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December 20, 2019
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VIDEO: More data needed on adding monoclonal antibodies to Bruton tyrosine kinase inhibitors in CLL

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ORLANDO — In this video at ASH Annual Meeting and Exposition, Ryan W. Jacobs, MD, discusses the implications of the ELEVATE-TN trial, which showed acalabrutinib alone or in combination with obinutuzumab extended PFS compared with obinutuzumab and chlorambucil among patients with treatment-naive chronic lymphocytic leukemia.

“All of us who are familiar with using ibrutinib [Imbruvica; Pharmacyclics, Janssen] and its great efficacy were not surprised that acalabrutinib, which is also a BTK [Bruton tyrosine kinase] inhibitor, beat obinutuzumab and chlorambucil,” Jacobs, principal investigator of clinical trials for CLL at Atrium Health’s Levine Cancer Institute, told Healio.

However, the study is significant in that it supported the recent approval of acalabrutinib (Calquence, AstraZeneca) in this setting, he added.

Looking more closely at the data, Jacobs said that adding obinutuzumab (Gazyva, Genentech) to acalabrutinib appeared to improve PFS, although the study was not powered enough to demonstrate an association.

“I do not think this data is actionable at this time in the clinic. I think you just have to use your best clinical judgement ... but it was an interesting finding in the study,” he said. “For perspective, adding rituximab to ibrutinib has not shown any clear benefits, so the question of whether a monoclonal is additive to a BTK inhibitor has not really been felt to be adequately answered.”

The challenge in the current treatment landscape of CLL is determining which of the several available treatment options should be used and when, according to Jacobs.

“This leads to a longer discussion in terms of treatment options with the patients, but in the end, hopefully we can personalize our decisions at this point and make the best treatment decisions for the patient,” Jacobs said. “I think on the horizon, we will ultimately be moving toward combinations of novel agents like BTK and BCL2 inhibition, but that is for the future.”

Reference:

Sharman JP, et al. Abstract 31. Presented at: ASH Annual Meeting and Exposition; Dec. 7-10, 2019; Orlando.

Disclosure: Jacobs reports a consultant role with AbbVie, Gilead, Juno Therapeutics and Verastem; speakers bureau fees from AbbVie, AstraZeneca, Genentech, Janssen, Pharmacyclics LLC and Sanofi; honoraria from TG Therapeutics; and research funding from Pharmacyclics LLC and TG Therapeutics.