Kayser S, et al. APL 2017:CO033

Characteristics and outcomes of therapy-related APL after different front-line therapies

Background

Information on the true incidence of therapy-related acute promyelocytic leukemia (t-APL) is scarce. However, the incidence appears to have increased in recent years, with some studies suggesting that the outcomes are similar to patients with de novo APL.1 The combined regimen of arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) is effective in de novo low- to intermediate-risk APL, but it has not been evaluated in a large cohort of patients with t-APL.2 At the 7th International Symposium on APL, Kayser and colleagues presented an analysis of outcomes in patients with t-APL according to different treatment strategies.3

Study design

  • A total of 103 patients with APL were retrospectively studied.
    • The patients had been treated between 1991 and 2015 across 11 study groups/institutions in the U.S. and Europe.
  • Patients had received one of the following four treatments:
    • Chemotherapy (CTX)/ATRA (n = 53);
    • ATO/ATRA (n = 24);
    • CTX/ATO/ATRA (n = 19); and
    • ATRA only (n = 7).

Key findings

Baseline characteristics

  • The median age of all patients was 59 years (range: 18–80).
  • There were no differences in baseline characteristics by gender, hemoglobin levels, lactate dehydrogenase levels, white blood cell count, and peripheral blood and bone marrow blasts. (Table 1)
  • A total of 87 (84%) patients had solid cancer (breast: 38, prostate: 14, head and neck: 9, gastrointestinal: 9, and other: 14).
  • Five patients had non-Hodgkin lymphoma, while three had Hodgkin lymphoma.
  • Eight patients had autoimmune disease.
  • The median latency period from prior disease to the onset of t-APL was 3.5 years (range: 0.4–26.2).

Table 1. Baseline characteristics

Efficacy

  • Patients receiving ATO/ATRA had the highest complete remission rate at 100%, while patients received ATRA only had the highest early death rate at 43%. (Table 2)
  • The patients receiving CTX/ATRA had the highest number of competing events in remission.
    • Two had relapses of the prior malignancy, two had infections, two had therapy-related acute myeloid leukemia, three had relapses of t-APL, one developed diffuse large B-cell lymphoma, and one had a competing event of unknown cause.
  • Of the patients receiving ATO/ATRA, one patient had relapse of the prior malignancy, one patient had an infection, and one suffered cardiopulmonary arrest during therapy.
  • One patient receiving CTX/ATO/ATRA and three receiving ATRA had relapses of the prior malignancy.
  • The 2-year event-free survival (EFS) rates were 78% (95% CI: 64–87) in patients treated with CTX/ATRA, 89% (95% CI: 64–97) in the ATO/ATRA group, and 95% (95% CI: 68–99) in the CTX/ATO/ATRA group. (Figure 1)
  • The estimated 2-year overall survival rates for patients receiving CTX/ATRA were 84% (95% CI: 71–92), 89% (95% CI: 64–97) for ATO/ATRA, and 95% (95% CI: 68–99) for CTX/ATO/ATRA. (Figure 1)
    • None of the patients treated with ATRA alone survived beyond one year.
  • When excluding death due to primary malignancy, the estimated 2-year modified EFS rate was significantly higher in patients treated with ATO-based therapy, including both ATO/ATRA and CTX/ATO/ATRA (95%; 95% CI: 82–99), when compared with patients treated with CTX/ATRA (78%; 95% CI: 64–87; p = 0.045). (Figure 2)
  • Cumulative incidence of relapse in intensively treated patients showed a strong trend towards a higher cumulative incidence of relapse after treatment with CTX/ATRA when compared with ATO-based regimens (p = 0.07).

Table 2. Response to induction therapy*

Figure 1. Event-free and overall survival

Figure 2. Event-free survival excluding death due to primary malignancy

Key conclusions

  • The distribution of clinical and biological characteristics in t-APL is comparable with what has been described in patients with de novo APL.
  • There was an excellent and sustained response, as well as favourable survival profile, following ATO-based regimens as first-line treatment.
  • ATO, when combined with ATRA or CTX/ATRA, is a feasible treatment and leads to better outcomes than CTX/ATRA alone.

References: 1. Ravandi F. Therapy-related acute promyelocytic leukemia. Haematologica 2011;96(4):493–5. 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. 3. Kayser S, Krzykalla J, Elliott MA, et al. Characteristics and outcome of therapy-related acute promyelocytic leukemia after different front-line therapies. Intl. Symposium on APL Abstracts 2017:CO033.