Offering prophylactic treatment before immunotherapy could significantly reduce the rate of cytokine release syndrome in multiple myeloma patients, a new US study has found.
Treatment breakthroughs, such as the immunotherapy drug teclistamab, can lead to potentially lethal side effects, including cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS).
The newly published research, from Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, indicates prophylactic treatment before immunotherapy could be beneficial to prevent severe complications – though further confirmatory studies are needed.
The findings of the study, published in the latest Blood Cancer Discovery, could remove the need for long hospital stays to administer teclistamab and other immunotherapies, which would broaden access to more cancer patients.
Co-corresponding author Dr Ola Landgren, chief of the Division of Myeloma at Sylvester, said: “In an ideal world, you could pre-medicate patients against CRS and treat them in an outpatient setting. As a result, there is huge interest in this possibility worldwide.”
Teclistamab and similar immunotherapies are bispecific T-cell engagers that get T-cells to attack and shrink tumours. A previous study, published in the New England Journal of Medicine, found teclistamab produced an overall response rate of 63% in multiple myeloma patients whose tumours had failed to respond to multiple previous therapies or had become resistant to them. The drug received FDA approval for use with these patients in 2022, followed by two other bispecific T-cell engagers.
However, because these immunotherapy drugs increase the immune system’s activity against a tumour, the process can lead to an overactive immune response, the hallmark of CRS.
CRS is treated with drugs that counteract the cytokine release that causes T-cells to go into overdrive. Often these drugs are administered after symptoms have developed, but there is growing interest in giving the treatments as a preventative measure.
Dr Landgren and colleagues reviewed preliminary data from a 2022 study on multiple myeloma patients treated prophylactically with tocilizumab, which showed the approach eased CRS in patients receiving a bispecific T-cell engager.
They conducted their own study, which included 31 multiple myeloma patients being treated with teclistamab. In the study, only 13% developed CRS after prophylactic treatment with tocilizumab compared to 72% observed in an earlier study treating patients for CRS as symptoms arose. Additionally, patients in this newer study had less severe CRS and lower rates of its recurrence.
This preventive approach also appeared to ease ICANS, while patients receiving CAR-T cell immunotherapy also benefit from prophylactic CRS treatment, according to the researchers.
“The field of myeloma is probably one of the biggest examples of successful drug development in modern times,” said Dr Landgren. “We are going with full steam into an era of immunotherapy.”
Kowalski A, Lykon J, Diamond B, Coffey DG, Kaddoura M, Maura F, Hoffman JE, Kazandjian D, Landgren O. (2024) “Emerging Strategies for the Prevention of Immune Toxicities Associated with T-cell-Engaging Cancer Therapies.” Blood Cancer Discovery, doi: 10.1158/2643-3230.BCD-23-0228.
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