Patient Preferences for Benefits, Risks, and Administration Route of Hypomethylating Agents in Myelodysplastic Syndromes

Zeidan, Amer M.; Tsai, Jui-Hua; Karimi, Milad; Schmier, Jordana K.; Jayade, Sayeli; Zormpas, Evangelos; Hassan, Audrey; Ruiters, Desiree; Anthony, Cindy; Hill, Kala; Wert, Tim; Botteman, Marc

doi:10.1016/j.clml.2022.04.023

Cited by 6 publications

(17 citation statements)

References 50 publications

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“…Finally, while the study aimed to capture patient preferences using explorative qualitative methods, to better estimate and quantify patient preferences, a stated preference methodology, that is suitable to generate preference weights would need to be used, such as a Discrete Choice Experiment (DCE) ( 50 ). While the current sample size, designed for a qualitative interview study, is not suitable to conduct a quantitative preference research ( 51 ), the current findings could potentially contribute to developing attributes for a future DCE ( 50 , 52 ). However, given the difficulties with recruiting the patients of interest, it might be challenging to reach a suitable sample size for a DCE study.…”

Section: Discussionmentioning

confidence: 96%

Exploring preferences of different modes of administration of hypomethylating agent treatments among patients with acute myeloid leukemia

Delmas,

Batchelder,

Arora

et al. 2023

Front. Oncol.

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IntroductionAbout half of patients with Acute Myeloid Leukemia (AML) are not eligible for Standard Induction Chemotherapy (SIC). Hypomethylating Agents (HMAs) intravenously (IV) or subcutaneously (SC) in a clinical setting are typically offered as an alternative. However, injectable HMAs may be burdensome for patients given the frequent hospital visits and side effects. This study explored patient treatment preferences for different modes of administration (MOA) and the relative importance of treatment-related characteristics that influence treatment decisions.MethodsSemi-structured 1:1 interviews were conducted with 21 adult patients with AML in Germany, the United Kingdom, and Spain, who are not eligible for SIC, had experience with HMAs or were scheduled to be treated with HMAs. After discussing their experience of living with AML and its treatments, patients were presented with hypothetical treatment scenarios to explore their preferences, and a ranking exercise to assess the relative importance of treatment characteristics that influence their treatment-decisions for AML.ResultsMost patients reported an overall preference for oral administration over parenteral routes (71%), mostly due to convenience. Those preferring IV or SC routes (24%) reasoned with faster speed of action and onsite monitoring. When presented with a hypothetical situation of a patient having to choose between two AML treatments that were identical except for their MOA, the majority preferred the oral route (76%). Regarding treatment characteristics that influence treatment decisions, patients most frequently reported efficacy (86%) and side effects (62%) as important, followed by mode of administration (29%), daily life impacts (24%) and location of treatment (hospital versus home) (14%). However, only efficacy and side effects were rated as number one deciding factors (67% and 19%, respectively). Patients most frequently rated dosing regimen (33%) as least important.ConclusionThe insights gained from this study may help support patients with AML who are receiving HMA treatment instead of SIC. A potential oral HMA with similar efficacy and tolerability profiles to injectable HMAs could influence treatment decisions. Furthermore, an oral HMA treatment might decrease the burden of parenteral therapies and improve patients’ overall quality of life. However, the extent of influence MOA has on treatment decisions requires further investigation.

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Section: Discussionmentioning

confidence: 96%

Exploring preferences of different modes of administration of hypomethylating agent treatments among patients with acute myeloid leukemia

Delmas,

Batchelder,

Arora

et al. 2023

Front. Oncol.

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“…Interest and preference toward oral formulations over IV/SC chemotherapy is well documented in the literature. Indeed, a recent 2022 study analyzing the online survey data from MDS patients revealed both a preference and perceived personal benefit from improved quality of life from receiving oral DEC-C in comparison to IV/SC treatment [ 21 ]. The distribution of IPSS risk subgroups within patients with MDS in our cohort was similar to that of representative patient samples in the existing literature, where the greatest proportion of patients was INT-1 followed by INT-2 and then high risk [ 14 , 26 ].…”

Section: Discussionmentioning

confidence: 99%

“…These single-agent therapies were approved by Health Canada for the treatment of patients with HR-MDS (and CMML for decitabine) who are not candidates for HSCT [ 17 , 18 , 19 , 20 ]. Although these drugs have been shown to induce hematologic improvement in approximately one-third of patients, their demanding subcutaneous (SC)/intravenous (IV) infusion schedules prove to be a barrier for treatment continuation [ 21 ]. While a Canadian national guideline for the management of MDS remains unavailable, Cancer Care Ontario guidelines acknowledge intravenous HMA’s potential role in transfusion dependence reversal and its use in compassionate palliative settings [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Decitabine/Cedazuridine in the Management of Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia in Canada

