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Personalizing therapy for older adults with acute myeloid leukemia: Role of geriatric assessment and genetic profiling.

ABSTRACT: Acute myeloid leukemia (AML) presents therapeutic challenges in older adults because of high-risk leukemia biology conferring chemoresistance, and poor functional status resulting in increased therapy-related toxicities. Recent FDA approval of 8 new drugs for AML has increased therapeutic armamentarium and also provides effective low-intensity treatment options. Rational therapy selection strategies that consider individual's risk of therapy-related toxicities and probability of disease control can maximize benefits of available treatments. Studies have demonstrated that fitness level, measured by geriatric assessment can predict therapy-related toxicities, whereas cytogenetic and mutation results correlate with the probability of responses to standard chemotherapy. We are approaching an era when we move from "one size fits all" approach to personalized therapy selection based on geriatric assessment, genetic and molecular profiling.

SUBMITTER: Bhatt VR

PROVIDER: S-EPMC6481658 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Personalizing therapy for older adults with acute myeloid leukemia: Role of geriatric assessment and genetic profiling.

Bhatt Vijaya Raj VR

Cancer treatment reviews 20190411

Acute myeloid leukemia (AML) presents therapeutic challenges in older adults because of high-risk leukemia biology conferring chemoresistance, and poor functional status resulting in increased therapy-related toxicities. Recent FDA approval of 8 new drugs for AML has increased therapeutic armamentarium and also provides effective low-intensity treatment options. Rational therapy selection strategies that consider individual's risk of therapy-related toxicities and probability of disease control ...[more]

PMID: 31003190

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Integrating geriatric assessment and genetic profiling to personalize therapy selection in older adults with acute myeloid leukemia.

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Project description: Not available

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Project description:Background and objectivesNovel, non-cytotoxic agents are driving a paradigm shift for treatment of older adults with acute myeloid leukemia (AML). Older patients who initially receive intensive cytotoxic induction may choose to not proceed with cytotoxic consolidation therapy. Lenalidomide is an orally-administered immunomodulatory small molecule with activity in AML and a favorable safety profile in older adults with active leukemia. We conducted a phase Ib study of lenalidomide as post-remission therapy in older adults and assessed its impact on geriatric functional domains.Materials and methodsParticipants were patients with AML over age 60 years who had undergone induction therapy and were poor candidates for cytotoxic consolidation. Lenalidomide was administered for 28 days in three dose cohorts. A Bayesian dose-escalation method determined cohort assignment and maximum tolerated dose (MTD). Geriatric assessment (GA) was performed before and after the cycle of lenalidomide.ResultsNineteen patients with median age 68 were treated with at least one 28-day course of lenalidomide. Dose-limiting toxicities were observed in three participants at 25 mg, zero participants at 35 mg, and one participant at 50 mg. MTD was 35 mg. Median relapse-free survival was 4.3 months. GA was completed before and after treatment in fifteen patients, demonstrating improved cognitive function and no changes in physical, psychological, or social function after lenalidomide.ConclusionLenalidomide can be safely administered to older adults with AML with preservation of functional domains important to older patients. Serial GA can be performed in a novel drug study as a tool to characterize treatment tolerability.

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Project description: Not available

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