PROGNOSTIC IMPACT OF MINIMAL REDISUAL DISEASE ASSESSMENT IN ELDERLY PATIENTS WITH SECONDARY ACUTE MYELOID LEUKEMIA. A COMPARISON BETWEEN CPX-351 AND INTENSIFIED FLUDARABINE-BASED REGIMENS
Author(s): ,
Fabio Guolo
Affiliations:
Clinic of Hematology, Department of Internal Medicine (DiMI), University of Genoa,IRCCS Ospedale Policlinico San Martino,GENOVA,Italy
,
Paola Minetto
Affiliations:
Clinic of Hematology, Department of Internal Medicine (DiMI), University of Genoa,IRCCS Ospedale Policlinico San Martino,GENOVA,Italy
,
Marino Clavio
Affiliations:
Clinic of Hematology, Department of Internal Medicine (DiMI), University of Genoa,IRCCS Ospedale Policlinico San Martino,GENOVA,Italy
,
Maurizio Miglino
Affiliations:
Clinic of Hematology, Department of Internal Medicine (DiMI), University of Genoa,IRCCS Ospedale Policlinico San Martino,GENOVA,Italy
,
Riccardo Marcolin
Affiliations:
Clinic of Hematology, Department of Internal Medicine (DiMI), University of Genoa,IRCCS Ospedale Policlinico San Martino,GENOVA,Italy
,
Monica Passannante
Affiliations:
Clinic of Hematology, Department of Internal Medicine (DiMI), University of Genoa,IRCCS Ospedale Policlinico San Martino,GENOVA,Italy
,
Michela Frello
Affiliations:
Clinic of Hematology, Department of Internal Medicine (DiMI), University of Genoa,IRCCS Ospedale Policlinico San Martino,GENOVA,Italy
,
Elisabetta Tedone
Affiliations:
Service of Flow Cytometry,IRCCS Ospedale Policlinico San Martino,GENOVA,Italy
,
Nicoletta Colombo
Affiliations:
Clinic of Hematology, Department of Internal Medicine (DiMI), University of Genoa,IRCCS Ospedale Policlinico San Martino,GENOVA,Italy
,
Enrico Carminati
Affiliations:
Clinic of Hematology, Department of Internal Medicine (DiMI), University of Genoa,IRCCS Ospedale Policlinico San Martino,GENOVA,Italy
,
Girolamo Pugliese
Affiliations:
Clinic of Hematology, Department of Internal Medicine (DiMI), University of Genoa,IRCCS Ospedale Policlinico San Martino,GENOVA,Italy
,
Clara Nurra
Affiliations:
Clinic of Hematology, Department of Internal Medicine (DiMI), University of Genoa,IRCCS Ospedale Policlinico San Martino,GENOVA,Italy
,
Antonia Cagnetta
Affiliations:
Clinic of Hematology, Department of Internal Medicine (DiMI), University of Genoa,IRCCS Ospedale Policlinico San Martino,GENOVA,Italy
,
MIchele Cea
Affiliations:
Clinic of Hematology, Department of Internal Medicine (DiMI), University of Genoa,IRCCS Ospedale Policlinico San Martino,GENOVA,Italy
Roberto Massimo Lemoli
Affiliations:
Clinic of Hematology, Department of Internal Medicine (DiMI), University of Genoa,IRCCS Ospedale Policlinico San Martino,GENOVA,Italy
EHA Library. Guolo F. 06/09/21; 325219; EP459
Dr. Fabio Guolo
Dr. Fabio Guolo
Contributions
Abstract
Presentation during EHA2021: All e-poster presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: EP459

Type: E-Poster Presentation

Session title: Acute myeloid leukemia - Clinical

Background
Minimal residual disease (MRD) assessment retains high prognostic value in Acute Myeloid Leukemia patients (AML) undergoing intensive induction therapy. Widely available MRD techniques include multicolour flow cytometry (MFC), RT-PCR for recurrent genetic lesion and, for patients lacking specific markers, RT-PCR for the pan-leukemic marker WT1. However, most of the data on the prognostic value of MRD come from trials including younger patients treated with conventional 3+7 regimen.  AML arising from a previous myelodisplastic syndrome (s-AML) and therapy-related AML (t-AML) are usually under-represented in trial involving younger patients and are unlikely to respond to conventional induction. Few data are therefore available on the kinetics and the prognostic value of MRD in elderly s-AML and t-AML patients, particularly in the context of alternative induction regimens.

Aims
We evaluated MRD in a cohort of elderly s-AML or t-AML patients receiving induction therapy either with a fludarabine-containing regimen or CPX-351, in order to compare the probability of achieving MRD negativity, to disclose the prognostic value of MRD in this setting and to define the best time-points for MRD assessments. 

