Despite Treatment Improvements, Second Primary Malignancies Adversely Affect MM Prognosis

A study published in the American Journal of Hematology found that second primary malignancies (SPMs) adversely affect survival outcomes for patients with multiple myeloma (MM), despite improvements in MM treatments and outcomes in the modern era.

Previous research on SPM development and mortality has largely been conducted either in European countries with different racial and ethnic diversity compared with the United States, have been retrospective single-center studies, or were done prior to the modern era of cancer therapy options and International Myeloma Working Group imaging guidelines.

“As novel MM therapies translate into improved long-term outcomes, it is conceivable that extended survival will lead to more time to develop SPMs,” the authors wrote. “Although there is significant literature regarding the incidence of SPMs in MM, there is a relative paucity of data regarding prognosis and mortality after SPM development.”

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The new study focused on outcomes for patients with MM who developed SPMs in the modern era using aggregated, de-identified, patient-level data from the American Society of Clinical Oncology's (ASCO) CancerLinQ Discovery (CLQD) MM data set. The CLQD was created and implemented by ASCO and includes data from diverse practice settings in the United States, and the current analysis included data from 51,105 patients diagnosed with MM between 2009 and 2021.

SPMs were defined as malignancies diagnosed a minimum of 30 days after MM diagnosis and that did not include the term “secondary,” as this would encompass metastatic lesions rather than new primary cancer diagnoses. The SPMs were identified through ICD-9 and ICD-10 codes and were stratified by when they occurred: synchronous SPMs were those that occurred within 6 months of MM diagnosis, and metachronous SPMs occurred at least 6 months after MM diagnosis.

The main end point was overall survival (OS) among patients with MM who developed SPMs, with OS calculated from both the date of MM diagnosis and the date of SPM diagnosis.

Median follow-up was 22 months (range, 0-151), and 8.2% of patients (n = 4188) were diagnosed with SPMs. The median time from MM to SPM diagnosis was 15 months (range, 1-145 months), and the majority (72%) of SPMs were metachronous, and each individual SPM reflected this overall trend. The most commonly occurring SPMs were:

• basal cell and squamous cell carcinomas (1.6%, n = 826)
• breast cancer (1.3%, n = 684)
• non-Hodgkin lymphoma (NHL, 1.3%, n = 667)
• prostate cancer (1%, n = 510)
• acute myeloid leukemia (AML, 1%, n = 485)
• lung cancer (0.9%, n = 468)
• melanoma (0.8%, n = 425)
• colorectal cancer (0.6%, n = 320)
• diffuse large B-cell lymphoma (DLBCL, 0.4%, n = 203)
• acute lymphoblastic leukemia (ALL, 0.3%, n = 174)

Former or current smokers were more likely to be diagnosed with SPMs vs nonsmokers (risk ratio [RR], 1.49; 95% CI, 1.38-1.60; P < .001). Patients who received melphalan, a proxy measure for autologous stem-cell transplantation, showed an increased risk of AML development (RR, 1.58; 95% CI, 1.06-2.33; P = .023).

The median OS from MM diagnosis was 107 months in the overall cohort, and SPMs were associated with worse OS (HR 1.30; 95% CI, 1.18-1.43; P < .001). Synchronous and metachronous SPMs were both associated with shorter OS ([HR 1.47; 95% CI, 1.23-1.75; P < .001] and [HR 1.25; 95% CI, 1.12-1.40; P < .001], respectively).

The SPMs that were found impactful in terms of OS were:

• AML (HR, 2.58; 95% CI, 2.00-3.32; P < .001)
• ALL (HR, 2.31; 95% CI, 1.49-3.55; P < .001)
• lung cancer (HR 2.27; 95% CI, 1.73-2.96; P < .001)
• colorectal cancer (HR 2.10; 95% CI, 1.48-2.99; P < .001)
• DLBCL (HR 1.63; 95% CI, 1.04-2.57; P = .035)
• melanoma (HR 1.41; 95% CI, 1.07-1.85; P = .015)

Synchronous lung cancer, synchronous AML, metachronous AML, metachronous colorectal cancer, and metachronous lung cancer were associated with the worse OS outcomes when SPMs were stratified by the time frame when they occurred.

“While retrospective designs have their limitations, some observations in this study are on par with what is reported in the literature, serving as a good internal control, and validating the accuracy of the CLQD MM data,” the authors wrote. The incidence of SPMs was consistent with past research, and the median OS of 107 months was consistent with long-term survival reports in newly diagnosed MM receiving induction therapy, they added.

The authors concluded by emphasizing that a better understanding of causes of death among patients who develop SPMs after initial MM diagnosis could help clinicians determine the risks of death associated with SPMs and MM and would help inform treatment decisions.

Reference

Gibson SJ, Cooper JD, Pham K, Sunderland K, Thornton JA, DeStefano CB. Prognostic impact of second primary malignancies in multiple myeloma: An ASCO CancerLinQ discovery analysis of the modern era. AM J Hematol. Published online August 30, 2023. doi:10.1002/ajh.27066