A comparison of patients with acute myeloid leukemia and high-risk myelodysplastic syndrome treated on versus off study

Abstract

Patients with newly diagnosed (ND) and relapsed/refractory (RR) acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS, ≥10% blasts) often receive intensive chemotherapy at diagnosis and relapse. We retrospectively identified 365 patients and categorized the reasons for receiving treatment off study (medical, logistical, or unclear). The pre-treatment characteristics of the on and off study groups were similar. Rates of complete remission (CR) without measurable residual disease were significantly higher for ND patients treated on vs. off study (61% vs. 35%), but CR rates and survival were low for all RR patients regardless of study assignment. The subset of ND patients treated off study for medical reasons had significantly decreased overall survival and relapse-free survival. Standard, stringent study eligibility criteria may delineate a population of ND, but not RR, patients with improved outcomes with intensive induction chemotherapy.

Survival of patients with newly diagnosed high-grade myeloid neoplasms who do not meet standard trial eligibility

“…Our finding that ineligibility is associated with decreased survival suggests that standard clinical trial criteria may identify a population of patients with better outcomes following treatment; improved responses and survival have also been demonstrated in an “on study” population when the same induction regimen was administered to patients both on and off clinical trial at our center and in a national population-based cohort study from Denmark. 17 , 18 These findings contrast some with the Statler analysis of AML patients, which did not identify significant differences in response or survival based on comorbidities other than liver disease and organ dysfunction. 6 In the future, evaluation of other factors including travel distance, social support, and frailty level could provide a more nuanced picture of eligibility.…”

Good but not good enough: Clinical trial participation of patients with myelodysplastic syndromes

“…Although the authors adjusted their multivariable analysis for known risk factors for an adverse outcome such as age and IPSS‐R risk group, other confounders such as comorbidities and the rate of therapy‐related MDS were not captured in the analysis, and this limits the interpretation of the finding 13,17 . Although it is also possible that outcomes for patients enrolled in clinical trials are superior because of potentially closer monitoring as part of the clinical trial as well as benefits of the trial regimens themselves, differences in baseline patient characteristics and trial enrollment have been shown in patients with acute myeloid leukemia treated on and off trial as well and are likely to explain the mortality benefit for patients treated on trial 18 . However, the fact that patients enrolled in clinical trials differ substantially in terms of social determinants of health is a worrisome finding that is also seen in other cancer trials, and efforts to improve outcomes for all patients are warranted 19 …”

“…13,17 Although it is also possible that outcomes for patients enrolled in clinical trials are superior because of potentially closer monitoring as part of the clinical trial as well as benefits of the trial regimens themselves, differences in baseline patient characteristics and trial enrollment have been shown in patients with acute myeloid leukemia treated on and off trial as well and are likely to explain the mortality benefit for patients treated on trial. 18 However, the fact that patients enrolled in clinical trials differ substantially in terms of social determinants of health is a worrisome finding that is also seen in other cancer trials, and efforts to improve outcomes for all patients are warranted. 19 With an annual age-adjusted incidence rate of 4 per 100,000 persons in the United States, MDS is a rare disease, and clinical trial recruitment requires concerted efforts.…”