Autore F, et al. APL 2017:PO029

Reduction of hospitalization and transfusion support with first-line ATO in combination with ATRA compared to chemotherapy in combination with ATRA in patients with APL: Monocentric experience

Background

All-trans retinoic acid (ATRA) in combination with anthracycline-based chemotherapy has obtained high response rates, but is associated with potential long-term sequelae in patients with acute promyelocytic leukemia (APL). The combination of arsenic trioxide (ATO) and ATRA was introduced in an attempt to obviate these complications. The aim of this study was to compare the number of hospitalization days and number of transfusions in patients with APL who received ATO plus ATRA to those who received ATRA plus chemotherapy. Results were presented at the International Symposium on APL 2017.1

Study design

  • Twelve patients with APL were treated with ATO plus ATRA according to the GIMEMA protocol APL0406.2
  • The control group consisted of 12 patients who were treated with chemotherapy plus ATRA according to AIDA-2000.3

Key findings

Baseline characteristics and disposition

  • Patient characteristics are summarized in Table 1.
  • In the ATO plus ATRA group, there were patients for whom chemotherapy was not applicable because of prior chemotherapy (secondary APL), intracerebral hemorrhage, or massive pulmonary embolism at the onset of disease.

Safety

  • All patients started ATRA immediately and were admitted to the hospital for the induction phase.
    • The median length of first hospitalization after ATRA plus ATO therapy was 34 days (range: 28–47) and was 31 days (range: 25–46) in the ATRA plus chemotherapy group.
    • In the ATRA plus ATO group, the mean number of units of red blood cells (RBCs), platelets, and fresh frozen plasma (FFP) transfused during induction was 4.5, 7, and 3, respectively; in the ATRA plus chemotherapy group it was 4, 6, and 10, respectively.
  • In the ATRA plus ATO arm, 11 patients received the consolidation phase as outpatients.
    • During consolidation, one patient was hospitalized for suspected benign endocranial hypertension.
    • No transfusions were given during consolidation.
  • In the ATRA plus chemotherapy arm, all patients were hospitalized during the first two consolidations.
    • The median time of first consolidation recovery was six days (range: 5–7).
      • Ten patients needed a second admission for neutropenia and other complications that lasted a median of nine days (range: 7–15).
      • During the second admission, three patients received RBC and platelet transfusions.
    • During the second consolidation, the median time of first recovery was seven days (range: 6–9).
      • This was followed by a second admission of 11 days (range: 8–18).
      • Eight patients received platelet transfusions and six patients received RBC transfusions during this phase.
    • Two patients were admitted to the hospital for the third consolidation.
      • Five patients required hospitalization for complications during this phase, and one patient received a platelet transfusion.

Table 1. Baseline characteristics

Key conclusions

  • The ATRA plus ATO regimen allowed for the treatment of patients in whom chemotherapy could not be used.
  • Analyses showed that the ATRA plus ATO regimen reduced hospitalization and transfusion support.
    • Patients treated with ATRA plus chemotherapy received more FFP transfusions during induction (p = 0.003), received more RBC and platelet transfusions during consolidation (p <0.001), and experienced a higher number of hospital readmissions (p <0.001) compared to those treated with ATRA plus ATO.
  • The association of ATO to ATRA is an efficacious chemotherapy-free regimen and seems to reduce costs in terms of hospitalization and transfusion support.

References: 1. Autore F, Chiusolo P, Sorà F, et al. Reduction of hospitalization and transfusion support with first line arsenic trioxide in combination with all-trans retinoic acid compared to chemotherapy in combination with all-trans retinoic acid in patients with acute promyelocytic leukemia: monocentric experience. Intl. Symposium on APL Abstracts 2017:PO029. 2. Platzbecker U, Avvisati G, Cicconi L, et al. Improved outcomes with retinoic acid and arsenic trioxide compared with retinoic acid and chemotherapy in non–high-risk acute promyelocytic leukemia: final results of the randomized Italian-German APL0406 trial. J Clin Oncol 2017;35(6):605–12. 3. Lo-Coco F, Avvisati G, Vignetti M, et al. Front-line treatment of acute promyelocytic leukemia with AIDA induction followed by risk-adapted consolidation for adults younger than 61 years: results of the AIDA-2000 trial of the GIMEMA Group. Blood 2010;116(17):3171–9.