) abnormalities.

Given that this is early follow-up and was done in a relatively small population compared with what we see with ibrutinib, at this time, further follow-up is necessary to identify whether this is truly better, in terms of toxicity and efficacy, to ibrutinib. Currently, there are no head-to-head studies comparing the 2. The question also remains as to whether or not these drugs can be used after one or the other in sequence.

I would also venture to say that patients who have relapsed after 2 lines of therapy may benefit from BTK inhibitors. At this time, there is no definitive way to make a decision between acalabrutinib and ibrutinib in this patient population. However, side effect profiles, as well as patient convenience—as acalabrutinib is an intravenous agent and ibrutinib is an oral agent)—must be considered in this setting.

Transcript Edited for Clarity