A drug crucial for the emergency management of acute promyelocytic leukemia (APL) simply isn’t stocked by many US hospitals, according to a recent report in the Journal of the National Comprehensive Cancer Network.
The drug — all-trans retinoic acid (ATRA 10-mg tablets, TEVA) — is a fixture in the treatment of new-onset APL, which is “recognized as a true hematologic emergency,” the investigators write.
Although APL is considered the most curable form of acute myelogenous leukemia (AML), 30-day mortality can be as high as 25%, due to severe disease-related complications, namely the serious blood clotting condition disseminated intravascular coagulation (DIC).
Given the concerning early mortality rate in APL, the National Comprehensive Cancer Network (NCCN) recommends that patients suspected of having APL receive ATRA within 24 hours to prevent or mitigate DIC.
However, according to the new analysis, less than one third of US hospitals surveyed stock ATRA, which is “why guidelines may not be followed.”
Senior author Dale Bixby, MD, PhD, a leukemia specialist at the University of Michigan in Ann Arbor, told Medscape Medical News that he hopes these findings will increase awareness about the importance of ATRA in managing APL and will spur pharmacists and hematologists to action.
However, Bixby noted, even with the NCCN recommendations, the use of ATRA as a frontline therapy for APL remains off label, which presents a challenge: Manufacturers can’t promote the indication or design programs to make the drug’s off-label use more affordable.
“Our pharmacy program at the University of Michigan Health System has recognized” the problem and has taken “steps locally and regionally to ensure that trainees are aware of APL and the need for this medication,” said Bixby, who has been working to raise awareness of the issue for several years.
Leukemia specialist James Mangan, MD, PhD, of the University of California, San Diego, agreed about the need for hospitals to stock this medication. This study is “a clarion call to action to lobby for inclusion of ATRA on the formularies of all hospitals who encounter acute leukemia patients, no matter whether they are a referring or treating center,” Mangan, who sits on the NCCN AML guideline committee but was not involved in the analysis, said in a press release.
To determine the availability of ATRA at US hospitals, Bixby and colleagues surveyed inpatient pharmacists at 120 randomly selected hospitals, each with 100 beds or more. The investigators chose hospitals in six states — Washington, Arizona, Missouri, Georgia, Massachusetts, and Michigan — to represent the nation.
Overall, just 31% reported having ATRA in stock. Of the hospitals that treat acute leukemia, 58% had ATRA, while only 14% that refer patients elsewhere for treatment had ATRA on hand.
The authors found no difference in ATRA availability based on hospital size, but academic centers were more likely to carry it than nonacademic hospitals (53% vs 35%; P = .08). In terms of availability by state, Washington had the highest percentage of hospitals carrying ATRA, at 65%, while Massachusetts and Missouri had the lowest, at 21% and 20%, respectively.
The authors noted the main reasons for the lack of ATRA availability included the drug not being requested recently, the pharmacist’s lack of familiarity with the agent, and the facility relying on other hospitals to provide it.
Another notable reason, however, may simply be that APL is rare — representing just 7.4% of all AML cases — and ATRA is expensive, with an average wholesale price of almost $3000 for 100 tablets.
Still, “the lack of immediate availability of ATRA at 42% of centers who treat acute leukemia [is] shocking and sobering,” Mangan said. “Furthermore, given that transfers from referring centers often take days due to bed availability issues, the lack of availability of ATRA at 86% of referring centers is a truly dangerous situation.”
No funding source was reported. The investigators have disclosed no relevant financial relationships.
J Natl Compr Canc Netw. 2021;19:1272–1275. Full text
M. Alexander Otto is a physician assistant with a master’s degree in medical science. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape and is an MIT Knight Science Journalism fellow. Email: [email protected].
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