Cicconi L, et al. APL 2017:CO032

Prolonged ATO and ATRA therapy for relapsed APL

Background

Arsenic trioxide (ATO) combined with all-trans retinoic acid (ATRA) is the standard salvage regimen for relapsed acute promyelocytic leukemia (APL); however, the optimal consolidation strategy remains undefined. The approach of giving prolonged ATO and ATRA with repeated cycles has not been investigated in relapsed APL. A retrospective analysis of patients with relapsed APL who were treated with prolonged ATO and ATRA at two Italian institutions was presented at the 7th International Symposium on APL.1

Study design

  • The objective of this retrospective study was to verify the efficacy of a prolonged ATO and ATRA therapy without subsequent stem cell transplant (SCT) in a cohort of patients with relapsed APL.
  • This study included 22 adult patients with relapsed APL who were treated at two Italian institutions between 2006 and 2017.
  • All patients received ATO and ATRA during both induction and consolidation, with or without subsequent SCT, as per dosing and scheduling in previous studies.2
  • Molecular analysis of the promyelocytic leukemia-retinoic acid receptor alpha translocation was performed by real-time quantitative polymerase chain reaction.

Key findings

  • The median age of patients was 43.5 years (range: 18–80) and the median duration of previous complete remission (CR) was 32.5 months (range: 5–120).
  • Of the 22 patients evaluated, 18 were being treated at first relapse and four were being treated at second or subsequent relapse.
  • The breakdown of relapse by type was as follows:
    • Hematological (n = 7);
    • Molecular (n = 14); and
    • Extramedullary (n = 3).
  • Front-line therapy included ATRA plus idarubicin (AIDA) in 20 patients and an amended AIDA regimen for two patients defined as elderly.
  • After two cycles of ATO and ATRA salvage therapy, molecular remission was achieved in 20 patients (90%).
    • Of these patients, one received subsequent autologous SCT and one received subsequent allogeneic SCT.
  • Of the 18 patients who did not receive an SCT, nine patients had a long previous molecular CR, five patients were unfit/elderly, two patients refused SCT, and two patients lacked a donor.
    • The median number of ATO and ATRA cycles was 5.
  • At a median follow-up of 58 months, 14 patients (68%) remained alive and in molecular remission, seven patients (32%) relapsed or were resistant to therapy, and one patient died while in molecular remission. (Table 1)
  • The Kaplan-Meier curve for disease-free survival is presented in Figure 1.

Key conclusions

  • Data from this analysis suggest that prolonged ATO and ATRA therapy without SCT intensification may be an option for relapsed APL.
  • A long first remission is associated with a higher probability of long-term molecular CR with prolonged ATO and ATRA.
  • Prospective studies investigating prolonged ATO and ATRA therapy in relapsed APL are warranted to confirm this preliminary data.

References: 1. Cicconi L, Brecchia M, Franceschini L, et al. Prolonged ATO and ATRA therapy for relapsed acute promyelocytic leukemia. Intl. Symposium on APL Abstracts 2017:CO032. 2. Lo-Coco F, Avvisati G, Vignetti M, et al. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med 2013;369(2):111–21.