Eduardo Sotomayor, MD, discusses the current arsenal of BTK inhibitors in chronic lymphocytic leukemia.

Dr Sotomayor on the Integration of BTK Inhibitors into the CLL Treatment Arsenal

Eduardo Sotomayor, MD, director, Cancer Institute, Tampa General Hospital, discusses the current arsenal of BTK inhibitors in chronic lymphocytic leukemia (CLL), detailing how this drug class has advanced the CLL treatment paradigm.

State of the Science Summit™ on leukemia and lymphoma, which was chaired by Sotomayor, oncologists such as Javier Pinilla, MD, PhD, MD, of the Moffitt Cancer Center, discussed the sequencing of BTK inhibitors in CLL. Expanding on this presentation, Sotomayor notes that having multiple first-generation and second-generation BTK inhibitors available for use in CLL is a positive development, offering physicians flexibility in tailoring therapy to individual patient needs.

There are currently 3 covalent BTK inhibitors approved for use in CLL, Sotomayor states. In February 2014, 

 for patients with pretreated CLL and was subsequently 

received FDA approval for patients with CLL

zanubrutinib received FDA approval for patients with CLL

 or small lymphocytic lymphoma (SLL). The latest addition to the treatment arsenal in CLL is the noncovalent BTK inhibitor pirtobrutinib (Jayprica), which 

 for adult patients with CLL or SLL who previously received 2 or more prior lines of therapy, including a BTK inhibitor and a BCL2 inhibitor, in December, 2023.

Although the efficacy of these covalent BTK inhibitors appears similar, differences in adverse effects (AEs) allow physicians to select the agent they are most comfortable with and have the most experience using, Sotomayor notes. These agents have greatly advanced the management of CLL, Sotomayor says, adding that these agents have revolutionized approaches from the previously used combination of fludarabine, bendamustine, and rituximab (Rituxan).

However, it's important to note that targeted therapies like BTK inhibitors also come with their own set of AEs, underscoring the need for careful monitoring and management of patients undergoing treatment, Sotomayor adds. Overall, the availability of multiple BTK inhibitors has transformed the landscape of CLL treatment, offering improved efficacy and tolerability compared to traditional chemotherapy regimens, he concludes.

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Eduardo Sotomayor, MD, professor of medicine, Department of Hematology and Oncology, and director, GW Cancer Center, discusses the durability of CAR T cells, as well as ways to combat immune escape mechanisms in hematologic malignancies.  

CAR T cells can potentially persist for months or years, Sotomayor says. Moreover, the patient’s natural immune response can generate memory cells that attack recurrent cancer cells and allow continued clinical remission. 

This is contingent on whether the cancer cells continue to express the molecule targeted by the CAR T cells like CD19 for example, or if they develop a mechanism of escape to avoid targeting and continue proliferation, Sotomayor says. 

However, he adds, treatment is evolving to combat these mechanisms of escape by targeting multiple antigens such as CD20 or CD22. Due to tumor heterogeneity, this appears to be a lucrative strategy. Currently, there are ongoing clinical trials exploring this idea. 

Eduardo Sotomayor, MD, professor of medicine, Department of Hematology and Oncology, and director, GW Cancer Center, discusses the durability of CAR T cells, as well as ways to combat immune escape mechanisms in hematologic malignancies.  
 

Dr. Sotomayor on the Durability of CAR T Cells in Hematologic Malignancies

Eduardo Sotomayor, MD, professor of medicine, Department of Hematology and Oncology, and director, GW Cancer Center, discusses differences between FDA-approved CAR T-cell therapies.

There are 2 FDA-approved CD19-directed CAR T-cell therapies: axicabtagene ciloleucel (axi-cel; Yescarta) and tisagenlecleucel (Kymriah). Both products are approved for the treatment of relapsed/refractory non-Hodgkin lymphoma, but tisagenlecleucel is also approved for pediatric patients with acute lymphoblastic leukemia. Although both products target CD19, they have different co-stimulatory domains, explains Sotomayor. CD28 is the costimulatory domain for axi-cel, whereas 4-1BB is the costimulatory domain for tisagenlecleucel. CAR T cells that rely on CD28 are more potent but have a shorter half-life, adds Sotomayor. Conversely, 4-1BB is less potent but has greater CAR T-cell persistence.

Now, researchers are investigating ways to extend the persistence of CD28 costimulatory products without decreasing efficacy. Research is also being dedicated to minimizing the toxicities associated with these products by modulating inflammatory cytokines, says Sotomayor. This approach may reduce the incidence of cytokine release syndrome and neurotoxicity.

Dr. Sotomayor on Differences Between FDA-Approved CAR T-Cell Therapies

Eduardo Sotomayor, MD, the Susan and John Sykes Endowed Chair in Hematologic Malignancies at Moffitt Cancer Center, discusses how personalized medicine may eventually help with preventing cancer.

One of the major advances in understanding genetic variations of tumors is next-generation sequencing, Sotomayor explains. This allows practitioners to perform a detailed analysis of tumors or cancer cells, specifically looking at any abnormal genes. This advancement has led researchers to understand many basic causes of cancer.

As a next step, Sotomayor says researchers should now examine lesions that have the potential to become malignant, and work to identify biomarkers and genetic variations in them. This advancement would take place in patients at high risk of developing cancer in the next 1 to 2 years; therefore, an invention could take place with preventative measures and lifestyle changes.

Eduardo Sotomayor, MD, the Susan and John Sykes Endowed Chair in Hematologic Malignancies at Moffitt Cancer Center, discusses how personalized medicine may eventually help with preventing cancer. 

Dr. Sotomayor on Personalized Medicine Preventing Cancer

Eduardo Sotomayor, MD, the Susan and John Sykes Endowed Chair in Hematologic Malignancies at Moffitt Cancer Center, discusses the future of personalized medicine in lymphoma.

Personalized medicine, also known as precision medicine, has more potential than just its current use for the treatment of cancer, says Sotomayor.  Although it is not possible yet, he believes in the future personalized medicine will be primarily used for the prevention of cancer.

Both therapy, and prevention strategies will be based on patients’ genetic information, lifestyle, diet, and other environmental factors. 

View more from the 2015 Congress on Hematologic Malignancies

Eduardo Sotomayor, MD

Articles

Dr Sotomayor on the Integration of BTK Inhibitors into the CLL Treatment Arsenal

Dr. Sotomayor on the Durability of CAR T Cells in Hematologic Malignancies

Dr. Sotomayor on Differences Between FDA-Approved CAR T-Cell Therapies

Dr. Sotomayor on Personalized Medicine Preventing Cancer

Dr. Sotomayor on Precision Medicine for the Prevention of Cancer