Diagnosed with myeloma before age 40

In this issue of Blood, Caulier et al report clinical epidemiology data from a retrospective cohort of 214 patients diagnosed with multiple myeloma in France before the age of 40.¹ The study describes baseline disease characteristics and prognostic factors of overall survival in these patients.

In the United States, the average age at diagnosis with multiple myeloma is 69 years, and ∼95% of newly diagnosed patients are ≥50 years.² Because of this demographic, there is only limited information on the biology and clinical management of younger individuals. It is estimated that there will be ∼35 000 new cases of multiple myeloma in 2021; ∼1500 to 2000 of those cases will be in patients in their 30s and 40s.² Unfortunately, there is no established cure for multiple myeloma; however, access to modern and effective drugs has translated into a significantly improved overall survival for patients with multiple myeloma. Indeed, an otherwise healthy younger individual diagnosed with multiple myeloma has a projected average overall survival of ≥10 years.² Overall survival will likely be even greater assuming that many new drugs will be developed during this timeframe. Altogether, these factors contribute to a rising prevalence in the general population of the number of patients living with multiple myeloma. Indeed, >150 000 individuals are currently living with multiple myeloma in the United States. Although no official statistics are available, it seems reasonable to estimate that 10 000 to 20 000 of those individuals are in their 30s and 40s. When multiplying the number of patients with long overall survival (median overall survival ≥10-20 years), the number of person-years is substantial. Despite these facts, limited attention has been paid to this group of patients.

In the study by Caulier et al, the median patient age was 37 years (range 18-40), and 64% were men. When comparing baseline characteristics to older patients, consistent with previously reported smaller cohorts,^3,4 the authors found that almost half of the patients diagnosed before age 40 had low-risk disease (International Staging System, stage 1), which is in sharp contrast to older patients.^1,5 The authors speculate that this finding likely contributed to the greater overall survival (median 14.5 years) and the observed 84% 5-year overall survival rate. The lower rate of comorbidities and the greater ability to tolerate treatment side effects also likely contributed to a better overall survival of younger patients.

Furthermore, Caulier et al did address limitations of the current retrospective study. For example, the impact of contemporary drug regimens and immunotherapies on overall survival is unclear. The study is retrospective, covering patients diagnosed from 1 January 2000, to 31 December 2015, and was not extracted exclusively from randomized clinical trials. Consequently, data-driven claims on optimal treatments and sequence of therapies in these patients are not possible. The authors also state that emerging immunotherapies, including new anti-CD38 antibodies such as isatuximab, anti-SLAMF7, and anti-BCMA antibodies and bi-specific antibodies, are promising and may further improve treatment outcomes of multiple myeloma in very young patients.^6-9 Finally, a limitation is the lack of data on race and ethnicity, which are especially important. For example, on average, the median age of diagnosis with multiple myeloma among African American patients is ∼10 years younger than White patients because of earlier disease onset; African Americans also have ∼10 years earlier age of onset for monoclonal gammopathy of undetermined significance.¹⁰ 

The current study is important in many ways. Although the average age of onset for multiple myeloma is close to 70 years, the study emphasizes the fact that multiple myeloma can present at younger ages. These patients have significantly different life challenges compared with older patients. Based on experience from our own clinics, for example, younger patients with multiple myeloma face different hurdles such as childcare, pregnancy, career challenges, and other life circumstances that cause additional stress. There is need for more research focusing on younger patients with multiple myeloma and their needs, including clinical management, exploration of differences in disease biology, social support, drug development, and long-term follow-up of therapies.