Patterns of undertreatment among patients with acute myeloid leukemia (AML): considerations for patients eligible for non-intensive chemotherapy (NIC)

Abstract

Acute myeloid leukemia (AML) is a life-threatening malignancy that is more prevalent in the elderly. Because the patient population is heterogenous and advanced in age, choosing the optimal therapy can be challenging. There is strong evidence supporting antileukemic therapy, including standard intensive induction chemotherapy (IC) and non-intensive chemotherapy (NIC), for older patients with AML, and guidelines recommend treatment selection based on a patient’s individual and disease characteristics as opposed to age alone. Nonetheless, historic evidence indicates that a high proportion of patients who may be candidates for NIC receive no active antileukemic treatment (NAAT), instead receiving only best supportive care (BSC). We conducted a focused literature review to assess current real-world patterns of undertreatment in AML. From a total of 25 identified studies reporting the proportion of patients with AML receiving NAAT, the proportion of patients treated with NAAT varied widely, ranging from 10 to 61.4% in the US and 24.1 to 35% in Europe. Characteristics associated with receipt of NAAT included clinical factors such as age, poor performance status, comorbidities, and uncontrolled concomitant conditions, as well as sociodemographic factors such as female sex, unmarried status, and lower income. Survival was diminished among patients receiving NAAT, with reported median overall survival values ranging from 1.2 to 4.8 months compared to 5 to 14.4 months with NIC. These findings suggest a proportion of patients who are candidates for NIC receive NAAT, potentially forfeiting the survival benefit of active antileukemic treatment.

Acute myeloid leukemia: Incidence, transplantation and survival through Italian administrative healthcare data

“…This evidence should probably be seen in the light of additional factors other than age, such as comorbidity burden, performance status, disease-related variables, sex, income status, improvement in supportive care and peri-alloSCT strategies, increased use of alloSCT, and treatment settings. 1,8,27 In line with expectations and literature, our findings showed significant (p<0.0001) higher OS probabilities at both one and two years after the new AML diagnosis among patients treated with ICHT, who were diagnosed younger than subjects unfit for ICHT. Nevertheless, it is worth remembering that clinical recommendations are still mostly based on findings from CTs that are conducted on patients younger and fitter than the real-world community, making it difficult to contextualize them in real practice.…”

“…7,11,26 This choice was mostly based on evidence that age at diagnosis plays a significant role in the long-term survival of AML patients 1 (i.e., high mortality rates at three and five years and higher comorbidity frequencies leading to increased mortality) 27 ; while, very few CTs have been carried out in older patients, 27 in great contrast with the real-world epidemiology. 8,12 The use of the age as decisive determinant to guide therapy is still conflicting; indeed, recent studies have suggested a multidisciplinary assessment of functional age and variables not strictly AML-related. [6][7][8]12,13,27 A proportion of 32.0% of subjects treated with ICHT were not affected by any comorbidities, while 38.6% of those unfit for ICHT presented three or more concomitant diseases, as expected from their respective mean ages (±SD) 65±14 and 72±14.…”

“…8,12 The use of the age as decisive determinant to guide therapy is still conflicting; indeed, recent studies have suggested a multidisciplinary assessment of functional age and variables not strictly AML-related. [6][7][8]12,13,27 A proportion of 32.0% of subjects treated with ICHT were not affected by any comorbidities, while 38.6% of those unfit for ICHT presented three or more concomitant diseases, as expected from their respective mean ages (±SD) 65±14 and 72±14. As in literature, hypertension, diabetes and dyslipidaemia were prevalent in both cohorts, 23 but, interestingly, these comorbidities are not likely to be considered by clinicians as a limitation to the use of ICHT.…”

“…6,11 Meanwhile, recent studies have suggested a multidisciplinary assessment of functional age and variables not strictly AML-related. 7,8,12,13 This observational retrospective analysis of the Fondazione Ricerca e Salute's (ReS -Research and Health Foundation) database aimed at identifying AML incidence in 2017 and describing newly diagnosed patients treated with ICHT or unfit for ICHT, their probability of receiving the alloSCT and of two-year overall survival, from the perspective of the Italian National Health Service (INHS).…”

BCL2 Inhibition: A New Paradigm for the Treatment of AML and Beyond

“…Before introduction of VEN, for patients aged >65 years with AML, no active antileukemic therapy was offered to ~1 of 3 patients in the US and Europe, with the OS expectations ranging between 1.2 and 4.8 months. 95 Over the last 15 years, the genomic structure of AML by next-gen sequencing made the potential for parallel advances in AML therapy seem highly challenging, especially for the patient population considered unfit for intensive chemotherapy. 96,97 The elevation of VEN to its current role in AML has required a series of major barriers to be hurdled.…”