Abstract
We evaluated the predictive value of the ex-vivo PharmaFlow PM platform in measuring the pharmacological activity of drug combinations consisting of 20 different chemotherapy regimens (20 Tx) administered in 104 acute myeloid leukemia (AML) patients. The predicted sensitivities of alternative treatments for each patient were ranked in five 20% categories, from resistant to sensitive (Groups 1–5). The complete remission (CR) rates of the five groups were 0%, 12.5%, 38.5%, 50.0%, and 81.3%, respectively. The heat map showed a good relationship between drug sensitivity with CR (Group 4 + 5 vs. Group 1 + 2+3: 77.5% vs. 27.3%, p = 0.002) and the European Leukemia Net risk group (22.6% vs. 63.6%, p = 0.015). The predicted coincidence rate was 90.9% in Group 1 + 2 and 81.3% in Group 5. According to the recommendations of the PharmaFlow PM platform, the CR rate would have increased by about 16.3% in one cycle. The overall survival (OS) was shorter in patients predicted to be resistant (Group 1 + 2 vs. Group 3 + 4+5, p = 0.086). In multivariable analysis, CR after one cycle was an independent prognostic factor for OS [p = 0.001; 95% CI 0.202 (0.080–0.511)], and ex-vivo chemosensitivity was a potential predictive factor for OS [p = 0.078; 95% CI 0.696 (0.465–1.041)]. To conclude, the PharmaFlow PM platform is a rapid and valuable tool for predicting clinical response and outcomes in AML patients.
Highlights
Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy and is the most common type of adult leukemia
The diagnostic and classification criteria were based on the 2016 World Health Organization (WHO) [19] and 2017 European Leukemia Net (ELN) criteria [20]
The ELN 2017 results were obtained in all patients; favorable and adverse karyotypes were found in 33.6% (35/104) and 26.9% (28/104) patients, respectively
Summary
Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy and is the most common type of adult leukemia. About 60% of newly diagnosed AML patients receiving frontline therapy attain a complete remission (CR), yet 30%–40% of patients experience relapse [1, 2]. Treatment for relapsed patients is difficult and limited [3]. Refractoriness to induction therapy and relapse after CR are still the most challenging aspects in AML. The 5-year overall survival (OS) of AML patients aged younger than and older than 60 years is about 30%–40% and less than 15%, respectively [4, 5]. The diagnosis of AML is based on the morphology, immunology, cytogenetics, and molecular biology (MICM) characteristics, treatment regimens often made based on the doctors’ experience. How to formulate individualized treatment plans for patients based on multiple drug combinations is the unmet need of AML treatment
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