CLL Treatment Advances and Frontline Therapy Insights With Dr. Khan

Commentary
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Cyrus M. Khan, MD, hematologist in the Division of Hematology and Cellular Therapy at West Penn Hospital of Allegheny Health Network, discusses how treatment paradigms for chronic lymphocytic leukemia (CLL) have changed in recent years, particularly regarding frontline therapy options.

Transcription:

0:10 | Over the last 10 years, we have seen significant changes. In the past, for younger, fit patients, we typically chose chemotherapy—most commonly the FCR regimen, a combination of fludarabine, cyclophosphamide, and rituximab [Rituxan]. However, due to its toxicity, we were always looking for alternatives. For older patients, we used bendamustine with rituximab [Rituxan], or for even older patients, single-agent chlorambucil—all chemotherapies but generally less effective than targeted treatments. Any chemotherapy, of course, comes with [adverse] effects and can increase the long-term risk of secondary cancers.

0:51 | Now, we have transitioned to being entirely chemotherapy free. Most of our frontline treatments are nonchemotherapy drugs, with 2 major options. One option is starting with a BTK inhibitor; any of the options I mentioned previously, such as acalabrutinib, ibrutinib, or zanubrutinib [Brukinsa], can be used, although second-generation inhibitors like acalabrutinib [Calquence] and zanubrutinib are often preferred over first-generation ones. These treatments are very effective, but patients do need to continue them for life, as they cannot be stopped until the disease progresses. Acalabrutinib can also be combined with immunotherapy, specifically obinutuzumab [Gazyva], an anti-CD20 antibody similar to rituximab but a newer version. When combined, the [intravenous (IV)] therapy lasts 6 months while the acalabrutinib continues.

1:48 | The other major option is a BCL-2 inhibitor, specifically venetoclax, which we also combine with obinutuzumab. Here, the IV therapy continues for 6 months, and venetoclax is given for only 1 year. This regimen is an effective immunotherapy and targeted treatment combination with a defined treatment duration, so it does not have to be lifelong.

2:10 | There are pros and cons to both of these options, and both are excellent choices. Physicians work closely with patients to determine the best treatment for each [patient]. Additionally, there are ongoing combination trials that investigate using BTK inhibitors with venetoclax, with or without immunotherapy, in time-limited regimens. This approach could shape how frontline treatment evolves in the future.



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