INTRODUCTION
The risk of treatment-related acute myeloid leukemia (t-AML) in adolescents and young adults (AYA) with first cancers treated with chemotherapy with or without radiation is not well characterized. We analyzed Surveillance, Epidemiology and End Result (SEER) data for the past 45-years (1975-2020) to identify the overall risk of t-AML in treated AYA cancer patients (pts) and by index cancer sites as well as latency periods.
METHOD
We analyzed NCI's SEER-8 registries. ICD-O-3/WHO-2008 codes were used to identify pts with index cancer types between the ages of 15-39 years (AYA), treated with either chemotherapy or radiotherapy, and with a subsequent diagnosis of acute myeloid leukemia (AML) at least one year after index cancer, between January 1975 and December 2020. The risk of t-AML was estimated by standardized incidence ratio (SIR), defined as the ratio of observed t-AML-cases in the AYA-with-cancer, to the expected number of AML-cases in the matched general US population. A reference rate file for AML incidence in age, gender, race and calendar-year matched US population is available in SEERStat software. A Poisson distribution of observed t-AML was assumed for the calculation of 95% confidence intervals (CIs). A P-value <.05 was considered statistically significant. We stratified the risk of t-AML for index cancer types with ten or more pts, by attained-calendar-years, and latency at multiple time intervals (Table-1) from index cancer diagnosis.
RESULT
Among 102,879 AYA cancer pts eligible for analysis, 236 pts developed t-AML with SIR of 6.19 (95%CI: 5.43-7.04, P <.05) with excess risk of 1.46 per-10000 person-years (pyrs). (Table-1). We stratified risk for index cancer types with at least ten patients developing t-AML, these included breast, Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), testicular, thyroid, bone and joint, and soft tissue including heart. As a general trend, risk of t-AML was highest during 1-3 years after index cancer diagnosis compared to subsequent latency periods. However, risk for t-AML was significantly greater than the matched-general US population even after 20-40 years of breast cancer, HL, and NHL (Table-1).
When stratified by attained calendar-year periods (1975-1985, 1986-1995, 1996-2005, 2006-2015, 2016-2020), risk for t-AML was higher than general population in all time periods. However, overall SIR was comparatively lower for recent time periods, particularly lowest during 2016-2020 [SIR: 3.49 (2.51-4.72, P <.05)]. Notably, the highest risk for t-AML in 2016-2020 was observed with index cancer of soft tissue including heart [SIR: 10.12 (1.23-36.57), P <.05].
CONCLUSION
In this study spanning between 1975-2020, we observed the risk of t-AML trending down among AYA in recent years, albeit higher than the age matched general population. The risk of t-AML remained significantly elevated even after 20-40 from diagnosis of breast cancer, HL and NHL. Since these pts likely received radiation and older (higher intensity) chemotherapy based-regimens, it is essential to analyze the long-term impact of newer therapies for these cancers and assess the risk of t-AML in future studies.
Disclosures
Singh:Rigel: Other: Advisor or review panel participant. Advani:OBI: Research Funding; Incyte: Research Funding; Kite: Honoraria, Other: consulting, Research Funding; Immunogen: Research Funding; Glycomimetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Research Funding; Macrogenics: Research Funding; Servier: Research Funding; Kura: Honoraria; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees; Beam: Honoraria; Taiho: Honoraria, Membership on an entity's Board of Directors or advisory committees; Nkarta: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Research Funding; Amgen: Honoraria, Other: advisory board, Research Funding. Carraway:AbbVie: Other; Agios: Consultancy, Speakers Bureau; Celgene: Research Funding; Daiichi: Consultancy; Genentech: Consultancy; Stemline Therapeutics: Consultancy, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Other: Travel, Accommodations, Expenses , Speakers Bureau; BMS: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Other: Travel, Accommodations, Expenses , Speakers Bureau; Astex Pharmaceuticals: Other; Syndax: Other: DSMB; Takeda: Other. Gerds:Accurate Pharmaceuticals, Constellation Pharmaceuticals, CTI BioPharma, Imago BioSciences, Incyte Corporation, Kratos Pharmaceuticals: Research Funding; AbbVie, Bristol Myers Squibb, Constellation Pharmaceuticals, GlaxoSmithKline, Kartos, Novartis, PharmaEssentia, Sierra Oncology: Consultancy. Mukherjee:Genentech and AbbVie: Other: Advisory Board; Aplastic Anemia and MDS International Foundation: Honoraria; Novartis: Other: Advisory Board; Blueprint Medicines Corporation: Other: Advisory Board; Bristol Myers Squibb: Other: Advisory Board; Bristol Myers Squibb: Honoraria; Celgene/Acceleron: Other: Advisory Board; Celgene (now BMS): Honoraria; EUSA: Other: Advisory Board; EUSA: Honoraria; McGraw Hill Hematology Oncology Board Review: Honoraria; BioPharm: Consultancy; Celgene (now BMS): Consultancy; Novartis: Consultancy; Bristol Myers Squibb: Consultancy; Celgene (now BMS): Research Funding; Novartis: Research Funding; Jazz Pharmaceuticals: Research Funding.
