Head-to-head trial of BTKi in CLL: ASCO
First results of a head-to-head trial of acalabrutinib (Aca) versus ibrutinib (Ib) in previously treated chronic lymphocytic leukaemia show Aca had non inferior PFS, less cardiotoxicity and fewer discontinuations due to adverse events.
The findings were presented this week at ASCOs annual scientific meeting and mark the first open-label, randomised, non inferiority, phase 3 trial to compare the two agents.
Some 533 previously treated CLL patients with del(17p) or del(11q) from several international sites, including Australia, were randomised to receive oral Aca 100 mg BID or Ib 420 mg QD until progression or unacceptable toxicity.
The investigators, including Professor John Seymour from the Peter MacCallum Cancer Centre & Royal Melbourne Hospital, reported that Aca was non inferior to Ib with a median PFS of 38.4 months in both arms (HR 1.00; 95% CI 0.79–1.27) at a median follow up 40.9 months.
Meanwhile Aca was statistically superior to Ib in all-grade atrial fibrillation incidence (9.4% vs 16.0%; P=0.023).
Among the other secondary endpoints, incidences of grade ≥3 infection (Aca: 30.8%, Ib: 30.0%) and Richter transformation (Aca: 3.8%, Ib: 4.9%) were comparable between arms, report investigators.
And among any-grade AEs in ≥20% of pts in either arm, Aca was associated with a lower incidence of hypertension (9.4%, 23.2%), arthralgia (15.8%, 22.8%), and diarrhoea (34.6%, 46.0%) but a higher incidence of headache (34.6%, 20.2%) and cough (28.9%, 21.3%).
AEs led to treatment discontinuation in 14.7% of Aca- vs 21.3% of Ib-treated pts. Among any-grade events of clinical interest, cardiac, hypertension, and bleeding events were less frequent with Aca, investigators said.
Median OS was not reached in either arm (HR 0.82 [95% CI 0.59–1.15]), with 63 (23.5%) deaths in the Aca arm and 73 (27.5%) in the Ib arm.
EBV-positive lymphoma with MTX
Lymphoproliferative disorders (LPD) are a rare but significant complication of long-term methotrexate use in patients with rheumatoid arthritis and further complicated by the Epstein-Barr virus (EBV), a new paper shows.
Two Australian case studies of EBV-positive LPD highlight the interplay between RA, LPD, EBV and MTX use.
“In Case 1, the association between MTX and lymphoma was strong as evidenced by the 20-year duration of MTX use and subsequent clinical improvement once MTX was ceased,” the report said.
“In comparison, Case 2 had a shorter duration of MTX (eight years) but showed evidence of high EBV load in lung parenchyma at autopsy.”
“Our cases highlight the need to consider methotrexate reduction in rheumatoid arthritis patients whose disease has been well controlled for many years,” the authors said
Undiagnosed haemochromatosis in Australia
Experts in Australia are calling for a haemochromatosis screening program to pick up more than 100,000 people estimated to be undiagnosed with the condition following recent UK findings identifying higher risks of liver disease, arthritis and other chronic conditions in people with iron overload.
Murdoch Children’s Research Institute and Medical Director of the Victorian Clinical Genetics Service, Professor Martin Delatycki, said the research, led by the University of Exeter, projected that more than 7% of men with two copies of the faulty haemochromatosis gene develop liver cancer by age 75, compared to just 0.6%in the general population.
The team have also previously reported that having the double faulty gene quadruples the risk of liver disease and doubles the risk of arthritis and frailty in older age groups. It also causes higher risk of diabetes and chronic pain.
According to Professor Delatycki even in cases where iron stores were only mildly elevated patients benefit from venesections and are unlikely to develop chronic conditions associated with iron overload when treated early.
Haemochromatosis Australia president, Dr Dianne Prince added that while the condition can be managed with early diagnosis ‘sadly’ people with significant health problems caused by late diagnosis continue to present.
“It’s quite common for people with these symptoms to think they’re actually iron deficient and take supplements, not knowing it’s the last thing they need. We urge people to get their iron levels checked before taking iron supplements or iron fortified foods,” she added.