Methods
A total of 136 elderly (>60 year, median age 67, range 60-75) patients were analyzed in this study. Patients were treated between January 2005 and January 2020 in our Center, either with CPX-351 (n=35) or fludarabine- high dose cytarabine-idarubicin (FLAI), with (n=72) or without (n =29) gemtuzumab-ozogamicin (GO). MRD was retrospectively analyzed in all patients achieving hematological complete remission (CR) with both MFC and WT1 expression levels.All patients  were affected by s-AML or t-AML,  defined according to the WHO 2016 criteria.

Results
After induction, CR was achieved in 83 patients (61%). CR rate was 28/35 in patients treated with CPX-351 (80%), significantly higher when compared to patients receiving FLAI (55/101, 54.5%, p<0.05). The addition of GO to FLAI did not increase CR rate. Among CR patients, a total of  41 (49.4%) and 44 patients (53%) achieved MRD negativity, with MFC or WT1-based methods, respectively. MFC MRD negativity probability was higher among patients receiving CPX-351 as induction therapy (MFC MRD negativity rate of 16/28, 57% and 25/55, 45% in CR patients who received CPX-351 or FLAI, respectively, p<0.05). Adding GO to FLAI did not improve MRD negativity probability. Moreover, MRD showed significant prognostic value in terms of Overall Survival in all treatment group (2-year OS of 74 and 36% in patients with or without residual MFC MRD after induction, respectively, p<0.05). WT1-based MRD lead to similar results.

Conclusion
In conclusion MRD assessment retains a strong prognostic value and may help to identify patients with suboptimal response to treatment. The higher rate of MRD negativity observed with CPX-351 may be related with a more efficient anti-leukemic activity of the drug in this particular setting. The evaluation of MRD with both MFC and WT1-based assessment lead to superimposable conclusions and allowed us to obtain MRD data from virtually all AML patients treated in the selected time period.

Keyword(s): AML, Elderly, Therapy-related AML

Presentation during EHA2021: All e-poster presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: EP459

Type: E-Poster Presentation

Session title: Acute myeloid leukemia - Clinical

Background
Minimal residual disease (MRD) assessment retains high prognostic value in Acute Myeloid Leukemia patients (AML) undergoing intensive induction therapy. Widely available MRD techniques include multicolour flow cytometry (MFC), RT-PCR for recurrent genetic lesion and, for patients lacking specific markers, RT-PCR for the pan-leukemic marker WT1. However, most of the data on the prognostic value of MRD come from trials including younger patients treated with conventional 3+7 regimen.  AML arising from a previous myelodisplastic syndrome (s-AML) and therapy-related AML (t-AML) are usually under-represented in trial involving younger patients and are unlikely to respond to conventional induction. Few data are therefore available on the kinetics and the prognostic value of MRD in elderly s-AML and t-AML patients, particularly in the context of alternative induction regimens.

Aims
We evaluated MRD in a cohort of elderly s-AML or t-AML patients receiving induction therapy either with a fludarabine-containing regimen or CPX-351, in order to compare the probability of achieving MRD negativity, to disclose the prognostic value of MRD in this setting and to define the best time-points for MRD assessments. 

Methods
A total of 136 elderly (>60 year, median age 67, range 60-75) patients were analyzed in this study. Patients were treated between January 2005 and January 2020 in our Center, either with CPX-351 (n=35) or fludarabine- high dose cytarabine-idarubicin (FLAI), with (n=72) or without (n =29) gemtuzumab-ozogamicin (GO). MRD was retrospectively analyzed in all patients achieving hematological complete remission (CR) with both MFC and WT1 expression levels.All patients  were affected by s-AML or t-AML,  defined according to the WHO 2016 criteria.

Results
After induction, CR was achieved in 83 patients (61%). CR rate was 28/35 in patients treated with CPX-351 (80%), significantly higher when compared to patients receiving FLAI (55/101, 54.5%, p<0.05). The addition of GO to FLAI did not increase CR rate. Among CR patients, a total of  41 (49.4%) and 44 patients (53%) achieved MRD negativity, with MFC or WT1-based methods, respectively. MFC MRD negativity probability was higher among patients receiving CPX-351 as induction therapy (MFC MRD negativity rate of 16/28, 57% and 25/55, 45% in CR patients who received CPX-351 or FLAI, respectively, p<0.05). Adding GO to FLAI did not improve MRD negativity probability. Moreover, MRD showed significant prognostic value in terms of Overall Survival in all treatment group (2-year OS of 74 and 36% in patients with or without residual MFC MRD after induction, respectively, p<0.05). WT1-based MRD lead to similar results.

Conclusion
In conclusion MRD assessment retains a strong prognostic value and may help to identify patients with suboptimal response to treatment. The higher rate of MRD negativity observed with CPX-351 may be related with a more efficient anti-leukemic activity of the drug in this particular setting. The evaluation of MRD with both MFC and WT1-based assessment lead to superimposable conclusions and allowed us to obtain MRD data from virtually all AML patients treated in the selected time period.

Keyword(s): AML, Elderly, Therapy-related AML

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