New Multiple Myeloma Treatments Present New Challenges in Side Effect Management

MM is a cancer of the plasma cells that results in the inability to fight infection and can lead to damage to the bones, kidneys, and other organs. It evolves from asymptomatic conditions that are typically diagnosed incidentally when a monoclonal protein is detected during laboratory work-up, the speakers explained. It is categorized into different types and subtypes based on the immunoglobulin produced by the myeloma cell. Most people diagnosed with MM are in their mid 60s, and it is more common in men, African Americans, and those with a family history of the disease.

For many years, MM was diagnosed based on end-organ damage or the CRAB criteria (increased calcium, renal dysfunction, anemia, and bone lesions). In 2014, the International Myeloma Working Group established diagnostic criteria that included three specific biomarkers for patients who did not have CRAB features:

• Clonal bone marrow plasma cells greater than or equal to 60%
• Serum-free light chain (FLC) ratio of at least 100, provided that the involved FLC level is 100 mg/l or higher
• More than one focal lesion on magnetic resonance imaging

MM bone disease can be diagnosed with computed tomography scan, and the use of biomarkers can predict that one or more of the CRAB criteria will occur within 18 months–2 years in patients with ultra–high-risk myeloma.

New treatment modalities are improving treatment outcomes but have also created new challenges. The medical team and patient must consider whether to use allogeneic hematopoietic stem cell transplantation (ASCT) as a first-line therapy, which is associated with prolonged progression-free survival and overall survival but does not produce a cure, or to continue with chemotherapy and plan to pursue ASCT at relapse.

ASCT may one day be considered a first-line treatment, with or without a previous ASCT, or in relapsed disease as a salvage treatment. However, it is currently reserved for young patients with high-risk myeloma in first or second relapse. Risks include graft-versus-host disease and high treatment-related morbidity and mortality. Current guidelines recommend considering ASCT only after disease relapse or as a part of a clinical trial.

“Transplant nursing is a specialty and requires rigorous training,” Georges explained, adding that patients require a conditioning regimen before transplant that consists of chemotherapy and, possibly, radiation or biotherapy. “The goal is to give the maximum amount of chemotherapy possible without permanent damage to the immune system,” Georges said.

Caring for patients after transplantation involves a careful balance of antirejection medications and techniques. Nurses must educate about hand washing, selective cohorting, attention to wounds and IV sites, and the need for immunizations. Nurses must watch for rejection by observing for skin rashes and diarrhea. Patient education is critical throughout the process.

The speakers gave an overview of common side effects associated with various other treatments, including ocular toxicities with blentamab mafodotin-blmf, infusion-related reactions with sarclisa, and a variety of lung-, breathing-, and blood-related side effects with daratumumab.

Another rapidly developing treatment is chimeric antigen receptor (CAR) T-cell therapy. Georges said that, among anti-B cell maturation antigen CAR T-cell trials, a variety of inclusion criteria, dosing strategies, lymphodepletion regimens, and CAR T-cell designs exist.

“This variety, especially considering the preliminary nature of the data, makes it difficult to compare individual CAR T cell products or draw definitive conclusions about efficacy,” Georges said. “Preliminary data shows even patients with very good initial response are at risk of disease progression.”

Georges explained that CAR T cells may be safer if used as consolidation in response to standard therapy.