BETHESDA, MD—Multiple myeloma (MM) is primarily a disease of the elderly, with an average age at diagnosis of 68. Still, adolescents and young adults (AYAs) do develop the blood disease and represent about 5% of all new cases.
Because MM is so uncommon in younger age groups, little research has been conducted to guide the treatment of AYAs. Consequently, their care is often derived from therapies and procedures created with much older and often sicker adults in mind.
Autologous stem cell transplant (ASCT) remains the preferred potentially curative treatment for fit patients with MM following treatment with alkylating agents such as melphalan. Whether ASCT is the best course for young patients, who have higher risk of germline cancer predisposition than their elders and also typically live up to 15 years longer, thanks to advances in care and better overall health, is unclear.
The longer life span, while obviously a benefit, creates a challenge in treatment decisions, because patients with MM have an elevated risk of developing secondary primary malignancies (SPMs), even without the mutations common in adolescents and young adults diagnosed with MM. Researchers at the Walter Reed Military Medical Center (WRMMC) in Bethesda, MD, and the David Grant USAF Medical Center in Fairfield, CA., turned to the CancerLinQ registry created by the American Society of Clinical Oncology to evaluate the incidence of SPMs in patients with MM and compare outcomes between those under age 45 and those older than that.1
The team retrospectively analyzed records of 34,234 patients diagnosed with MM between 2009 and 2021 in more than 100 U.S. oncology clinics and hospitals and identified 1,173 who were adolescents or young adults. Across all patients in the study population, the most common SPMs were chronic lymphocytic leukemia, acute lymphoblastic lymphoma, acute myeloid leukemia, breast cancer, colorectal cancer, diffuse large B cell lymphoma, non-melanoma skin cancer, lung cancer, melanoma, non-Hodgkin lymphoma, and prostate cancer.
For MM patients younger than age 45, the risk of developing one of these SPMs was 9.12%, while for those 45 and older, the risk was a comparable 10.67%.
In a presentation at the 64th American Society of Hematology Annual Meeting in New Orleans on Dec. 11, however, Steven J. Gibson, MD, of WRMMC, pointed out that the incidence rates were not as similar as they might seem.
Younger patients were almost four times more likely to develop acute lymphocytic leukemia (RR 3.7, p<0.001, 95% CI 2.35-5.93) and almost twice as likely to be diagnosed with acute myeloid leukemia following their MM diagnosis. They also had a 50% higher risk of non-Hodgkin lymphoma (RR 1.5, p=0.03, 95% CI 1.03-2.04). On the flip side, they were less likely to develop basal cell or squamous cell carcinoma or prostate cancer than older patients and had about the same risk of developing breast cancer, colorectal cancer, chronic lymphocytic leukemia, lung cancer, melanoma or diffuse large B cell lymphoma.
In short, while the overall risk of secondary primary malignancies appear similar between young and older patients with MM, adolescents and young adults are much more likely to develop hematologic malignancies. Further, young patients have an 80% higher risk of developing acute myeloid leukemia, which has a significant negative impact on survival.
One factor that contributes to AML in patient with MM is use of melphalan conditioning as part of ASCT treatment. As advances in treatment options erode the survival benefit of ASCT and may have eliminated the advantage entirely in younger patients, “this finding highlights the increased risk of AML in AYA MM patients and suggests that perhaps up-front ASCT could be deferred in this specific population,” the team said. “Despite having SPMs, AYA MM patients had an excellent prognosis, with median long-term survival not reached.”
- Gibson SJ, Cooper JD, Thornton JA, Pham K, Sunderland K, DeStefano CB. Survival of Patients with Multiple Myeloma Diagnosed with Second Primary Malignancies: An ASCO Cancerlinq Analysis. Abstract 3189. 2022 ASH Annual Meeting. Dec. 11, 2022.
