Dr Deng on the Evolution of the Hodgkin Lymphoma Treatment Paradigm

Changchun Deng, MD, PhD, associate professor, hematology/oncology, University Hospitals Seidman Cancer Center; member, Immune Oncology Program, Case Comprehensive Cancer Center, discusses the evolution of Hodgkin lymphoma management following data readouts at the 

Developments are underway in the field of Hodgkin lymphoma, particularly with advancements in upfront treatment strategies, Deng begins, saying that one of the latest approaches involves incorporating a PD-1–directed antibody into initial therapies. This innovation aims to maximize the efficacy of first-line treatments for patients, Deng says. Notably, one of the leading PD-1–directed antibodies being used in this context is nivolumab (Opdivo), he explains. Nivolumab was being combined with the standard AVD (Adriamycin, vinblastine, dacarbazine) chemotherapy regimen in the phase 3 SWOG S1826 trial (NCT03907488). The data on this combination were presented at the 2023 ASH Annual Meeting and the trial has yielded notable results, Deng reports. This treatment approach represents a step forward in the management of Hodgkin lymphoma, demonstrating enhanced therapeutic outcomes, he adds.

In addition to the nivolumab/AVD combination, there is also emerging research on 

the efficacy of combining nivolumab with brentuximab vedotin (Adcetris),

 an anti-CD30 antibody-drug conjugate, Deng continues. This regimen is particularly notable for its chemotherapy-free nature and its high response rates in patients with Hodgkin lymphoma, he explains. Studies have shown that administering these 2 agents together can achieve a near-100% response rate, underscoring the potential for substantial progress in treating patients with this disease, Deng elucidates. For patients with early-stage Hodgkin lymphoma, the prospect of receiving 2 drugs with a potential for nearly 100% cure rates is vital, he notes.

The integration of PD-1–directed antibodies, such as nivolumab, into first-line treatment regimens for Hodgkin lymphoma signifies a shift in therapeutic strategies, Deng continues. The combination of nivolumab with established chemotherapy or with other targeted agents, such as brentuximab vedotin,holds promise for improving treatment outcomes and ultimately curing more patients, especially those diagnosed at earlier stages of Hodgkin lymphoma, emphasizing the potential to impact the standards of care, he concludes.

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Changchun Deng, MD, PhD, discusses the evolution of Hodgkin lymphoma management following data readouts at the 2023 ASH Annual Meeting.

Dr Deng on BTK Inhibitors vs Venetoclax-Based Treatment Regimens in CLL/SLL

Changchun Deng, MD, PhD, associate professor, hematology/oncology, University Hospitals Seidman Cancer Center; member, Immune Oncology Program, Case Comprehensive Cancer Center, discusses considerations for covalent BTK inhibitors vs venetoclax (Venclexta)–based treatment regimens for patients with chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL).

Several key considerations guide CLL/SLL management, including the presence of high-risk genetic factors, notably 

 mutations and 17p deletions, which significantly influence oncologists’ choices of therapy, Deng says. Although other disease factors, such as 11q deletions and unmutated IGHV status, are considered high-risk features, they may not weigh as heavily in the decision-making process compared with 

 mutations and 17p deletions due to their implications on treatment response, he says.

For patients with both a 17p deletion and a 

 mutation who require treatment, a covalent BTK inhibitor is typically favored, especially if patients are open to receiving therapy indefinitely, Deng continues. Currently, there are 3 approved covalent BTK inhibitors: zanubrutinib (Brukinsa), acalabrutinib (Calquence), and ibrutinib (Imbruvica). The choice among these inhibitors is nuanced and may depend on factors such as the patient's risk of developing atrial fibrillation, a notable concern associated with BTK inhibitors, making individualized treatment selection paramount, he reports.

The decision to use a covalent BTK inhibitor vs a BCL-2 inhibitor such as venetoclax is intricately linked to patient preferences and long-term disease management strategies, Deng expands. Covalent BTK inhibitors offer a continuous treatment approach suitable for patients willing to commit to ongoing therapy, according to Deng. In contrast, venetoclax-based regimens, particularly when combined with anti-CD20 monoclonal antibodies, may present a time-limited treatment option with the potential for yielding deep remissions, including minimal residual disease negativity, he adds.

Ultimately, the choice between a covalent BTK inhibitor and a venetoclax-based regimen involves a comprehensive assessment of genetic risk factors; patient preferences regarding treatment duration and regimen tolerability; and considerations of the evolving CLL/SLL treatment armamentarium, Deng concludes.

Changchun Deng, MD, PhD, discusses considerations for covalent BTK inhibitors vs venetoclax-based treatment regimens for chronic lymphocytic leukemia.

Dr Deng on the Benefits of Pirtobrutinib in CLL

Changchun Deng, MD, PhD, associate professor, hematology/oncology, University Hospitals Seidman Cancer Center; member, Immune Oncology Program, Case Comprehensive Cancer Center, discusses the mechanism of action of the noncovalent BTK inhibitor pirtobrutinib (Jaypirca) and the advantages that are associated with this agent for the treatment of patients with previously treated chronic lymphocytic leukemia (CLL).

When determining what treatment a patient with CLL should receive, oncologists should consider the patient’s overall health, cardiac function, and treatment history, Deng says. One option for these patients is the novel noncovalent BTK inhibitor pirtobrutinib, which 

 in 2023 for the treatment of adult patients with CLL or small lymphocytic lymphoma (SLL) who have received 2 or more prior lines of therapy, including a BCL-2 inhibitor and a BTK inhibitor.

Although all BTK inhibitors share the same target, noncovalent agents target BTK differently than covalent BTK inhibitors, and can therefore be used in patients who have previously received covalent agent, Deng notes. In the CLL/SLL cohort (n = 110) of the pivotal phase 1/2 BRUIN trial (NCT03740529), 98% of patients had received 2 or more prior lines of systemic therapy. At an estimated median follow-up of 15.7 months, pirtobrutinib elicited an overall response rate of 72% (95% CI, 63%-80%), all of which were partial responses. The median time to response was 3.7 months (range, 1.7-27.9), and the median duration of response was 12.2 months (95% CI, 9.3-14.7).

Furthermore, the safety profile of pirtobrutinib is favorable when compared with that of covalent BTK inhibitors that are FDA approved in CLL, such as ibrutinib (Imbruvica), acalabrutinib (Calquence), and zanubrutinib (Brukinsa), Deng emphasizes. For instance, pirtobrutinib is associated with lower levels of cardiac toxicity, Deng concludes. The most common serious AEs with pirtobrutinib in the BRUIN trial were pneumonia (18%), COVID-19 (9%), febrile neutropenia (7%), and sepsis (7%).

Changchun Deng, MD, PhD, discusses the mechanism of action and advantageous features of pirtobrutinib for patients with chronic lymphocytic leukemia.

Changchun Deng, MD, PhD

Articles

Dr Deng on the Evolution of the Hodgkin Lymphoma Treatment Paradigm

Dr Deng on BTK Inhibitors vs Venetoclax-Based Treatment Regimens in CLL/SLL

Dr Deng on the Benefits of Pirtobrutinib in CLL