Yun,

Ding,

Dolley

et al. 2023

Current Oncology

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The management of myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) is limited and remains an unmet need. Decitabine/cedazuridine (DEC-C, ASTX727) is Canada’s first and only approved oral hypomethylating agent for MDS and CMML. We characterized the real-world use of DEC-C through a Canadian compassionate use program. Demographic and clinical data from 769 patients enrolled in Taiho Pharma Canada’s Patient Support Program were collected and analyzed. These patients represent a collection period from 10 November 2020 to 31 August 2022 with a median age of 76 years. Among 651 patients who started DEC-C, the median treatment duration was 4.2 cycles. The median overall and progression-free survival were 21.6 and 10.7 months, respectively. Among 427 patients who discontinued treatment, the majority (69.5%) stopped due to death (n = 164) or disease progression (n = 133). Multivariable cox regression showed that age, province of residence, blast counts, antibiotic prophylaxis, and number of dose reductions and delays were not significantly associated with overall and progression-free survival. DEC-C is a promising alternative to parenteral hypomethylating agent therapy, and it likely addresses an important unmet need for effective and convenient therapies in this setting.

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“…Survey data from patients receiving oral DEC-C suggest it has the potential to reduce treatment burden relative to IV or SC HMAs. 38,65 Trends from real-world data among patients receiving oral DEC-C suggest comparable or improved compliance compared with IV or SC HMAs. An analysis of HMA claims between patients receiving oral DEC-C at home versus IV or SC treatment in the clinical setting suggested comparable or improved compliance with oral DEC-C and a possible advantage in reducing treatment burden.…”

Section: Multidisciplinary Perspective: Considerations For Treatment ...mentioning

confidence: 99%

“…10,13 These agents have shown efficacy in their respective indications and may improve persistence compared with parenteral HMAs by causing less disruption to daily life, reducing the stress and discomfort associated with SC and IV formulations, and presenting an alternative, oral option for patients who are unable to receive IV or SC infusions. 38 Thus, oral HMAs have the potential to reduce the treatment burden and decrease rates of early discontinuation, resulting in improved QoL, efficacy, and survival for patients with MDS and AML. 39 Differences in the pharmacokinetics (PK) and pharmacodynamics (PD) of oral versus parenteral HMA formulations (Table 1) have implications for their potential toxicities, mechanisms of action, and planned use.…”

Section: Introductionmentioning

confidence: 99%

Clinical activity, pharmacokinetics, and pharmacodynamics of oral hypomethylating agents for myelodysplastic syndromes/neoplasms and acute myeloid leukemia: A multidisciplinary review

Haumschild,

Kennerly-Shah,

Barbarotta

et al. 2024

J Oncol Pharm Pract

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Objective To review the pharmacokinetic (PK)–pharmacodynamic (PD) profiles, disease setting, dosing, and safety of oral and parenteral hypomethylating agents (HMAs) for the treatment of myelodysplastic syndromes/neoplasms (MDS) and acute myeloid leukemia (AML), and to provide a multidisciplinary perspective on treatment selection and educational needs relating to HMA use. Data Sources Clinical and real-world data for parenteral decitabine and azacitidine and two oral HMAs: decitabine–cedazuridine (DEC-C) for MDS and azacitidine (CC-486) for AML maintenance therapy. Data Summary Differences in the PK–PD profiles of oral and parenteral HMA formulations have implications for their potential toxicities and planned use. Oral DEC-C (decitabine 35 mg and cedazuridine 100 mg) has demonstrated equivalent systemic area under the concentration-time curve (AUC) exposure to a 5-day regimen of intravenous (IV) decitabine 20 mg/m2 and showed no significant difference in PD. The AUC equivalence of oral DEC-C and IV decitabine means that these regimens can be treated interchangeably (but must not be substituted within a cycle). Oral azacitidine has a distinct PK–PD profile versus IV or subcutaneous azacitidine, and the formulations are not bioequivalent or interchangeable owing to differences in plasma time-course kinetics and exposures. Clinical trials are ongoing to evaluate oral HMA combinations and novel oral HMAs, such as NTX-301 and ASTX030. Conclusions Treatment with oral HMAs has the potential to improve quality of life, treatment adherence, and disease outcomes versus parenteral HMAs. Better education of multidisciplinary teams on the factors affecting HMA treatment selection may help to improve treatment outcomes in patients with MDS or AML.

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Patient Preferences for Benefits, Risks, and Administration Route of Hypomethylating Agents in Myelodysplastic Syndromes

Cited by 6 publications

References 50 publications

Exploring preferences of different modes of administration of hypomethylating agent treatments among patients with acute myeloid leukemia

Exploring preferences of different modes of administration of hypomethylating agent treatments among patients with acute myeloid leukemia

Decitabine/Cedazuridine in the Management of Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia in Canada

Clinical activity, pharmacokinetics, and pharmacodynamics of oral hypomethylating agents for myelodysplastic syndromes/neoplasms and acute myeloid leukemia: A multidisciplinary review

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