Adverse Event Management in Multiple Myeloma

Nurses and nurse practitioners play an important role in the management of adverse events (AEs) related to treatments for multiple myeloma (MM). A number of sessions at the ONS 2023 Congress, including “The Nurse View: Bringing Multiple Myeloma into Focus,” “New and Emerging Therapies in Multiple Myeloma: Case Studies for Nurses,” and “Myeloma: Treating Blood Cancer as a Chronic Disease,” focused on recognition of common AEs related to MM treatments. Proteasome inhibitors (PIs), immunomodulatory agents (IMiDs), and steroids have been the backbone for combination treatment regimens, and it is important for nurses to be able to recognize their associated AEs. The PI bortezomib can be associated with peripheral neuropathy, which should be assessed at each visit, while carfilzomib is associated with cardiotoxicity (especially for patients over 75 years of age), pulmonary toxicity, and venous thromboembolism (VTE). Common AEs with IMiDs include diarrhea, skin rash, myelosuppression, VTE, and secondary cancers, while steroids can be associated with emotional AEs, insomnia, hyperglycemia, hypertension, and infections. Anti-CD38 antibodies daratumumab and isatuximab can be added to combination regimens in certain patients and may be associated with their own adverse safety concerns. Treatment with these agents may interfere with the assessment of response and cross-matching as well as increase myelosuppression of background regimens and may cause infusion-related reactions as well as increased infection risk and decreased response to vaccines.

Newer FDA-approved agents targeting B-cell maturation antigen (BCMA), including chimeric antigen receptor T-cell (CAR-T cell) therapy and bispecific antibodies, may have serious associated risks including cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS). In clinical trials with CAR-T cell therapy, all-grade CRS occurred in 84% of patients treated with idecabtagene vicleucel (ide-cel) and 95% of patients treated with ciltacabtagene autoleucel (cilta-cel), while ICANS occurred in 18% treated with ide-cel and 21% treated with cilta-cel. Rates of all-grade CRS with bispecific antibody teclistamab were 72% (all events were grade 1/2, except 1 transient) in clinical trial, and 5 patients had a total of 9 ICANS events, all grade 1/2. There were no treatment discontinuations or dose reductions due to neurotoxic events, including ICANS. CRS can range from mild to life-threatening; early recognition and treatment are vital in patients. Signs and symptoms of CRS can include fever, fatigue, arthralgia, headache, nausea and vomiting, hypotension, coagulopathy, pulmonary edema, and cardiac and/or renal failure. It is important to monitor vital signs, including temperature and O₂ saturation, and review systems during a physical exam specifically focusing on cardiovascular, pulmonary, and neurologic systems. Laboratory monitoring is important in recognizing CRS including C-reactive protein, cytokines, ferritin, and lactate dehydrogenase, and clinicians should rule out infection. Management of CRS is institution specific and may include treatment with tocilizumab, steroids, and supportive care. In the MajesTEC-1 study with teclistamab, CRS was managed with premedication, step-up dosing, and prompt diagnosis and intervention. A poster titled “Cytokine Release Syndrome: An Educational Intervention for Oncology Nurses” presented by Rosalynn Ofel Sanchez detailed interventions that can help increase nurse recognition and understanding of CRS. It was found that, after intervention with a training module either virtually or in person, nurses’ knowledge of CRS onset, patient education, and treatment modalities increased with an overall improvement in knowledge across categories. Neurotoxicity is rare in these patients but can potentially be serious. Monitoring for ICANS can be done using the Immune Effector Cell Encephalopathy screening tool and review of symptoms focusing on neurologic. If ICANS is suspected, perform neuroimaging, ideally with MRI, and a diagnostic lumbar puncture. Signs and symptoms of neurotoxicity can include confusion, seizure, tremor, hallucinations, encephalopathy, and difficulty finding words. Treatment can include levetiracetam and supportive care; corticosteroids are indicated for ICANS grade 2 or higher. Infection is another common AE with BCMA-targeting agents; in clinical trials, serious infections occurred in 69% of patients treated with ide-cel, 58% treated with cilta-cel, and 30% of patients treated with teclistamab. Patients may require viral prophylaxis until CD4 counts are >200, pneumocystis jiroveci pneumonia prophylaxis, granulocyte colony-stimulating factor for higher-grade neutropenia, and IV immunoglobulin for IgG <400.