e19072 Background: This study aimed to provide a comprehensive overview of the evidence available on drug-induced myelosuppression in patients with MDS or AML. Methods: A systematic literature review (SLR) was conducted using MEDLINE, Embase, and Cochrane to identify studies published 2002-2022 explicitly targeting drug-induced myelosuppression with current and emerging treatments used for MDS and/or AML (venetoclax [VEN], azacitidine [AZA], magrolimab, sabatolimab, decitabine [DEC], cedazuridine, lenalidomide [LEN], low-dose cytarabine [LDAC], intensive chemotherapy [IC]) in terms of drug-induced AEs, treatment discontinuation, QOL, and MRU. Article selection was based on predefined eligibility criteria (PICO+ framework), with a focus on specific geographic regions (USA, UK, Spain, Italy, France, Germany). Results: A total of 48 studies reporting on VEN, AZA, DEC, LEN, LDAC, and IC based regimens met the inclusion criteria. In MDS populations, myelotoxicity was reported in all blood cell lineages in association with AZA, DEC, and LEN monotherapies. In AML populations, myelosuppression was reported in all blood cell lineages in association with all regimens except LEN. In general, the reported incidence of myelosuppressive AEs was higher in studies published prior to 2010 and in studies of patients with AML or MDS who had received prior treatments vs more recent studies (2018-2022) and studies of treatment-naive patients, respectively. Differences observed between the two time periods might be explained by improved supportive care (AEs prophylaxis and management). In treatment-naive AML populations, the incidence of any-grade febrile neutropenia, leukopenia, and anemia was up to 3-fold higher with AZA combination therapy vs monotherapy, and the incidence of any-grade neutropenia and febrile neutropenia was 2-fold higher with LDAC combination regimens vs monotherapy, suggestive of an additive effect. The most common reasons for treatment discontinuation were AEs and disease progression. QOL significantly improved with AZA monotherapy; however, hematologic improvement was not explicitly mentioned as the main driver. There were no data on combination therapies to indicate whether the improvement in QOL compensated for the added drug-induced AEs. The few studies that reported on the impact of myelosuppression on MRU did not provide conclusive results. Conclusions: This SLR suggests that combining ≥2 myelosuppressive drugs may result in increased toxicity; however, the lack of evidence on the impact of myelotoxicity on QOL and MRU with ≥2 myelosuppressive drugs limits informed decision-making in routine clinical practice. Further research is needed to explore the impact of drug-induced myelosuppression in patients with MDS or AML.

Background: Although novel disease-modifying treatments for higher-risk myelodysplastic syndromes (HR-MDS) are emerging, current treatment options forpatients with HR-MDS are limited. This study sought to explore patients', caregivers', and hematology and oncology providers' perspectives on and experiences with patient-provider communication and its role in the diagnostic and treatment process in patients with HR-MDS. Methods: Qualitative, semi-structured interviews with patients with HR-MDS, caregivers to patients with HR-MDS, and board-certified oncologists and/or hematologists managing patients with HR-MDS in the United States. Participants were recruited through the MDS Foundation constituency and through a survey vendor partner. Thematic analysis was used to identify key factors associated with the role and impact of communication between patients, caregivers, and providers. Results: Eight patients (mean age = 68.1 years, 50% male, 88% White, 88% suburban), 6 caregivers (mean age = 64.3 years, 83% female, 100% White, 83% suburban), and 18 providers (mean age = 52.6 years, 78% male, 67% >10 years of clinical practice, 50% urban, 61% treated >10 patients with HR-MDS in past year) participated in the study. During the diagnostic workup phase, patients and caregivers described communication as limited and stated that they had not been provided with adequate information or educational resources about HR-MDS that could inform decision-making. They reported a significant lack of knowledge about the condition, their prognosis, and available treatment options. Lack of provider communication and inadequate education about HR-MDS was also viewed as a treatment barrier itself, in addition to treatment access, logistical barriers, and lack of support by a caregiver. Some patients and caregivers felt that without adequate knowledge about HR-MDS, they could not ask appropriate questions, while others reported being content with “not knowing” and relying solely on provider recommendations. Having additional education around HR-MDS was viewed as allowing patients to better articulate their preferences during treatment decision-making. Conversely, providers in the study reported consistently accounting for patient preferences when making treatment recommendations. Providers reported tailoring their communication approach