Representation of therapy-related myelodysplastic syndrome in clinical trials over the past 20 years

Borate, Uma; Norris, Brianna; Statler, Abby; Fu, Rongwei; Bucy, Taylor; Sekeres, Mikkael A.

doi:10.1182/bloodadvances.2019000293

Cited by 10 publications

(14 citation statements)

References 52 publications

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“…These are likely highly enriched for therapy‐related disease or may have had a very acute disease course that precluded trial participation; this is corroborated by the fact that the time to treatment was significantly longer for trial participants than nonparticipants. Only 10% of trial participants (in contrast to 24% of nonparticipants) had a diagnosis of therapy‐related MDS in our cohort, and this underscores the lack of trial provision for therapy‐related MDS 13 . Many clinical trials expressly exclude patients with a history of neoplasia, and this reflects how narrow trial eligibility criteria are a major issue in catering to this cohort of patients, who in fact have the greatest need for novel therapies 21 .…”

Section: Discussionmentioning

confidence: 84%

“…Only 10% of trial participants (in contrast to 24% of nonparticipants) had a diagnosis of therapy-related MDS in our cohort, and this underscores the lack of trial provision for therapy-related MDS. 13 Many clinical trials expressly exclude patients with a history of neoplasia, and this reflects how narrow trial eligibility criteria are a major issue in catering to this cohort of patients, who in fact have the greatest need for novel therapies. 21 This unmet need and the resultant required recruitment of patients with high-risk MDS into clinical trials upfront are exemplified by the fact that the survival benefit observed in the hallmark AZA-001 HMA trial has not been replicated in subsequent real-world studies.…”

Section: Discussionmentioning

confidence: 99%

“…12 Approximately 20% of MDS cases are related to therapy and occur secondary to treatment for a prior malignancy; clinical trials frequently exclude patients in this cohort. 13 This subgroup has a high prevalence of TP53 mutation and complex karyotype, which confer chemoresistance and a dire prognosis, so trials are particularly important for this subgroup. 14 Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only option for long-term survival for patients with MDS, but its use is limited by age and comorbidity.…”

Section: Introductionmentioning

confidence: 99%

“…Real‐world data for patients have failed to replicate this efficacy and demonstrated a median OS of 14 months for patients with high‐risk MDS receiving HMA therapy 12 . Approximately 20% of MDS cases are related to therapy and occur secondary to treatment for a prior malignancy; clinical trials frequently exclude patients in this cohort 13 . This subgroup has a high prevalence of TP53 mutation and complex karyotype, which confer chemoresistance and a dire prognosis, so trials are particularly important for this subgroup 14 .…”

Section: Introductionmentioning

confidence: 99%

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Low participation rates and disparities in participation in interventional clinical trials for myelodysplastic syndromes

Brierley

Zabor

Komrokji

et al. 2020

Cancer

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BACKGROUND: The development of novel therapies for the myelodysplastic syndromes (MDS) is hampered by inadequate trial recruitment. Factors contributing to low trial accrual are incompletely understood. METHODS: This study analyzed a pooled patient database from institutions of the US MDS Clinical Research Consortium to compare the characteristics of participants in interventional trials with those of patients who did not enroll in a trial. RESULTS: Data were identified for 1919 patients with MDS, and 449 of these patients (23%) participated in an interventional clinical trial. The median age of all patients was 68 years, and 64% were male. Patients who participated in trials were significantly younger than nonparticipants (P = .014), and men were more likely to participate in a trial (71% of trial participants were male, whereas 61% of nonparticipants were; P < .001). Race and ethnicity were not associated with trial enrollment. Patients in more affluent ZIP codes had a higher participation rate (P < .001). Patients with intermediate-and high-risk disease according to the revised International Prognostic Scoring System were overrepresented (P = .004), and trial participants less frequently had treatment-related disease (P < .001). In multivariable analyses, participation in a clinical trial was associated with a reduced hazard of death (P = .004). Even at large referral centers, only a minority of patients with MDS enrolled in interventional trials. CONCLUSIONS: Restrictive trial eligibility criteria that exclude patients with MDS on account of age, comorbidities, or a history of another cancer are limit enrollment of MDS patients to clinical trials. Gaining insight into the barriers to trial accrual may help investigators and study sponsors to design trials that will accrue more rapidly and augment treatment options for patients with MDS.

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Low participation rates and disparities in participation in interventional clinical trials for myelodysplastic syndromes

Brierley

Zabor

Komrokji

et al. 2020

Cancer

Self Cite

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“…In contrast, publications on t-MDS only are rare [21][22][23]. Not categorizing t-MDS as a subgroup of MDS limits proper clinical decision-making, interferes with epidemiological/ biological research, and supports the established practice of excluding t-MDS from clinical studies [24], thereby potentially preventing therapeutic improvements.…”

Section: Introductionmentioning

confidence: 99%

Therapy-related myelodysplastic syndromes deserve specific diagnostic sub-classification and risk-stratification—an approach to classification of patients with t-MDS

et al. 2020

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In the current World Health Organization (WHO)-classification, therapy-related myelodysplastic syndromes (t-MDS) are categorized together with therapy-related acute myeloid leukemia (AML) and t-myelodysplastic/myeloproliferative neoplasms into one subgroup independent of morphologic or prognostic features. Analyzing data of 2087 t-MDS patients from different international MDS groups to evaluate classification and prognostication tools we found that applying the WHO classification for p-MDS successfully predicts time to transformation and survival (both p < 0.001). The results regarding carefully reviewed cytogenetic data, classifications, and prognostic scores confirmed that t-MDS are similarly heterogeneous as p-MDS and therefore deserve the same careful differentiation regarding risk. As reference, these results were compared with 4593 primary MDS (p-MDS) patients represented in the International Working Group for Prognosis in MDS database (IWG-PM). Although a less favorable clinical outcome occurred in each t-MDS subset compared with p-MDS subgroups, FAB and WHO-classification, IPSS-R, and WPSS-R separated t-MDS patients into differing risk groups effectively, indicating that all established risk factors for p-MDS maintained relevance in t-MDS, with cytogenetic features having enhanced predictive power. These data strongly argue to classify t-MDS as a separate entity distinct from other WHO-classified t-myeloid neoplasms, which would enhance treatment decisions and facilitate the inclusion of t-MDS patients into clinical studies.

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Secondary AML Emerging After Therapy with Hypomethylating Agents: Outcomes, Prognostic Factors, and Treatment Options

Richardson

Green

Foster

et al. 2021

Curr Hematol Malig Rep

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Representation of therapy-related myelodysplastic syndrome in clinical trials over the past 20 years

Abstract: Key PointsPatients with t-MDS are underrepresented in clinical trials when taking into account the prevalence of such patients. Eligibility criteria and sponsorship type may contribute to t-MDS patient exclusion.

Cited by 10 publications

References 52 publications

Low participation rates and disparities in participation in interventional clinical trials for myelodysplastic syndromes

Low participation rates and disparities in participation in interventional clinical trials for myelodysplastic syndromes

Therapy-related myelodysplastic syndromes deserve specific diagnostic sub-classification and risk-stratification—an approach to classification of patients with t-MDS

Secondary AML Emerging After Therapy with Hypomethylating Agents: Outcomes, Prognostic Factors, and Treatment Options

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