Abstract: EP616

Type: e-Poster

Presentation during EHA25: All e-Poster presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Background

The introduction of all-trans retinoic acid (ATRA) in the mid-1980s revolutionized the management of acute promyelocytic leukemia (APL). As a result, APL is a largely curable disease when diagnosed timely and managed promptly. The high event-free survival rates in APL entail research on survival expectations for each additional year survived, conditional on being alive at the start of that year—ie, conditional survival (CS). A dynamic prediction of prognosis at a specified time from diagnosis counteracts the pessimistic view of survival estimates measured at diagnosis due to patients dying within the first few years post-diagnosis. At present, statistics on CS in APL are lacking.

Aims

Here, in this nationwide, population-based study, we assessed conditional relative survival (CRS)—which is the CS of patients corrected for the expected survival of comparable groups from the general population—among adult APL patients diagnosed in an era where anthracycline-based chemotherapy with concurrent ATRA was the standard of care.

Methods

We selected all adult (≥18 years) patients with APL diagnosed in the Netherlands between 1989-2017 from the nationwide Netherlands Cancer Registry, with survival follow-up through 2019. Five-year relative survival (RS) was calculated at diagnosis and for each additional year survived up to 10 years post-diagnosis (ie, conditional 5-year CRS). RS is the ratio of the patients’ overall survival to the expected survival of an age-, sex-, and period-matched group from the general population. All analyses were performed for the overall cohort and stratified by sex, age at diagnosis (18-40, 41-60, and >60), and calendar period of diagnosis (1989-2000 and 2001-2017). Five-year CRS was truncated at 5 years post-diagnosis for patients above age 60 due to limited patients numbers beyond that year. Excess mortality (EM), as compared to an age-, sex-, and period-matched group from the general population, is considered minimal when RS exceeds 95%. Statistical significance between subgroups in 5-year RS at diagnosis and CRS estimates were assessed using likelihood ratio tests. A P<0.05 indicated statistical significance.

Results

Our analytical cohort included 746 adult APL patients (median age, 53 years; 47% males; 69% diagnosed during 2001-2017). The age distribution was 26, 37, and 37% across the three age groups. Overall, 5-year RS at diagnosis was 60% (Fig 1A). Five-year CRS increased with each additional year survived from diagnosis up to 95% at 10 years post-diagnosis, which was already reached from the fifth year (Fig 1A). Five-year RS at diagnosis and CRS estimates did not differ according to sex (P>0.05; Fig 1B). However, 5-year RS at diagnosis decreased with older age (P<0.001; Fig 1C). The CRS estimates across the three age groups became smaller, albeit remained persistent for patients above age 60. For patients up to age 60, 5-year RS at diagnosis was already comparatively high. EM in this age group became minimal after 4 to 5 years post-diagnosis Five-year RS at diagnosis increased over the calendar periods studied (P<0.001; Fig D). The period differential became smaller over time.

Conclusion

Adult patients with APL up to age 60 experience minimal EM at 4 to 5 years post-diagnosis, whereas those above age 60 have consistent poorer survival compared to the expected survival of similar groups from the general population. Therefore, optimism is centered on new treatment options to reduce EM. Also, more intense follow-up care might be considered within the first 5 years post-diagnosis, especially in older patients.

Session topic: 04. Acute myeloid leukemia - Clinical

Keyword(s): Acute promyelocytic leukemia, Epidemiology, Survival