to each patient and seeking equipoise when needing to adequately explain the seriousness of the condition without instilling panic or diminishing hope. However, they also noted variability in willingness to engage in decision-making among their patients with HR-MDS, attributing active participation mediated by patient age, education and health literacy level, and cultural background. Providers described struggling with making treatment recommendations (due to a current lack of effective treatment options) for their patients with HR-MDS as the most significant treatment barrier, further compounded by challenges in explaining the nuances of HR-MDS treatment to patients. Strong and continuous communication between the patient, caregiver, and clinical care team, along with the availability of resources to facilitate timely communication and education, such as telehealth options and patient portals, were viewed as facilitators by patients and caregivers. Providers noted that nurse navigators, social workers, patient assistance programs, patient advocates, and educational materials were key facilitators in improving patient-provider decision-making and patient outcomes. Conclusion: While strong patient-provider communication is desired by patients, caregivers, and providers, and can be a catalyst for educated treatment preferences, uncertainty exists around how to best involve patients in HR-MDS treatment decisions. When patients present with lower health literacy, lack of desire to be involved in decision-making, or a preference for a provider-guided decision, providers struggle to find the right balance of education and information provision. As novel therapies emerge and treatment options expand for patients with HR-MDS, it is imperative to further develop and evaluate educational materials for patients with HR-MDS delivered via novel technological methods, facilitate the use of telehealth and patient portals, and ensure patient navigation of resources to support patient-provider communication.

Topic: 10. Myelodysplastic syndromes - Clinical Background: Adverse events (AEs) associated with drug-induced myelosuppression are of substantial concern when treating patients with hematologic malignancies, especially with combination therapies. Aims: This study aimed to provide a comprehensive overview of the evidence available on drug-induced myelosuppression in patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML). Methods: A systematic literature review (SLR) was conducted using MEDLINE, Embase, and Cochrane to identify studies published in 2002-2022, explicitly targeting drug-induced myelosuppression with current and emerging treatments for MDS and/or AML (venetoclax [VEN], azacitidine [AZA], magrolimab, sabatolimab, decitabine [DEC], cedazuridine, lenalidomide [LEN], low-dose cytarabine [LDAC], intensive chemotherapy [IC]) in terms of drug-induced AEs, treatment discontinuation, quality of life (QOL), and medical resource use (MRU). Articles were selected based on predefined eligibility criteria (PICO+ framework), with a focus on specific countries (US, UK, Spain, Italy, France, Germany). Results: A total of 48 studies reporting on VEN-, AZA-, DEC-, LEN-, LDAC-, and IC-based regimens met the inclusion criteria. In MDS populations, myelotoxicity associated with AZA, DEC, and LEN monotherapies was reported in all blood cell lineages. In AML populations, myelosuppression associated with all regimens except LEN was reported in all blood cell lineages. In general, the reported incidence of myelosuppressive AEs was higher in studies published prior to 2010 vs more recently (2018-2022) and in studies in patients with AML or MDS who had received prior treatment vs treatment-naive patients. Differences between the two time periods might be explained by improved supportive care (AE prophylaxis and management). In treatment-naive AML populations, the incidence of any-grade febrile neutropenia, leukopenia, and anemia was up to 3-fold higher with AZA combination therapy vs monotherapy, and the incidence of any-grade neutropenia and febrile neutropenia was 2-fold higher with LDAC combination regimens vs monotherapy, suggesting an additive effect. The most common reasons for treatment discontinuation were AEs and disease progression. QOL was significantly improved with AZA monotherapy; however, hematologic improvement was not explicitly mentioned as the main driver. There were no data on combination therapies to indicate whether the improvement in QOL compensated for the added drug-induced AEs. The few studies that reported on the impact of myelosuppression on MRU did not provide conclusive results. Summary/Conclusion: This SLR suggests that combining ≥2 myelosuppressive drugs may result in increased toxicity; however, the lack of evidence on the impact of myelotoxicity on QOL and MRU with ≥2 myelosuppressive drugs limits informed decision-making in routine clinical practice. Further research is needed to explore the impact of drug-induced myelosuppression in patients with MDS or AML. Keywords: Systematic review, MDS/AML, Myelosuppression