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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.

We have reported that IgG antibody responses following two mRNA COVID-19 vaccinations are impaired among patients with multiple myeloma (MM). In the current study, sixty-seven patients with MM were tested for anti-spike IgG antibodies 0–60 days prior to their first vaccination, 14–28 days following the second dose, and both before and 14–28 days after their third dose of the mRNA-1273 or BNT162b2 vaccines. After the first two doses, most patients' (93 %) antibody levels declined to ineffective levels ( 10-fold change from baseline for the two-dose series, switching from BNT162b2 to mRNA-1273 for D3, and treatment with elotuzumab and an immunomodulatory agent. Lower antibody levels prior to D3, poorer overall response to first two doses, and ruxolitinib or anti-CD38 monoclonal antibody treatment negatively correlated with D3 response. Our results show encouraging activity of the third vaccine, even among patients who failed to respond to the first two vaccinations. The finding of specific factors that predict COVID-19 antibody levels will help advise patients and healthcare professionals on the likelihood of responses to further vaccinations.