Side Effects of BGB-16673 Appear Manageable in Early CLL Study

BGB-16673, a first-in-class BTK degrader, is being studied for relapsed or refractory chronic lymphocytic leukemia (CLL) in a phase 1 trial, according to Dr. Lydia Scarfò. Unlike BTK inhibitors that block enzyme activity, this agent leads to the degradation of the BTK protein, which plays a key role in CLL cell growth.

Updated trial findings, which were presented at the 2025 European Hematology Association (EHA) Congress, included more patients and longer follow-up than previously reported. While the study continues to explore the drug’s potential across B-cell malignancies, the safety profile remains a key focus.

So far, side effects have been consistent with expectations for BTK-targeted therapies. The most common issue has been neutropenia, which has generally been manageable with G-CSF support. Atrial fibrillation was reported in two patients — one with a prior history and one during a period of disease progression and infection. There were also two cases of major bleeding as discussed by Scarfò. No new or unexpected safety concerns have been identified to date, and the early data suggest that BGB-16673 is tolerable for most patients.

Scarfò is a physician scientist at the B-cell neoplasia Unit and an assistant professor at Università Vita-Salute San Raffaele, Milano, Italy.

Transcript

Can you explain to patients whether there are any notable safety concerns or side effects reported with this agent, and how they are being managed?

In the phase 1/2 trial, the most important focus is on safety. Based on the observations so far, there have been no unexpected clinical symptoms. The most common or frequent side effect has been neutropenia, which is generally manageable with G-CSF support.

We also observed two cases of atrial fibrillation — one in a patient with a history of atrial fibrillation, and another during a period of disease progression and infection. There were also two major bleeding events, considered relevant due to their severity.

Overall, the safety profile of BGB-16673 appears to be tolerable and manageable, consistent with what we’ve seen from previous agents like covalent BTK inhibitors.

Transcript has been edited for clarity and conciseness.

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