Autore F, et al. APL 2017:PO050

Long-term follow-up of first-line ATO in combination with ATRA compared to chemotherapy in combination with ATRA in patients with APL: Monocentric experience

Background

At the 7th International Symposium on APL, Autore and colleagues presented their experience of patients with acute promyelocytic leukemia (APL) treated with arsenic trioxide (ATO) plus all-trans retinoic acid (ATRA) compared to those treated with chemotherapy plus ATRA in the long term.1

Study design

  • From January 2009, patients with APL were treated with ATO plus ATRA according to the GIMEMA protocol in the APL0406 trial (first arm),2 or with chemotherapy plus ATRA according to the AIDA-2000 study (second/control arm).3

Key findings

  • There were 12 patients in the first arm and 12 patients in the control arm.
  • Patients’ characteristics were as follows:
    • The median age in the first and control arms was 45.5 and 42 years, respectively.
    • The white blood cell count was 1,070 mm3 (range: 650–9,770) in the first arm and 3,350 mm3 (range: 800–117,000) in the control arm.
    • There were four patients in the control arm with high-risk APL, compared to no patients in the first arm.
  • During treatment, brief interruptions of ATO were registered in seven patients, and ATRA syndrome was described in five patients in the first arm; ATRA syndrome was also reported in six patients in the control arm.
  • Adverse events (AEs) in the induction phase were reported as follows:
    • In the first arm, two thrombotic events, two herpes simplex virus (HSV) infections, and one ATRA myopathy were reported.
    • In the control arm, eight fever cases requiring antibiotics, five hemorrhagic complications, one thrombophlebitis, and one benign endocranial hypertension were reported.
  • Molecular remission was achieved in all patients after a median time of 3 months in both groups.
  • AEs in the consolidation phase were reported as follows:
    • In the first arm, two patients required dose reduction of ATO due to corrected QT prolongation; one patient experienced benign endocranial hypertension; one patient experienced mild hepatotoxicity; and one patient had HSV infection.
    • In the control arm, nine patients showed neutropenic fever; two patients had a thrombotic event; and one patient experienced mild hepatotoxicity.
  • During the maintenance phase, hepatotoxicity of different grades and neutropenia were common in both arms.
  • All patients in the first arm remained in molecular response at a median time of 16 months (range: 2–91), with the exception of one patient, who showed the reappearance of promyelocytic leukemia-retinoic acid receptor alpha in the bone marrow after 11 months.
    • This patient restarted ATO plus ATRA, and achieved molecular complete remission at the three-month control.
  • All patients in the control arm were in molecular response for a median time of 43.5 months (range: 30–97), but two patients developed myelodysplastic syndrome (MDS) after a few months and three years after the maintenance phase, respectively.
  • All patients in the first arm remain alive and in response at a median follow-up of 19 months (range: 4–94), with no late effects registered.
  • In the control arm, all patients remain alive after a median time of 47 months (range: 35–100), except for two patients who developed MDS and died.
  • Only nine patients in the first arm required platelet or red blood cell transfusion, whereas all patients in the control arm required transfusion support and fresh frozen plasma.
    • During the consolidation phase, no patients in the first arm versus nine patients in the control arm required transfusion support.

Key conclusions

  • The treatment of ATO plus ATRA was well tolerated, and showed advantages in comparison to chemotherapy plus ATRA.
  • The ATO plus ATRA regimen reduced the need for transfusion support during treatment.
  • ATO plus ATRA also reduced the risk of MDS.

References: 1. Autore F, Chiusolo P, Sorà F, et al. Long-term follow-up of 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:PO050. 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.