Treatments for NHL can cause a variety of adverse effects.
Common adverse events of chemotherapy include myelosuppression, neutropenic fever, and immunosuppression. Myelosuppression can be treated with transfusions (red cells and platelets) or the administration of colony-stimulating factors (eg, granulocyte colony-stimulating factor). Neutropenia leads to an increased risk of infections from bacteria, viruses, and fungi. Patients are also susceptible to infections like Varicella and herpes zoster and managed by post-exposure prophylaxis against varicella-zoster infection. Other common adverse effects include hair loss, mouth sores, loss of appetite, nausea and vomiting, diarrhea or constipation, increased risk of infection, heart failure, bleeding or bruising after minor cuts or injuries, fatigue and shortness of breath.1
Radiotherapy can cause heart failure by causing diffuse fibrosis in the interstitium of the myocardium and progressive fibrosis of pericardial layers, cells in the conduction system, and the cusps or leaflets of the valves. The left ventricular ejection fraction is usually preserved. Vincristine can cause neurotoxicity. Other adverse effects include gastrointestinal symptoms, such as constipation, diarrhea, dry mouth, and mouth sores.1
Long-term survivors of NHL have an elevated risk of developing a second malignancy. The risk of developing a second malignancy varies based on the subtype of NHL and the treatment received. Depending on the area of radiation, patients can develop squamous cell carcinoma of the head and neck and breast cancer.1
Radiation to the neck and mediastinum can result in hypothyroidism. Patients undergoing hematopoietic cell transplantation with total body irradiation (TBI) conditioning were documented to suffer from growth hormone deficiency, hypogonadism, insulin resistance, and dyslipidemia.1
Hematopoietic cell transplantation can lead to neurologic and psychiatric complications like post-traumatic stress disorder.1
CAR T-cell therapy: Several clinical studies indicate that CAR T cell therapy can cause serious adverse events (SAEs) in patients with NHL (Figure 1). The SAEs can affect any organ system of the body and can develop into multiple organ failure in severe cases, endangering life.2
The key adverse events associated with bispecific antibody therapy are cytokine release syndrome (CRS), neurotoxicity, infections and tumor lysis syndrome (Figure 2). CRS is characterized by an exaggerated inflammatory response with elevated levels of cytokines interleukin-2 (IL-2), interleukin-6 (IL-6), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNFα). The clinical symptoms of CRS range from mild fever and malaise to severe hypotension and hypoxia. In the ELM-1 and ELM-2 clinical studies, modified step-up dose regimen showed favorable safety profile. The safety profile was generally consistent with earlier reports and CRS events were predominantly low grade and manageable. Importantly, continued treatment with odronextamab showed no detrimental effects on patient-reported outcomes.4
The severity of CRS is graded according to guidelines from the American Society for Transplantation and Cellular Therapy (ASTCT). Grades 1 and 2 are more common and characterized by non-life-threatening symptoms, whereas grades 3 and 4 require urgent intervention due to the life-threatening nature of symptoms (Figure 3). Management of CRS and neurotoxicity based on the grade is shown below (Figure 4).3,5
Comprehensive, consensus-based recommendations specific to the assessment and management of BsAb-related toxicities from international panel of academic and community practice physicians, advanced practitioners, registered nurses and pharmacists with experience using CD3xCD20 BsAbs7
