Young Myeloma Patients: A Forgotten Subgroup?

About every summary of multiple myeloma clinical studies published reminds us that our fellow patients tend to be around 70 years old. Rarely do we see a comment that about 10% of myeloma patients are ≤ 50 years.

This is not an insignificant patient segment. For example, in the United States there are + 10,000 fellow patients who fit into this category. An interesting paper published in the journal Current Oncology summarizes the efforts of a Canadian group of researchers to understand better the “characteristics at diagnosis, cytogenetics, treatments, and outcomes” of young(er) patients who are underrepresented in myeloma research and literature.

This Canadian team completed an exhaustive literature review of studies published during the period between January 2010 through the end of December 2022 involving these “young patients”. This period captures patients treated with  “novel treatments” as well as data on disease risk stratification using the more recent prognostic scores. The team started with a set of 226 studies but only ended up with 16 studies that provided adequate information about younger patients, and of this last set, only 11 studies included cytogenetic information. 

At the onset, the above-referenced paper puts the topic of myeloma in young people in a very succinct and relevant perspective :

“The average years of life lost per patient is as high as 36 years for patients under 40 years and reaches up to 27 years for patients between the ages of 40 to 49 years. In contrast, the entire myeloma population loses 16.8 years of life on average to the disease. In addition to a significantly shorter life expectancy, young patients are affected in their most productive years professionally and suffer a significant deterioration in their quality of life due to the disease.”

The authors of the study report the following results :

Disease Characteristics at Diagnosis 

• “The incidence of light chain disease is approximately 15% in the general myeloma population, studies including only young patients have reported incidences ranging from 19 to 45% in patients ≤ 50 years.”
• “Approximately 25% of all multiple myelomas are in the ISS 1 subgroup [16,24]. In some studies, without an older age group comparator included in this review, a higher proportion of ISS 1 was reported, ranging from 32 to 68%.” In other words, younger patients seem to have less severe disease.
• “It remains unclear whether young patients diagnosed with myeloma have an increased incidence of a familial history of myeloma or secondary hematological malignancies.”

Cytogenetics

There are significant differences in the abnormalities tested and reported in the literature. Several studies reported similar cytogenetics for younger and older patients. Others reported a 3 to 4 times higher prevalence of t(11;14) in younger patients, a 2x higher prevalence of (del (17p) and t(4;14)) in patients aged 21-40 years vs. 41-60 years, a 2.5x higher incidence del (17p) in patients < 40 compared to the entire myeloma cohort.

On a personal note: I find these higher incidences of high/higher risk cytogenetics somewhat at variance with the earlier conclusion that younger patients tend to present with less severe disease. 

Treatments and Outcomes

Quite a wide range of treatments was reported in the 16 studies reviewed in detail, making it difficult to come to well-defined conclusions.

In the authors' words, “Patients included were treated over a span of several years, drugs used for induction were reported inconsistently, and older regimens were of common occurrence. Studies reporting induction treatments with a combination of a proteasome inhibitor (PI) and an immunomodulatory drug (IMID) ranged from 15 to 69% in young patients. Autologous stem cell transplant (ASCT), currently considered a standard of care in young patients, was performed heterogeneously. Allogeneic [stem cell transplant] was seldom used. Median [overall survival], reported in 4 studies, ranged from 61 to 175 months. In studies with a comparator, all studies reported a longer 5-year [overall survival] in young patients.”

The authors conclude :

• “Whether multiple myeloma of the young is a different disease entity remains unclear and a matter of debate.”
• “The specific chromosomal aberrations in young patients are crucial since they can reflect tumor evolution and response to certain therapies. Interphase fluorescence in situ hybridization (iFISH) is the technique of choice for cytogenetic analysis. More advanced techniques such as next-generation sequencing (NGS) should also aid in our understanding.”
• “Besides del (17p) deletion, t(4;14), and t(14;16), young patients should also be screened for other cytogenetic abnormalities associated with high-risk disease, such as t(14;20) and chromosome 1 abnormalities."
• “At the present time, it remains unclear whether young myeloma patients are more prone to have high-risk cytogenetics for several reasons.”
• “Young patients should be enrolled in clinical trials, and specific stratification of different age groups should be conducted to further understand the characteristics and outcomes of their disease.”
• “These [younger] patients are diagnosed during their most productive years of life and suffer from significantly higher personal, familial, professional, and economic burdens compared to older patients, urging the need for tailored treatment approaches.”
• “Survivorship of young patients with multiple myeloma deserves particular attention given their long disease journey with multiple potential complications, including secondary malignancies.”
• “Further studies will elucidate if innovative cellular therapies such as upfront CAR-T cells or other novel cellular therapies could be beneficial in this population.”

For a 1:1 connection with a (young) Coach who understands what you are experiencing, sign up here: HealthTree Myeloma Coach 

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