Clinical Outcomes of 217 Patients with Acute Erythroleukemia According to Treatment Type and Line: A Retrospective Multinational Study

Antonio M Almeida, Thomas Prebet, Raphael Itzykson, Fernando Ramos, Haifa Al-Ali, Jamile Shammo, Ricardo Pinto, Luca Maurillo, Jaime Wetzel, Pellegrino Musto, Arjan A Van De Loosdrecht, Maria Joao Costa, Susana Esteves, Sonja Burgstaller, Reinhard Stauder, Eva M Autzinger, Alois Lang, Peter Krippl, Dietmar Geissler, Jose Francisco Falantes, Carmen Pedro, Joan Bargay, Guillermo Deben, Ana Garrido, Santiago Bonanad, Maria Diez-Campelo, Sylvain Thepot, Lionel Ades, Wolfgang R Sperr, Peter Valent, Pierre Fenaux, Mikkael A Sekeres, Richard Greil, Lisa Pleyer, Antonio M Almeida, Thomas Prebet, Raphael Itzykson, Fernando Ramos, Haifa Al-Ali, Jamile Shammo, Ricardo Pinto, Luca Maurillo, Jaime Wetzel, Pellegrino Musto, Arjan A Van De Loosdrecht, Maria Joao Costa, Susana Esteves, Sonja Burgstaller, Reinhard Stauder, Eva M Autzinger, Alois Lang, Peter Krippl, Dietmar Geissler, Jose Francisco Falantes, Carmen Pedro, Joan Bargay, Guillermo Deben, Ana Garrido, Santiago Bonanad, Maria Diez-Campelo, Sylvain Thepot, Lionel Ades, Wolfgang R Sperr, Peter Valent, Pierre Fenaux, Mikkael A Sekeres, Richard Greil, Lisa Pleyer

Abstract

Acute erythroleukemia (AEL) is a rare disease typically associated with a poor prognosis. The median survival ranges between 3-9 months from initial diagnosis. Hypomethylating agents (HMAs) have been shown to prolong survival in patients with myelodysplastic syndromes (MDS) and AML, but there is limited data of their efficacy in AEL. We collected data from 210 AEL patients treated at 28 international sites. Overall survival (OS) and PFS were estimated using the Kaplan-Meier method and the log-rank test was used for subgroup comparisons. Survival between treatment groups was compared using the Cox proportional hazards regression model. Eighty-eight patients were treated with HMAs, 44 front line, and 122 with intensive chemotherapy (ICT). ICT led to a higher overall response rate (complete or partial) compared to first-line HMA (72% vs. 46.2%, respectively; p ≤ 0.001), but similar progression-free survival (8.0 vs. 9.4 months; p = 0.342). Overall survival was similar for ICT vs. HMAs (10.5 vs. 13.7 months; p = 0.564), but patients with high-risk cytogenetics treated with HMA first-line lived longer (7.5 for ICT vs. 13.3 months; p = 0.039). Our results support the therapeutic value of HMA in AEL.

Keywords: acute erythroleukemia; azacitidine; decitabine.

Conflict of interest statement

Antonio M. Almeida: speaker and advisory board for Celgene; Arjan A. Van De Loosdrecht: speaker and advisory board Celgene, advisory board Novartis; Jamile Shammo: Received research funding and honoraria for speaking engagements and consultancy from Celgene; Peter Valent received a research grant and speaker´s honoraria from Celgene and served as an advisory board member for Celgene. Fernando Ramos: Honoraria/Consultation fees for Celgene, Janssen, Amgen, Novatis, Pfizer, Glaxo-Smith-Kline, Merck-Sharp & Dohme. Maria Diez Campelo: speaker, research founding and advisory boards for Celgene.

Figures

Figure 1
Figure 1
(A) Overall survival of HMA-treated patients stratified by cytogenetic risk group (total HMA cohort): the median OS for patients treated with HMA was superior for patients with intermediate-compared to high-risk cytogenetics (13.5 months vs. 12.3 months; p = 0.0376); and (B) the overall survival by response to HMA: the median survival in patients with CR was 18.2 months, 12.7 months in patients with PR or HI, and 4.5 months in patients with no response (SD or primary PD; p < 0.001).
Figure 1
Figure 1
(A) Overall survival of HMA-treated patients stratified by cytogenetic risk group (total HMA cohort): the median OS for patients treated with HMA was superior for patients with intermediate-compared to high-risk cytogenetics (13.5 months vs. 12.3 months; p = 0.0376); and (B) the overall survival by response to HMA: the median survival in patients with CR was 18.2 months, 12.7 months in patients with PR or HI, and 4.5 months in patients with no response (SD or primary PD; p < 0.001).
Figure 2
Figure 2
Overall survival of AEL patients stratified by type of first line treatment. (A) Total cohorts: median OS for patients treated with first-line HMA was similar to that of those treated with first-line ICT (13.7 months vs. 10.5 months; p = 0.564); (B) stratified by MRC intermediate cytogenetic risk: AEL-patients with intermediate-risk cytogenetics treated with first-line HMA did not have a significantly different median survival as compared to AEL-patients treated with first-line ICT (16.9 months vs. 29.3 months; p = 0.277); and (C) stratified by MRC high cytogenetic risk: AEL-patients with high-risk cytogenetics treated with first-line HMA had a significantly longer median survival as compared to AEL-patients treated with first-line ICT (13.3 months vs. 7.5 months; p = 0.0391).
Figure 2
Figure 2
Overall survival of AEL patients stratified by type of first line treatment. (A) Total cohorts: median OS for patients treated with first-line HMA was similar to that of those treated with first-line ICT (13.7 months vs. 10.5 months; p = 0.564); (B) stratified by MRC intermediate cytogenetic risk: AEL-patients with intermediate-risk cytogenetics treated with first-line HMA did not have a significantly different median survival as compared to AEL-patients treated with first-line ICT (16.9 months vs. 29.3 months; p = 0.277); and (C) stratified by MRC high cytogenetic risk: AEL-patients with high-risk cytogenetics treated with first-line HMA had a significantly longer median survival as compared to AEL-patients treated with first-line ICT (13.3 months vs. 7.5 months; p = 0.0391).

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