Supportive Care Strategies in Myelodysplastic Syndromes and Acute Myeloid Leukemia in Older Adults: A National Survey of Canadian Hematologists

BACKGROUND: Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) represent a spectrum of severe myeloid disorders characterized by marrow failure, cytopenias, and complications related to bleeding and infection. Due to patient and disease factors, many patients are treated with less-intensive therapy, such as transfusion support, erythropoietin stimulating agents, luspatercept, lenalidomide and hypomethylating agents. However, optimal supportive care strategies to minimize bleeding and infectious complications among older adults receiving less intensive therapy have not been systematically evaluated.

OBJECTIVES: The objectives of the survey were to: a) evaluate self-reported use of tranexamic acid (TXA) and antimicrobial prophylaxis; b) identify perceived barriers and facilitators to the use of TXA and antimicrobial prophylaxis; c) characterize the degree of uncertainty regarding the benefits and harms of TXA and prophylactic antimicrobials in this patient population; and d) assess physician interest in future clinical trials of TXA and/or prophylactic antimicrobials.

METHODS: We conducted a national cross-sectional survey of Canadian hematologists to explore current practice variation regarding the use of TXA and prophylactic antimicrobials in patients with MDS and AML treated with less intensive therapy, and evaluate equipoise for future trials. Survey items were generated iteratively through a combination of literature review and discussion with content experts until thematic saturation was achieved. The questionnaire was pilot-tested by collaborators prior to dissemination to assess the required completion time and provide feedback on flow, clarity, redundancy and comprehensiveness. The electronic platform REDCap was used to create and disseminate the survey tool. The survey was distributed to all hematologists affiliated with a Canadian university, representing both key knowledge users and potential participants in an investigative network for future clinical trials.

RESULTS: The survey response rate was 52% (159/304 invited participants). Of the 159 hematologists, 105 indicated that they treated MDS/AML patients with less intensive therapy and responded to the further questions about this patient population. Most (97/105; 92%) hematologists worked in an academic/tertiary care setting; 8% (n=8/105) worked in a community setting. Prophylactic TXA was used by 57% (n=60/105) of hematologists; the most frequent reason for not using TXA was uncertainty about the benefits or harms. Nearly all (95%; 100/105) hematologists agreed that a trial of TXA is needed (n=78), or potentially needed (n=22). Use of prophylactic antimicrobials varied by the chemotherapy treatment regimen. The most frequently prescribed antibacterials were fluroquinolones (36% of respondents; n=38), trimethoprim/sulfamethoxazole (9%; n=9), and amoxicillin-clavulanate (5%; n=5). The most commonly used antifungals were fluconazole (35% of respondents; n=37) and voriconazole (19%; n=20). Valacyclovir (29% of respondents; n=30) and acyclovir (15%; n=16) were the antivirals prescribed. The most common reason for not using prophylactic antimicrobials was an insufficient level of evidence (70%; n=73). The majority (78%, n=82) of respondents agreed that a trial is needed to evaluate optimal antimicrobial prophylaxis in this at-risk patient population.

CONCLUSIONS: Among survey respondents, there was variation in the use of supportive case strategies to address bleeding and infection risk in older adults with MDS/AML. Most hematologists who treat MDS/AML with less intensive therapy felt that clinical trials are needed to define the use of TXA and prophylactic antimicrobials in this patient population.

Mozessohn:Abbvie: Current holder of stock options in a privately-held company; Bristol Myers Squibb: Current holder of stock options in a privately-held company; Johnson & Johnson: Current holder of stock options in a privately-held company; Merck and Co: Current holder of stock options in a privately-held company; Novo Nordisk: Current holder of stock options in a privately-held company. Sanford:Astellas: Other: Advisory Board ; Pfizer: Research Funding; Abbvie: Other: Advisory Board . Hay:AbbVie: Research Funding; Roche: Research Funding; Karyopharm: Research Funding; Merck: Research Funding; Seagen: Research Funding. Buckstein:Taiho: Honoraria, Research Funding; Takeda: Research Funding; BMS: Honoraria, Research Funding.