# Characteristics and Outcomes of Second Primary Multiple Myeloma in Adult Cancer Survivors: A Population‐Based Cohort Study

## TL;DR

This study finds that second primary multiple myeloma in cancer survivors has different characteristics and outcomes compared to first cases, influenced by prior cancers and their treatments.

## Contribution

The study identifies specific prior cancers and treatments that influence survival outcomes in second primary multiple myeloma patients.

## Key findings

- Second primary multiple myeloma patients had higher male representation, older age, and higher White race proportion compared to first primary cases.
- Certain prior cancers like lymphoma and melanoma showed protective effects on multiple myeloma-specific mortality.
- Chemotherapy for prior lymphoma increased all-cause mortality risk, while radiotherapy for breast cancer and surgery for prostate cancer reduced it.

## Abstract

This study aimed to investigate characteristics and outcomes of second primary multiple myeloma (2‐MM) stratified by prior primary malignancies (PPMs), and further explore the effect of PPM treatment modalities on multiple myeloma (MM) prognosis in the United States (US) population.

The retrospective study was analyzed based on MM patients in the Surveillance, Epidemiology, and End Results (SEER) database (2000–2021). Patients with 2‐MM, defined as MM diagnosed ≥ 6 months after a PPM, were stratified into 25 subgroups based on PPM categories. Univariable and multivariable competing risk regression models were constructed to estimate MM‐specific mortality. The Kaplan–Meier method and a multivariable Cox regression model were conducted to analyze all‐cause mortality.

We identified 74,932 patients with first primary multiple myeloma (1‐MM) and 6465 patients with 2‐MM. Compared to the 1‐MM cohort, the 2‐MM cohort exhibited a higher proportion of males, older age at diagnosis, and greater representation of the White race. The multivariable analysis demonstrated a reduced risk of MM‐specific mortality in 2‐MM against 1‐MM. PPMs of soft tissue (including heart), melanoma of the skin, corpus uteri, prostate, kidney and renal pelvis, and lymphoma, showed protective effects on MM‐specific mortality in 2‐MM. Notably, many PPMs that developed into 2‐MM exhibited elevated all‐cause mortality risks in multivariable analysis. Additionally, chemotherapy for prior lymphoma was associated with an increased all‐cause mortality risk in 2‐MM patients, whereas, radiotherapy for prior breast cancer and surgery for prior prostate cancer were linked to a decreased risk.

Compared to 1‐MM, 2‐MM exhibited distinct characteristics and survival outcomes in adults, which were associated with PPM types and their treatment modalities. These findings provide critical insights for risk stratification and survivorship care in US adults.

By leveraging SEER registry data (2000–2021) with rigorous competing risk analysis, we found that second primary multiple myeloma, considered as a vital prognostic factor, exhibited distinct characteristics and survival outcomes compared to first primary multiple myeloma in US adults, which were associated with prior primary malignancy types and their treatment modalities.