Dr Phillips on the Shifting Treatment Paradigm For CAR T-Cell Therapy in LBCL

Adrienne Phillips, MD, MPH, hematologist/oncologist, Director of Cell Therapy and Bone Marrow Transplantation Northern Regions, RWJBarnabas Health, associate professor, medicine, Rutgers Robert Wood Johnson Medical School, discusses the impact of CAR T-cell therapy on the treatment paradigm for patients with large B-cell lymphoma, highlighting key advancements in the decision-making process for CAR T-cell therapy selection.

The emergence of CAR T-cell therapy has transformed the treatment of hematologic malignancies, particularly in B-cell lymphomas, non-Hodgkin's lymphoma (NHL), and multiple myeloma, Phillips begins. Currently, 6 CAR T-cell products have received FDA approval for various hematologic subtypes, emphasizing the substantial advancements in the space, as well as the expansion of therapeutic options, Phillips states.

Despite the plethora of available options for patients with relapsed large B-cell lymphoma (LBCL), those who have not undergone transplantation following progressing on frontline therapy typically experience a poorer prognosis of approximately 10 months, Phillips notes. However, the use of CAR T-cell therapy has caused a notable shift in survival curves for this patient population, she says. Improvements in the Kaplan-Meier curve indicate that CAR T-cell therapy could have curative potential, especially when utilized in as a second- or later-line therapy, Phillips explains.

The efficacy of CAR T-cell therapy, particularly for those who relapse within the first year or have primary refractory disease, has also affected the treatment decision-making process in LBCL, Phillips continues. Traditionally, the decision to administer CAR T-cell therapy for patients with relapsed LBCL centered around their eligibility for transplantation, she details. However, the critical question is no longer about transplant eligibility, Phillips says, adding that further chemotherapy is unlikely to provide significant benefits for patients progressing on their initial line of chemotherapy. Instead, the paradigm has evolved to emphasize whether the body's inherent immune response can be successfully harnessed through the use of immunotherapy. This focus on leveraging the body's immune system to eradicate cancer represents a substantial departure from the dogma of the past 3 decades, Phillips concludes.

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Adrienne Phillips, MD, MPH, discusses the impact of CAR T-cell therapy on the treatment paradigm for patients with large B-cell lymphoma, highlighting key advancements in the decision-making process for CAR T-cell therapy selection.

Dr Phillips on the Management of Toxicities Associated With CAR T-Cell Therapy

Adrienne Phillips, MD, MPH, hematologist/oncologist, Director of Cell Therapy and Bone Marrow Transplantation Northern Regions, RWJBarnabas Health, associate professor, medicine, Rutgers Robert Wood Johnson Medical School, discusses the management of toxicities associated with CAR T-cell therapy across hematologic malignancies.

Treatment with CAR T-cell therapies leads to a distinct toxicity profile, Phillips begins. The most important adverse effects (AEs) for patients and their providers to be made aware of are cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), she states. Patients with CRS may present with fevers, hypoxia, hypotension, and tachycardia. In certain instances, low-grade CRS can progress and become more severe, Phillips details, stating that those with high-grade CRS may require closer monitoring and blood pressure support.

Initial ICANS events occasionally resulted in fatalities in early studies of CAR T-cell therapy, Phillips continues. However, mitigation strategies involving tocilizumab (Actemra) or prednisone have significantly reduced the incidence and severity of this AE, Phillips says. The success of current approaches to toxicity management combined with the demonstrated efficacy of CAR T-cell therapies across hematologic malignancies have supported efforts to explore the feasibility of CAR T-cell administration in an outpatient setting, Phillips notes.

Meanwhile, the biological understanding of CAR T-cell–associated toxicity is evolving with novel insights into how variation in co-stimulatory domains could potentially influences AEs, Phillips expands. For example, axicabtagene ciloleucel (Yescarta;axi-cel), which has a CD28 co-stimulatory domain, is considered more toxic than lisocabtagene maraleucel (Breyanzi; liso-cel), another approved CAR T-cell product using a different co-stimulatory domain, Phillips states. This variance in co-stimulatory domains prompts further exploration into its impact on toxicity, she explains.

Despite the challenges and limitations of CAR T-cell administration, ongoing research is refining the management of patients undergoing CAR T-cell therapy. Lessons learned from early research have led to the development of effective strategies, contributing to the increased safety of this transformative therapy, Phillips emphasizes. Overall, the potential ability to administer certain CAR T-cell products in outpatient settings underscores the progress made in mitigating toxicities associated with this treatment modality, Phillips concludes.

Adrienne Phillips, MD, MPH, discusses the management of toxicities associated with CAR T-cell therapy across hematologic malignancies.

Adrienne Phillips, MD, MPH, assistant professor of clinical medicine, Columbia University Medical Center, discusses advances in the treatment of HTLV-related adult T-cell leukemia lymphoma.

Traditionally, patients with this disease have been treated with the same chemotherapies used in other aggressive lymphomas such as CHOP and EPOCH. Unfortunately, though these regimens produce high response rates, responses seen are not durable.

One trial is looking at a combination of standard chemotherapy, bortezomib, and raltegravir, an antiviral agent. Another trial is analyzing an anti-CCR4 therapy, which has shown promise in Japan, Phillips says.

Adrienne Phillips, MD, MPH

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