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Introduction: Multiple myeloma (MM) is an incurable bone marrow (BM)-based cancer involving clonal plasma cells. Most patients show elevated levels of serum monoclonal protein (sMP) and kappa or lambda serum free light chains (sFLCs) at diagnosis. However, around 1–2% of patients, termed nonsecretory, do not produce these biomarkers. As the disease progresses, more patients may become unevaluable using conventional markers, requiring invasive and expensive procedures like BM biopsies and positron emission tomography-computed tomography (PET-CT) scans for assessment and highlighting the need for alternative methods to monitor disease progression. Case Presentation: We present a case report of an MM patient who developed nonsecretory disease during his second line of treatment when he complained of new rib pain; progressive disease was then confirmed on a PET-CT scan. The patient showed an increase in his serum B-cell maturation antigen (sBCMA) levels whereas his conventional myeloma markers did not detect disease activity (sMP remained undetectable and involved sFLC level was normal). After starting a new treatment regimen, his rib pain disappeared, PET-CT scan improved, and sBCMA levels decreased. Upon relapse, he developed increased rib pain with a rising sBCMA level; his conventional myeloma markers did not detect disease activity. After changing to a new regimen, his rib pain improved, and this was accompanied by a decrease in his sBCMA levels. Conclusion: Thus, this case exemplifies the potential for sBCMA to provide a non-invasive method for monitoring MM patients who develop nonsecretory disease.

Despite major therapeutic advancements in recent years, multiple myeloma (MM) remains an incurable disease with nearly all patients experiencing relapsed and refractory disease over the course of treatment. Extending the duration and durability of clinical responses will necessitate the development of therapeutics with novel targets that are capable of robustly and specifically eliminating myeloma cells. B-cell maturation antigen (BCMA) is a membrane-bound protein expressed predominantly on malignant plasma cells and has recently been the target of several novel therapeutics to treat MM patients. This review will focus on recently approved and currently in development agents that target this protein, including bispecific antibodies, antibody-drug conjugates, and chimeric antigen receptor T-cell therapies. In addition, this protein also serves as a novel serum biomarker to predict outcomes and monitor disease status for MM patients; the studies demonstrating this use of BCMA will be discussed in detail.

Abstract Background Multiple myeloma (MM) patients have variable responses to mRNA vaccination to COVID‐19. Little is known regarding their vaccine‐induced antibody levels over time. Methods We monitored spike IgG antibody levels over 24 weeks among a subset of 18 MM patients who showed a full response after two mRNA vaccinations. Results MM patients had a more rapid decline in antibody levels as compared to eight healthy controls, with power law half‐lives of 72 days (vs. 107 days) and exponential half‐lives of 37 days (vs. 51 days). The patients with longer SARS‐CoV‐2 antibody half‐lives were more likely to have undetectable monoclonal protein than those with shorter half‐lives, suggesting better disease control may correlate with longer duration of vaccine‐induced antibodies. Regardless, by 16 weeks post‐second dose of mRNA vaccination, the majority of patients had antibody levels below 250 binding arbitrary units per milliliter, which would be unlikely to contribute to preventing COVID‐19. Conclusions Thus, even MM patients who respond adequately to vaccination are likely to require more frequent booster doses than the general population.

Background: Patients with multiple myeloma have unpredictable responses to vaccination for COVID-19. Anti-spike antibody levels can determine which patients develop antibodies at levels similar to healthy controls, and are a known correlate of protection. Case report: A multiple myeloma patient developed protective anti-spike antibodies after vaccination (608 IU/mL), but nonetheless developed severe breakthrough COVID-19 just 10 weeks following his second vaccination with mRNA-1273. Results: Sequencing of the viral isolate revealed an extensively mutated variant with 10 spike protein mutations, including E484Q and N440K. Serology testing showed a dramatic decline in anti-spike antibodies immediately prior to virus exposure. Conclusions: Multiple myeloma patients who do develop detectable antibody responses to vaccination may be at increased risk for breakthrough infections due to rapid decline in antibody levels. Viral variants with immune escape mutations such as N440K, also seen independently in the SARS-CoV-2 Omicron variant (B.1.1.529) and in viral passaging experiments, likely require a higher level of anti-spike antibodies to prevent severe COVID-19.