Nicole Lamanna, MD, is a hematologic oncologist at the Herbert Irving Comprehensive Cancer Center at NewYork-Presbyterian/Columbia University Irving Medical Center

Catherine C. Coombs, MD, is a hematologist-oncologist and associate clinical professor in the Department of Medicine of the Division of Hematology/Oncology at University of California Irvine Health.

 entitled, “Recent Advances in the Treatment of Chronic Lymphocytic Leukemia.”

I’m Dr William Wierda, professor of medicine in the Department of Leukemia and section head for chronic lymphocytic leukemia [CLL] at The University of Texas MD Anderson Cancer Center in Houston, Texas.

I’m joined today by a panel of experts in CLL and I would like to welcome them and invite each of them to introduce themselves. We’ll start with Jackie Barrientos.

Hi, my name is Jacqueline Barrientos, and I am professor of medicine at the Zucker School of Medicine at Hofstra/Northwell [New Hyde Park, New York]. I do work at the CLL Research and Treatment Program in Long Island, New York.

Hi there, I’m Callie Coombs. I’m at the University of North Carolina [Chapel Hill, North Carolina], where I work as an assistant professor of medicine within the Department of Hematology mostly caring for patients with CLL.

Hi, my name is Nicole Lamanna. I’m at Columbia Universality Medical Center [New York, New York] on the Leukemia Service and director of the CLL Program here.

Hi everybody, Anthony Mato from Memorial Sloan Kettering Cancer Center [New York, New York], director of the CLL Program and very happy to be here today.

Hi, I’m Debbie Stephens. I’m at the Huntsman Cancer Institute at the University of Utah [Salt Lake City, Utah], and I direct the CLL Program here.

: Great. Welcome everybody and thank you for joining me today. We’re going to discuss a number of recent updates in the treatment of CLL that were presented at conferences over 2021, particularly focusing on the ASH [American Society of Hematology meeting] 2021 updates. We’ll discuss the data in the context of standards of care and guidelines for treatment and how these updates impact on our management of our patients with CLL.

We’ll start with targeted therapy, which began with [the] Bruton tyrosine kinase [BTK] inhibitor, ibrutinib [Imbruvica®], which has been available for several years now. We’ve learned over the years that CLL cells are dependent on the kinase activity of Bruton tyrosine kinase for survival, and ibrutinib was the first small molecule inhibitor that was developed, first in the laboratory and then clinically in treatment of patients with CLL. This is an irreversible inhibitor, meaning that it binds covalently to BTK at the cysteine 481 moiety and in doing so it blocks the ATP [adenosine-triphosphate]-binding pocket and inactivates BTK irreversibly. And the only way to replace functional BTK would be resynthesis.

Videos

The rationale for using Bruton tyrosine kinase inhibitors, such as the first-generation option, ibrutinib, as first-line treatment for chronic lymphocytic leukemia.

BTK Inhibitors as Frontline Therapy for CLL

Nicole Lamanna, MD, associate professor of medicine, Hematologic Malignancies Section, Division of Hematology/Oncology, NewYork-Presbyterian/Columbia University Medical Center, discusses the MURANO trial, which evaluated the use of venetoclax and rituximab (Rituxan) combination therapy versus bendamustine and rituximab in patients with chronic lymphocytic leukemia (CLL).

This was the follow-up trial to initial phase I data that supported the tolerability and efficacy of the combination. The next step, according to Lamanna, was to compare the venetoclax combination regimen with the standard of care, a chemoimmunotherapy combination comprised of bendamustine and rituximab.

Three-year follow-up data on the feasibility of fixed-duration venetoclax were presented at the 2018 ASH Annual Meeting. Emerging novel agents such as BTK inhibitors are currently being used indefinitely in patients with CLL, and so the rationale for the follow-up analysis was to determine if therapy could be limited without hindering effectiveness of the treatment.

Nicole Lamanna, MD, associate professor of medicine, Hematologic Malignancies Section, Division of Hematology/Oncology, NewYork-Presbyterian/Columbia University Medical Center, discusses the MURANO trial in patients with chronic lymphocytic leukemia.

Dr. Lamanna Discusses the MURANO Trial in CLL

Nicole Lamanna, MD, Associate Professor of Clinical Medicine, Columbia University Medical Center, discusses incorporating novel therapies into the standard treatment paradigm for patients with chronic lymphocytic leukemia (CLL).

The approvals of ibrutinib and idelalisib have changed the outlook for patients with CLL significantly, said Lamanna. The challenge now is determining if and how to combine these new agents with the traditional therapies used in CLL.

For younger patients, these agents may work best when combined with cytotoxics, but toxicities must be considered, said Lamanna. For older patients in their 70s or 80s, chemotherapy may not be necessary. Novel agents like ibrutinib and idelalisib may be enough on their own for patients with a shorter expected lifespan.

Nicole Lamanna, MD, Associate Professor of Clinical Medicine, Columbia University Medical Center, discusses incorporating novel therapies into the standard treatment paradigm for patients with chronic lymphocytic leukemia (CLL).


Dr. Lamanna on Incorporating Novel and Traditional Therapies in CLL 

Nicole Lamanna, MD, clinical professor of medicine, Columbia University Medical Center, discusses lymphocytosis following treatment with new oral CLL agents.

Lamanna says regular IV chemotherapy would knock down patients' blood count. Once a patient is treated with new oral agents, such as ibrutinib, the lymph nodes shrink, causing the blood count to rise. This caused some alarm in early clinical trials because researchers thought patients were progressing, Lamanna says.

Lamanna says over time, usually in a matter of months, the lymphocytosis resolves and gets better. 

Nicole Lamanna, MD, clinical professor of medicine, Columbia University Medical Center, discusses lymphocytosis following treatment with new, oral CLL agents.

Nicole Lamanna, MD

Articles

BTK Inhibitors as Frontline Therapy for CLL

Dr. Lamanna Discusses the MURANO Trial in CLL

Dr. Lamanna on Incorporating Novel and Traditional Therapies in CLL

Dr. Lamanna Discusses Lymphocytosis Following CLL Treatment