Salvage Therapy with Chemotherapy- or Arsenic Trioxide-Based Regimens for Acute Promyelocytic Leukemia in First Relapse.
Authors: Montesinos Pau , Esteve Jordi , Vellenga Edo , Rivas Concha , Brunet Salut , Arnan Montserrat , Gonzalez Jose D. , Sanchez Pedro , Díaz-Mediavilla Joaquín , Verdeguer Amparo , Escoda Lourdes , Amutio Elena , Rubio Vicente , Perez Inmaculada , Guardia Ramon , Bueno Javier , Lowenberg Bob , Sanz Miguel A. 
Published: October 2019

Abstract
Abstract 1062
Poster Board I-84

Background:
Arsenic trioxide (ATO) is currently regarded as the best treatment option in relapsed acute promyelocytic leukemia (APL). The efficacy and safety of salvage therapy using an ATO-based approach compared with chemotherapy-based regimens is not well established. We analyze the clinical outcome of 110 APL patients relapsing after front-line therapy with ATRA and anthracycline, who received second-line therapy with chemotherapy- or ATO-based regimens.

Methods:
From June 1997 to May 2009, 110 patients (69 M/41 F; median age: 40 years, 2-81) relapsed after front-line therapy with PETHEMA trials (LPA96, n=30, LPA99, n=60; and LPA2005, n=20). Patients presented with either molecular relapse (n=37) or hematological relapse (n=73, 14 of them involving central nervous system). Sixty-seven patients (61%) followed salvage therapy with chemotherapy-based regimens. Therapy consisted of induction with mitoxantrone plus cytarabine plus ATRA (n=46), EMA (n=7), or other chemotherapy regimens (n=14). Thirty-four patients (51%) received one consolidation cycle followed by stem-cell transplantation (SCT) (autologous, 20; allogeneic, 14). Patients not eligible for SCT received consolidation therapy with or without maintenance therapy. From October 2003, 43 patients (49%) received salvage therapy with ATO-based regimens, comprising induction with ATO (0.15 mg/kg intravenously until CR) followed by one consolidation cycle with ATO plus ATRA. Twenty-three patients (53%) received intensification therapy with SCT (autologous, 19; allogeneic, 4). Patients not eligible for SCT received maintenance therapy with ATO plus ATRA with or without Mylotarg or other chemotherapy.

Results:
Baseline characteristics, including age at relapse, were similar in both cohorts of patients, but patients treated with ATO-based regimens were more frequently late relapses (>18 months after initial APL diagnosis) (67% vs. 40%, P=0.005). The median follow-up in the chemotherapy-based group was 62 months (range, 6-134), and 18 months (range, 2-53) in the ATO-based group. CR rates were 84% in the chemotherapy-based group (8 deaths and 3 resistances) and 88% in the ATO-based group (3 deaths and 2 resistances) (P=0.48). Molecular remission was achieved after consolidation in 79% and 91%, respectively (P=0.13). Twenty-two patients of the chemotherapy-based group that achieved CR were not transplanted because of ineligibility for SCT (n=4), early relapse before planned SCT (n=7), mobilization failure (n=4), clinical decision/toxicity (n=6), and short follow-up (n=1). Reasons for not SCT in the ATO-based group were ineligibility for SCT (n=6), early relapse before planned SCT (n=5), and short follow-up (n=4). The 2-year overall survival (OS), disease-free (DFS), and relapse-free survival (RFS) in the chemotherapy-based group and in the ATO-based group were 44% vs. 63% (P=0.05), 34% vs. 33% (P=0.51), and 37% vs. 34% (P=0.61), respectively. For patients not receiving SCT, the 2-year OS, DFS, and RFS in the chemotherapy-based group and in the ATO-based group were 38% vs. 26% (P=0.98), 34% vs. 23% (P=0.57), and 37% vs. 23% (P=0.46), respectively. For patients receiving autologous SCT, the 2-year OS, DFS, and RFS in the chemotherapy-based group and in the ATO-based group were 60% vs. 87% (P=0.03), 40% vs. 38% (P=0.38), and 42% vs. 41% (P=0.37), respectively. For patients receiving allogeneic SCT, the 2-year OS, DFS, and RFS in the chemotherapy-based group and in the ATO-based group were 56% vs. 100% (P=0.15), 26% vs. 37% (P=0.46), and 28% vs. 37% (P=0.53), respectively.

Conclusions:
this study performed in a large series of APL patients relapsing after upfront therapy with ATRA and anthracycline shows high rates of CR either with ATO (88%) or chemotherapy regimens (84%). The 2-year DFS and RFS were similar in patients who received second-line therapy with chemotherapy- or ATO-based regimens. However, an apparent benefit in terms of OS was observed in the ATO-based group (P=0.05), suggesting a potential role in minimizing toxicity after administering ATO as salvage therapy.

Disclosures:
No relevant conflicts of interest to declare.