News in brief: CAR T therapy for indolent lymphomas; Dabigatran resistant to reversal agent; DLBCL trial criteria too restrictive

CAR T therapy offers promising results in indolent lymphomas

The CAR T-cell therapy axicabtagene ciloleucel, or axi-cel, yielded high response rates and was well tolerated in a phase 2 study of patients with relapsed/refractory indolent non-Hodgkin lymphoma.

Among a total of 104 patients, the overall response rate to the therapy was 92%, and the complete response rate was 76%. Those with follicular lymphoma had overall and complete response rates of 94% and 80%, respectively, while those with marginal zone lymphoma – though only representing 20 total patients – had rates of 85% and 60%, respectively.

The responses appeared durable; after 17.5 months of follow-up, the median duration of response had not yet been reached. In patients with follicular lymphoma, responses were ongoing in 78% of those with a CR.

“The safety profile was manageable and reversible, and appeared to be at least similar to that of axi-cel in aggressive lymphomas,” said Dr Caron Jacobson, of the Dana-Farber Cancer Institute in Boston, who presented the results.

Axi-cel is currently indicated in the UK for treatment of adult patients with relapsed/refractory large B-cell lymphoma.

Dabigatran resistant to reversal agent

A Sydney man admitted to hospital with abdominal pain and acute kidney injury has recorded the highest dabigatran concentration in the medical literature, report haematologists at St Vincent’s hospital.

The 64-year-old had significant coagulopathy, which increased despite administration of the recommended dose of idarucizumab signalling resistance to the reversal agent.

Writing in Internal Medicine Journal Dr Helen Cashman and colleagues said the patient, who had been taking dabigatran 110mg daily for atrial fibrillation management, had a creatine level of 209 μmol/L (reference range 60–100 μmol/L) when he presented to St Vincent’s Hospital.

His last dabigatran dose was reportedly taken some 3–4 hours before presentation and he’d also been taking other medications including amiodarone, furosemide and ramipril.

With an elevated dabigatran concentration of 2230 ng/mL (RR approximately 75–240 ng/mL), doctors suspected potential inhibition of the P-glycoprotein efflux transporter by amiodarone or uraemia causing increased absorption and decreased clearance with continued use of dabigatran

They say closer coagulation monitoring and further idarucizumab doses are required in cases with significantly elevated dabigatran concentrations, particularly when there is kidney dysfunction, in emergency situations.

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 DLBCL trial criteria have become too restrictive

Phase III front-line DLBCL trial criteria have become increasingly restrictive over the last three decades, say Melbourne haematologists and researchers arguing that the practice may impact generalisability of recent trial results and will likely limit recruitment to ongoing studies.

The findings are based on an analysis of 42 first-line phase III DLBCL RCTs from recent years and dating back to 1990. Assessing changes to 31 individual eligibility criteria over the period, investigators say the presence of 15 increased significantly over time.

The total number of criteria per study also increased over time [median Era 1: 14·5, interquartile range (IQR) 12·6-16·4; Era 2: 21, 18·8-23·3; Era 3: 23, 21-25; P < 0·001].

Investigators say the changes have led to a ‘diminishing proportion’ of trial‐eligible patients, with less than 50% of patients from the group’s institutional database eligible for modern‐era studies.

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