New personalized therapy improves survival of CLL leukemia patients, phase 3 trial finds

Personalized treatment for the most common form of adult leukemia helps patients survive longer and stay in remission, a phase 3 trial shows.

The essay, carried out by the University of Leeds, is published in the New England Journal of Medicine and was presented at the 65th Annual Meeting and Exhibition of the American Society of Hematology (ASH) in San Diego. The journal article is titled “Therapy for Chronic Lymphocytic Leukemia Guided by Measurable Residual Disease.”

The data shows that the duration of treatment can be individualized for each patient using regular blood tests to monitor their response. In the trial, this approach resulted in significant improvements in progression-free survival and overall survival in patients with previously untreated chronic lymphocytic leukemia (CLL). The effect was stronger in patients who performed worse with standard treatments, such as those with certain genetic mutations.

Adult patients received a combination of drugs that blocked cancer growth for varying lengths of time depending on how quickly their disease responded.

The trial found that this approach significantly improved progression-free survival and overall survival compared to standard CLL treatment, with more than 19 out of 20 patients in remission three years after starting treatment.

The study, named FLAIR, is a phase 3 randomized controlled trial in untreated CLL, taking place in more than 100 hospitals across the UK.

Lead author Peter Hillmen, Professor of Experimental Hematology at the University of Leeds Medical School and Honorary Consultant Haematologist at Leeds Teaching Hospitals NHS Trust, said: “Our results show that, for this group of patients, the treatment is very effective in fighting their disease and is well tolerated by them.

“This means that patients in our trial had better outcomes while enjoying a better quality of life during their treatment. Most patients treated with the new combination have no detectable leukemia in the blood or bone marrow at the end of treatment, which is better than with previous treatments and is very encouraging.

Dr Iain Foulkes, executive director of research and innovation at Cancer Research UK, said: “We are delighted to see these results from the FLAIR trial which show the importance and effectiveness of adapting treatment of cancer to each patient. the trial found a way to do this without requiring frequent bone marrow tests that are more invasive and can be painful.

“The collaborative effort that led to this trial, involving researchers, healthcare professionals, funders and dedicated patients and their families, points to a new standard of care that could enable real progress against leukemia .”

Chronic lymphocytic leukemia is a type of cancer that affects the blood and bone marrow. It usually cannot be cured, but can be managed with treatment. More than nine in ten people are aged 55 and over at the time of diagnosis.

Current treatments include chemotherapy, immunotherapy or cancer growth blockers.

The FLAIR trial tested cancer growth blockers called Ibrutinib and Venetoclax (I+V). Also known by the brand names Imbruvica and Venclexta, these are usually given either continuously or for the same fixed duration rather than tailored to each patient’s response. This means that many patients may stop treatment too early and not get the full benefit from their treatment or may not continue treatment for longer than necessary. This could lead to a greater risk of relapse of their leukemia and/or side effects of treatment.

FLAIR researchers sought to find out whether it was possible to personalize the duration of I+V treatment for patients based on regular blood and/or bone marrow sampling, and whether this was as effective or better than treatment standard (FCR).

This regular monitoring of blood and bone marrow gave researchers a more up-to-date picture of how patients were responding to I+V and allowed the duration of I+V treatment to be tailored to each patient. . Additionally, basing treatment duration on less invasive and faster blood draws was found to be just as effective as using bone marrow, which can be painful and sometimes requires sedation.

FLAIR was launched in 2014 and enrolled 1,509 CLL patients. They were randomized into four treatment groups, each receiving a different treatment.

This part of the FLAIR trial compared two of the groups, placing 260 patients on I+V and 263 on the standard treatment, known as FCR. Nearly three-quarters were men, which was expected since CLL occurs more frequently in men. The average age was 62 and just over a third had advanced disease.

At the end of this stage of the trial, 87 patients had seen their disease progress, including 75 on FCR and 12 on I+V.

To date, 34 of these patients have died during the trial. Among them, 25 were treated by FCR and only nine by I+V.

Patients on I+V had blood and bone marrow tests to monitor their response to treatment. The technique used is known as measurable residual disease (MRD), which allows clinicians to see the number of cancer cells remaining. The number of cells may be so small that the patient is asymptomatic. A positive MRD test result means that cancer cells remain.

The research team now hopes that this more personalized treatment approach, guided by blood test monitoring, will be adopted as the new standard of care for patients requiring first-line treatment for CLL.

Professor Hillmen said: “The results of the FLAIR trial, led by the Leeds Cancer Research UK Clinical Trials Unit at the University of Leeds, are exceptional and herald a change in the way chronic lymphocytic leukemia will be processed. FLAIR has been a huge partnership effort over the last decade by the UK’s leading CLL specialists and hematology teams in over 100 hospitals across the UK. The participation of patient groups, individual patients and their families has been essential to achieving such progress, especially in the face of the challenges of the pandemic.

The trial was coordinated by the Leeds Cancer Research UK clinical trials unit at the University of Leeds. Deputy Director, Professor David Cairns, said: “The vision of Leeds Cancer Research UK CTU is to improve the length and quality of survival for cancer patients globally. Our strategy to achieve this is to ensure we build evidence to identify the right treatment, for the right duration, for the right patient.

“FLAIR is a trial well aligned with our strategy and reflects the science of a team including clinicians, laboratory scientists, methodologists and operational experts working together to deliver important trial results. None of this would be achieved without the selfless commitment of the trial participants who give up their time. and data.”