Dr Shouse on the Importance of NGS Testing in Follicular Lymphoma

Geoffrey Shouse, DO, PhD, assistant professor, Division of Lymphoma, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, discusses the importance of testing for genetic abnormalities through next-generation sequencing (NGS) in patients with follicular lymphoma (FL).

NGS plays a crucial role in identifying genetic abnormalities in FL, though its full potential is still being realized, Shouse begins. The field of NGS is rapidly advancing and will likely prove useful at various levels as researchers continue to explore its applications, according to Shouse. One promising use of NGS is identifying therapeutic targets in patients whose disease has relapsed multiple times, particularly when standard treatments are no longer effective, he explains. NGS can also detect high-risk mutations, such as 

, which are known to confer resistance to chemotherapy, making it crucial to tailor treatment strategies for these patients accordingly, Shouse reports.

In current practice, NGS is particularly valuable for selecting patients who may benefit from targeted therapies, Shouse continues. For example, in FL, 

 mutations are routinely screened for when considering treatment with tazemetostat (Tazverik), as these mutations are associated with a higher likelihood of response, Shouse states. Although resistance mechanisms like 

 mutations have been observed in other cancers, such as chronic lymphocytic leukemia, their role in FL remains unclear, he reiterates. As the use of BTK inhibitors increases in the FL setting, it will be important to investigate these resistance mechanisms further, Shouse emphasizes.

Looking ahead, the potential for targeted therapies in FL is significant, especially when considering combination treatments, Shouse expands. Because targeted therapies are generally well tolerated, they can be combined with other treatments without introducing excessive toxicity, Shouse explains. By targeting multiple pathways from the outset, there is potential for achieving deeper and more durable remissions, leading to prolonged disease control, he says. Although combination therapies are still in the early stages of testing in FL, their future potential is substantial and has yet to be fully explored, Shouse concludes.

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Geoffrey Shouse, DO, PhD, discusses the importance of performing next-generation sequencing in patients with follicular lymphoma.

Dr Shouse on AEs Associated With Targeted Therapies in FL

Geoffrey Shouse, DO, PhD, assistant professor, Division of Lymphoma, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, discusses adverse effects (AEs) associated with targeted therapies used to treat patients with follicular lymphoma (FL), highlighting how he determines which patients would benefit most from these novel approaches.

AEs associated with cancer treatments vary by drug class, Shouse begins. For example, lenalidomide (Revlimid), a cereblon inhibitor, is linked to an increased risk of thrombosis, he states. To manage this, investigators assess a patient’s baseline thrombosis risk and provide preventive medication, often aspirin or blood thinners, depending on their history of thrombosis and overall risk level, Shouse states. On the other hand, BTK inhibitors, such as zanubrutinib (Brukinsa), commonly raise concerns about bleeding, irregular heart rhythms, and low blood counts, he adds.

Low blood counts are generally manageable with growth factors and prophylactic medications to prevent infections, he continues. For bleeding, Shouse says that treating oncologists should closely monitor patients, and in cases of severe bleeding, the treatment dosage may be reduced or switched altogether. Irregular heart rhythms are also monitored, and although studies indicate that patients with baseline arrhythmias may still tolerate BTK inhibitors like zanubrutinib, investigators should manage these conditions as they arise, he notes. However, if heart issues worsen, discontinuing the drug may be necessary, Shouse emphasizes.

Overall, targeted therapies for patients with FL are generally well tolerated, but the key is to consider any pre-existing conditions or toxicities, he states. For instance, patients with poorly controlled atrial fibrillation may not be ideal candidates for BTK inhibitors, and those with a history of severe bleeding episodes or multiple thromboses might not be suitable for treatments such as lenalidomide, he elucidates. It is also important to note that tailoring treatment based on individual risk factors ensures patients receive the most appropriate and safe therapy, Shouse concludes.

Geoffrey Shouse, DO, PhD, discusses adverse effects associated with targeted therapies used to treat patients with follicular lymphoma.

Dr Shouse on Currently Available Targeted Therapies for FL

Geoffrey Shouse, DO, PhD, assistant professor, Division of Lymphoma, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, discusses currently available targeted therapies for the treatment of patients with follicular lymphoma (FL) and compares the utility of targeted therapies vs traditional chemotherapy.

Over the years, significant advancements have been made in the development of targeted therapies for FL, and several molecular targets have emerged as promising avenues for treatment, Shouse begins. One notable development in PI3K inhibitors was the introduction of copanlisib (Aliqopa) in FL, 

, he reports. In contrast, the BTK inhibitor 

combination with obinutuzumab (Gazyva) received

 in March 2024 for the treatment of patients with relapsed/refractory FL.

Lenalidomide (Revlimid) was one of the first targeted therapies to gain FDA approval for FL, specifically in combination with rituximab (Rituxan), he continues. This combination can also be used in the frontline treatment setting. Another treatment option is tazemetostat (Tazverik), which has been approved for use in the third-line setting. However, ongoing research indicates that tazemetostat may hold promise when used in combination regimens earlier in the treatment process, Shouse explains.

The distinction between targeted therapies and traditional chemotherapy is significant, he continues. Traditional chemotherapy is designed to target rapidly dividing cells, which often results in the destruction of both cancerous and healthy cells, leading to substantial toxicity, according to Shouse. In contrast, targeted therapies are engineered to focus on specific pathways active within cancer cells, he says, noting that this approach allows for a more precise attack on the cancer and minimal damage to healthy cells, thereby reducing toxicity.

Additionally, many targeted therapies offer the advantage of oral administration, which is more convenient for patients compared with the intravenous administration of chemotherapy, Shouse adds. This ease of use, combined with potentially lower toxicity, makes targeted therapies a compelling option for treating patients with FL, he concludes.

Geoffrey Shouse, DO, PhD, discusses currently available targeted therapies for the management of follicular lymphoma.

Geoffrey Shouse, DO, PhD

Articles

Dr Shouse on the Importance of NGS Testing in Follicular Lymphoma

Dr Shouse on AEs Associated With Targeted Therapies in FL

Dr Shouse on Currently Available Targeted Therapies for FL