Mitigating CAR T–Related Toxicities in Mantle Cell Lymphoma
Brian Hill, MD, reviews strategies for mitigating toxicities associated with CAR T-cell therapy.
Brian Hill, MD: In terms of safety, the 2 major adverse effects of the anti-CD19, CAR T-cell therapies that are available include cytokine release syndrome [CRS] and neurotoxicity. In the case of cytokine release syndrome, certain cytokines, including interleukin 6, can peak early after administration of the cell. This often correlates, or is proportional, to the degree of severity of the CRS.
One of the strategies that is used to mitigate some of the severity of cytokine release syndrome is the administration of tocilizumab, which is an anti–IL-6 receptor monoclonal antibody that blocks IL-6 signaling. This agent is now used routinely for management of CRS after CAR [chimeric antigen receptor] T-cell therapy. After the CRS passes, some patients can develop neurological toxicities, including confusion, aphasia, and in more severe cases even seizures or other manifestations of cerebral edema.
These toxicities can be very severe or life-threatening, this is why patients should be treated in the hospital, at authorized treatment centers. The optimal management of this currently is moderate to high doses of steroids—glucocorticoids, such as methylprednisolone or dexamethasone. With these approaches, we’re able to safely administer CAR T-cell therapy to most patients.
Transcript edited for clarity.
Case: A 73-Year-Old Male With Mantle Cell Lymphoma
History
- A 73-year-old man was diagnosed with mantle cell lymphoma in 2016
- He was treated with rituximab, dexamethasone, cytarabine + carboplatin followed by autologous stem cell transplant; achieved PR; continued rituximab maintenance therapy
- Ann Arbor stage IV; MIPI score 6.7, high risk
- Late 2019 he experienced clinical relapse and was started on ibrutinib; achieved SD
Currently
- He complains of a 2-month history of loss of appetite and fatigue
- PMH: hyperlipidemia, medically well-controlled
- PE: bilateral clavicular and cervical lymphadenopathy; otherwise unremarkable
- Labs: WBC 11 X 109/L, hemoglobin 9.5 gm/dL, plt 96,000/u, LDH 405 U/I, ANC 3200/mm3
- Lymph node biopsy: IHC; cyclin D1+, CD5 +, CD10+, CD20+, FISH: t (11;14)
- C/A/P CT scan: widespread lymphadenopathy including bilateral clavicular (2.4 cm, 1.5 cm), and inguinal region (4.6 cm)
- PET/CT shows diffuse uptake of 18F-FDG in the clavicular, axillary and inguinal lymph nodes
- Beta-2-microglobulin 4.1 µg/L
- ECOG PS 0
- Treatment was started with fludarabine + cyclophosphamide, followed by a single infusion of CAR T-cell therapy
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