Barry Paul, MD, assistant professor, the Division of Plasma Cell Disorders, the Department of Hematologic Oncology and Blood Disorders, Atrium Health, discusses the emerging benefits of integrating CAR T-cell therapy into treatment paradigms for patients with relapsed/refractory multiple myeloma.

The treatment of patients with multiple myeloma traditionally requires continuous rounds of chemotherapy to be administered until disease progression or tolerance is reached. However, CAR T-cell therapy is typically administered as a single infusion and continues to expand and proliferate in the absence of continued administration, making reinfusion largely unnecessary, Paul explains. This unique feature makes CAR-T cell therapy an attractive option for both patients and physicians. 

Despite this, researchers are still developing methods to optimize the efficacy of CAR T-cell therapy in clinical practice. Identifying adjunctive therapies that allow CAR T-cell therapies to persist for longer could lead to a more robust patient response, Paul notes. Similarly, efforts to improve the sequencing of T-cell mediated therapies, including CAR T-cell therapy, bispecific antibodies, and antibody-drug conjugates, could allow practitioners to identify the most effective treatment option for different patient populations. Both areas necessitate more research, Paul concludes.

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Barry Paul, MD, discusses the emerging benefits of integrating CAR T-cell therapy into treatment paradigms for patients with relapsed/refractory multiple myeloma.

Dr. Paul on the Future of CAR T-Cell Therapy in Multiple Myeloma Treatment

Barry Paul, MD, assistant professor, the Division of Plasma Cell Disorders, the Department of Hematologic Oncology and Blood Disorders, Atrium Health, discusses the management of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) following CAR T-cell therapy in cancer care.

CRS and ICANS are both adverse effects (AEs) linked to CAR T-cell therapy and any cellular-based therapy, Paul says.

CRS is a systemic inflammatory response that is secondary to the activation of bystander immune and non-immune cells, Paul adds. The activation of these cells leads to significant increase in interleukin-1 (IL-1) and IL-6, causing fever, fatigue, headaches, arthralgias, and myalgias, Paul notes. More severe cases of CRS can present with hypotension, shock, or multi-system organ failure, Paul adds. CRS can be managed with tocilizumab (Actemra) if supportive care with antipyretics, acetaminophen, supplemental oxygen, and intravenous fluids, is not effective, Paul says.

Though ICANS presents with similar symptoms to CRS, this AE can disturb the blood-brain barrier gets disturbed, allowing cytokines to penetrate the central nervous system (CNS), Paul continues. ICANs can present with more CNS symptoms, including headache, confusion, and impaired motor skills, Paul explains, nothing that more severe cases of ICANS can lead to aphasia, seizures, cerebral edema, or coma. Since tocilizumab is ineffective due to its inability to cross the blood-brain barrier, high-dose corticosteroids are utilized for patients with ICANS, Paul concludes.

Barry Paul, MD, discusses the management of cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome following CAR T-cell therapy in cancer care.


Dr. Paul on the Management of CRS and ICANS After CAR T-cell Therapy in Cancer Care

Barry A. Paul, MD, hematologist, Levine Cancer Institute, Atrium Health, discusses the role of carfilzomib (Kyprolis) in the treatment of patients with relapsed/refractory multiple myeloma.

Carfilzomib has demonstrated impressive efficacy in patients with relapsed/refractory disease, including those who are refractory to another proteasome inhibitor such as bortezomib (Velcade), says Paul.

However, the utility of carfilzomib is evolving as the drug is being given more frequently in the frontline setting, explains Paul. As such, patients who become refractory to carfilzomib in the first-line setting will not receive a carfilzomib-based regimen upon relapse.

The phase III ARROW study demonstrated prolonged progression-free survival with once-weekly carfilzomib at 70 mg/m

 compared with twice-weekly carfilzomib at 27 mg/m

. Moreover, the once-weekly regimen was associated with less toxicity versus the twice-weekly regimen, says Paul.

More patients who received once-weekly carfilzomib required dose reductions due to minor toxicities versus those who received the twice-weekly regimen, explains Paul. Additionally, more grade ≥3 adverse events were noted in patients who received carfilzomib once-weekly.

In October 2018, the FDA approved the once-weekly regimen of carfilzomib for use in combination with dexamethasone in patients with relapsed/refractory myeloma based on these data. The once-weekly regimen may provide a more convenient option for patients, concludes Paul.

Barry A. Paul, MD, discusses the role of carfilzomib in the treatment of patients with relapsed/refractory multiple myeloma.

Barry A. Paul, MD

Articles

Dr. Paul on the Future of CAR T-Cell Therapy in Multiple Myeloma Treatment

Dr. Paul on the Management of CRS and ICANS After CAR T-cell Therapy in Cancer Care

Dr. Paul on the Role of Carfilzomib in Relapsed/Refractory Multiple Myeloma