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The Evolution to BTK Inhibitors in CLL Treatment

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March 19, 2021

This therapy has moved into the frontline setting

  • Acalabrutinib (brand name: Calquence) is now used in frontline management
  • Dr. James Gerson prefers acalabrutinib because it has fewer side effects than ibrutinib in a similar patient population
  • According to results from the ELEVATE-TN trial, progression-free survival doesn’t differ with acalabrutinib alone, compared to in combination with obinutuzumab (brand name: Gazyva)
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Chronic lymphocytic leukemia (CLL) treatment used to be one-size-fits-all. Today, the approach has shifted to more targeted therapies, thanks to the introduction of the Bruton’s tyrosine kinase (BTK) inhibitors.

“We’ve moved far away from chemotherapy in the treatment of CLL in the past couple of years,” Dr. James Gerson, hematologist-oncologist at Penn Medicine, tells SurvivorNet Connect. “The first big move was to ibrutinib [brand name: Imbruvica], the first-in-class BTK inhibitor.”

Since then, acalabrutinib (brand name: Calquence) has also been approved. And while initially its only use was in the relapsed-refractory setting, today it is also available for the frontline management of CLL. As with ibrutinib, patients continue on acalabrutinib until progression or toxicity. “You really are in it for the long haul,” Dr. Gerson says.

He prefers acalabrutinib because it has fewer side effects than ibrutinib in a similar patient population. “Because of that alone, I think it’s a very reasonable choice for patients,” he says.

There has been some question about whether acalabrutinib should be used in combination with an anti-CD20 monoclonal antibody such as obinutuzumab (brand name: Gazyva), as the ELEVATE-TN trial investigated. However, because the progression-free survival curves in the trial did not differ between acalabrutinib alone and acalabrutinib plus obinutuzumab, “I generally just use it as monotherapy,” he says.