Ann Robinson’s research reviews—16 March 2023

AML: markers on the road to cure?

Acute myeloid leukaemia (AML) is a cruel disease: 85% of those diagnosed will be dead within five years. Treatment usually consists of chemotherapy to achieve remission, often followed by stem cell transplant for those at highest risk of relapse. Stem cell transplant greatly increases the chance of survival and can be curative, but having a transplant is no picnic and it needs to be reserved for those most likely to benefit.

This study of adults with AML in first remission after chemotherapy, but before transplant, found that those with DNA variants FLT3-ITD and NPM1 in their blood had significantly higher rates of relapse and poorer three year survival compared with those without the markers (validation cohort difference 47% and −24%). This is an example of using genetic profiling mid-treatment to guide next steps, but much larger clinical data sets are needed to show whether this approach actually translates into more saved lives.

JAMA doi:10.1001/jama.2023.1363

Ulcerative colitis: an anti-inflammatory that doesn’t suppress immunity

Ulcerative colitis is a growing and incurable condition. Fresh options are needed for when conventional therapy fails. Olamkicept, a selective inhibitor of the cytokine interleukin 6, increased the likelihood of a clinical response in this Chinese study of 91 people with ulcerative colitis, though only at a higher dose (response rates at 12 weeks with olamkicept 600 mg v olamkicept 300 mg v placebo were 59%, 43%, and 34%). Unlike many other drugs used in ulcerative colitis, olamkicept is anti-inflammatory without being immunosuppressant. It’s not a perfect study: 94% of patients hadn’t had biologic therapies, which suggests that their ulcerative colitis was relatively mild and results may not translate to those with severe disease; and the sample size was small with a disproportionately high dropout rate in the placebo group (23.3%) compared with the olamkicept 300 mg group (6.5%).

JAMA doi:10.1001/jama.2023.1084

One size doesn’t fit all

Is it better to offer frail people with non-ST segment elevation myocardial infarction (NSTEMI) invasive treatment (coronary angiography and revascularisation if feasible) or conservative medical treatment, with coronary angiography only for recurrent ischaemia? In this Spanish study a strategy of routine invasive treatment versus conservative care in 167 older, frail patients with NSTEMI didn’t have a significant impact on the number of days alive and out of hospital (284 v 312 days), all-cause mortality, number of readmission days, or further ischaemic cardiac events.

This is in stark contrast to previous studies that included non-frail and younger patients, in whom invasive treatment does seem to be superior. This is only a small study and needs to be interpreted with care: it didn’t include the most clinically unstable patients, and 11% of those in the conservative care group who were deteriorating were crossed over to invasive management. But it definitely warrants further study to test the opposite hypothesis, namely that watchful waiting and evaluation may be preferable to invasive treatment in frail, older people.

JAMA Intern Med doi:10.1001/jamainternmed.2023.0047

Once bitten, twice shy

Does having covid-19 protect you against further infections, symptoms, and severe disease? How long does the protection last, and does it matter which variant you had? We need to know the answers to predict future epidemics, design sensible policies to limit transmission, and work out when to offer vaccination.

This ambitious systematic synthesis of 65 studies found that protection from past infection was high from ancestral alpha, beta, and delta variants, but substantially lower for the omicron variant. This chimes with what many of us observed in practice. Protection against reinfection wore off more rapidly with omicron than other variants (36% v 78% at 40 weeks). On the plus side, prior infection with all variants was highly protective against severe disease (hospital admission and death) and remained at around 90% even at 40 weeks. The findings support the idea that having a documented infection is equivalent to being vaccinated with two doses of an mRNA vaccine (as the EU covid certificate recognised, but the US didn’t).

Lancet doi:10.1016/S0140-6736(22)02465-5

The times they are a-changin’

Standard treatment for drug-susceptible pulmonary tuberculosis (TB) over the past 40 years has been a six month rifampicin-based regimen. Cure rates are over 95% within clinical trials, but often much lower in the real world. Incomplete treatment leads to more drug resistant strains, and TB remains a global scourge. The shorter the course, the more likely it is to be completed.

This neat study found that initial treatment for TB with an eight week bedaquiline-linezolid (and isoniazid, pyrazinamide, and ethambutol) regimen was non-inferior to a 24 week standard treatment (rifampicin and isoniazid for 24 weeks with pyrazinamide and ethambutol for the first eight weeks) with respect to clinical outcomes with no difference in safety. The primary outcome of death, ongoing treatment, or active disease at week 96 was 5.8% versus 3.9%. Another eight week combination including rifampicin and linezolid didn’t show non-inferiority (primary outcome 11.4%). As you’d expect, participants were happier with the eight week option. Further studies to test other drug combinations and extend the study population would be useful now.

N Engl J Med doi:10.1056/NEJMoa2212537