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

Abstract

Few patients with cancer, including those with acute myeloid leukemia and high-grade myeloid neoplasms, participate in clinical trials. Broadening standard eligibility criteria may increase clinical trial participation. In this retrospective single-center analysis, we identified 442 consecutive newly diagnosed patients from 2014 to 2016. Patients were considered “eligible” if they had a performance status 0-2, normal renal and hepatic function, no recent solid tumor, left ventricular ejection fraction (EF) ≥50%, and no history of congestive heart failure (CHF) or myocardial infarction (MI); “ineligible” patients failed to meet one or more of these criteria. We included 372 patients who received chemotherapy. Ineligible patients represented 40% of the population and had a 1.79-fold greater risk of death (95% Confidence Interval [CI]: 1.37-2.33) than eligible patients. Very few patients had cardiac comorbidities, including 2% with low EF, 4% with prior CHF, and 5% with prior MI. In multivariable analysis, ineligibility was associated with decreased survival (Hazard ratio [HR] 1.44; 95% CI: 1.07-1.93). Allogeneic transplantation, performed in 150 patients (40%), was associated with improved survival (HR 0.66, 95% CI: 0.48-0.91). Therefore, standard eligibility characteristics identify a patient population with improved survival. Further treatment options are needed for patients considered ineligible for clinical trials.

Acute myeloid leukemia: 2021 update on risk‐stratification and management

“…Several validated multivariate models are available to quantify this risk, 42,50,52,53 which should not be based on age alone 30 and should be made while cognizant of the primary cause of treatment failure even in most older patients, at least those referred to academic centers, has been resistance to therapy rather than TRM 48,49 . A problem of course is many patients at high risk of TRM are often excluded from trials (even those said to be testing therapies for unfit patients), because of performance status or co‐morbidities, with excluded patients having demonstrably worse outcomes 74 . A trial whose eligibility criteria were essentially ineligibility for standard trials, has demonstrated the potentially favorable benefit/risk ratio of such more inclusive trials 75 …”

Practice patterns and outcomes for adults with acute myeloid leukemia receiving care in community vs academic settings

“…7 Whether better access to clinical trials at academic centers translates into better outcomes (trial effect) remains controversial 13,[15][16][17] ; restrictive eligibility criteria for trial participation may bias such analyses. 18 Perhaps unsurprisingly, the center effect in AML extends to survival outcomes with allogeneic stem cell transplantation (HCT), which are closely linked to overall AML outcomes. 19 Whether such benefits extend to other post-HCT composite endpoints such as graft-versus-host disease-free, relapse-free survival is, although plausible, currently unknown.…”

Acute myeloid leukaemia in patients we judge as being older and/or unfit

“…CPX‐351 appears to be well tolerated, with lower 30‐ and 60‐day mortality, more patients transitioning to allogeneic SCT and consequentially improved post‐transplant survival. Recently updated data with 5 years of follow‐up confirmed the improved OS of CPX‐351 compared with 3 + 7 in the target population (18 vs 8%) [37]. Results of the study led to the FDA and subsequently EMA approval of CPX‐ 351 as induction therapy in patients with t‐AML and AML with myelodysplasia‐related changes (MRC) [10].…”