Dr Paz-Ares on Managing the Toxicities Associated With Newer Therapies in SCLC

“We now understand very well the [toxicity] profile of T-cell engagers, and once you know how to manage and monitor the CRS, the [ICANS], and some other toxicities, you realize [this] is not a big issue.”

Luis Paz-Ares, MD, PhD, chair of the Department of Medical Oncology at Hospital Universitario 12 de Octubre, associate professor of medicine at Universidad Complutense de Madrid, director of the Clinical and Translational Oncology Research Group at the Instituto de Investigación Hospital 12 de Octubre (imas12), and head of the H12O-CNIO Lung Cancer Clinical Research Unit, discussed how oncology teams can safely manage the distinct toxicity profiles of bispecific T-cell engagers and antibody-drug conjugates (ADCs) used in lung cancer, including cytokine release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome (ICANS), and interstitial lung disease (ILD).

According to Paz-Ares, once oncology teams learn to anticipate and manage CRS and ICANS, the toxicity profile of T-cell engagers is not a significant obstacle to treatment. He said every treatment center needs standardized protocols that the full clinical team understands, addressing which patients can be treated as inpatients vs outpatients, the required premedication, and the intensity of monitoring, which he noted should be higher during the first 2 infusions and can be relaxed thereafter. Paz-Ares added that protocols must also specify which patients experiencing CRS can be managed with supportive measures such as fluids, antipyretics, and dexamethasone, and which require escalation to the intensive care unit.

Paz-Ares said the toxicity considerations differ substantially for ADCs, which are more often associated with chemotherapy-related adverse effects such as myelosuppression, mucositis, and ocular toxicity. He noted that ILD is a complication oncology teams are less accustomed to managing with ADCs, though he said clinicians are becoming increasingly comfortable recognizing and treating it as these agents move into broader use in lung cancer. Paz-Ares concluded that as both drug classes expand into earlier lines of therapy, having clear, center-wide protocols for identifying and grading toxicity, rather than reacting case by case, will be essential to using them safely.