Patients with acute promyelocytic leukaemia (APL) treated with frontline all-trans retinoic acid and arsenic trioxide (ATRA/ATO) who survive the acute phase achieve long-term survival indistinguishable from that of the general population.
An Italian study, published as a letter in Nature [link here], analysed mortality patterns in 249 long-term survivors with low- to intermediate-risk APL treated with ATRA/ATO within the GIMEMA APL0406 and APL0618 studies.
The median follow-up was 5.6 years for APL0406 and 2.8 years for APL0618.
The study found two deaths in each of the ATRA/ATO treated patients from the APLO cohorts – “essentially mirroring the 3.95 deaths predicted on the basis of age, sex, geographic distribution and follow-up time.”
“In APL0406, the standardised mortality ratio was 0.89 (95% CI: 0.10 to 3.22), indicating a mortality pattern consistent with that expected for the general population. In APL0618, the standardised mortality ratio was 1.17, (95%CI: 0.14 to 4.21), again showing no deviation from the mortality anticipated for a demographically matched reference population,” it said.
“The resulting standardised mortality ratio for the pooled cohort was 1.01 (95%CI: 0.27 to 2.59), confirming the absence of any measurable excess mortality among long-term survivors treated with ATRA and ATO.”
They said their findings confirm that APL survivors treated with ATRA/ATO do not experience measurable excess mortality and can anticipate a long-term prognosis equivalent to individuals without haematologic malignancies.
“Placed in historical context, this outcome is extraordinary. APL was long regarded as the most lethal variant of acute leukemia, primarily due to its rapid onset and life-threatening coagulopathy.”
It said anthracycline-based chemotherapy improved remission rates, but long-term toxicity and relapse remained significant concerns.
“The introduction of ATRA revolutionised treatment by enabling differentiation of leukaemic blasts, while the addition of ATO eliminated the need for cytotoxic chemotherapy for most patients and drastically improved cure rates.”
The investigators said the remaining challenges in APL were to reduce early mortality from haemorrhagic complications, diagnostic delays, or failure to initiate ATRA promptly.
“Strategies focused on rapid recognition of APL, immediate administration of ATRA even when diagnosis is only suspected, and optimised supportive care are therefore essential.”