Phase III Trial of New Leukemia Treatment Yields "Remarkable" Results

A recent clinical trial has revealed that personalized treatment durations based on blood tests significantly improve survival and remission rates in CLL (Chronic Lymphocytic Leukemia), representing a major advancement in leukemia treatment.

In a phase III trial, researchers at the University of Leeds found that tailoring treatment to individual patients with the most common type of adult leukemia not only prolongs survival but also helps maintain remission.

The study was recently published in the New England Journal of Medicine and featured at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego.

The trial demonstrated that by regularly monitoring a patient's response through blood tests, therapy duration can be customized for each patient. This approach resulted in notable improvements in both progression-free and overall survival in patients with previously untreated CLL. Patients with poorer outcomes to standard treatments, like those with certain genetic mutations, saw an even stronger effect.

Adult patients were given a combination of drugs that blocked cancer growth for varied durations based on how quickly their disease responded.

The trial indicated that this approach significantly improved both progression-free and overall survival compared to standard CLL treatment, with more than 95% of patients remaining in remission three years after starting treatment.

The FLAIR study, a phase III randomized controlled trial for untreated CLL, was conducted in over 100 UK hospitals and supported by Cancer Research UK, Janssen Research & Development, LLC, and AbbVie Pharmaceutical Research and Development.

The study's lead author, Professor Peter Hillmen, stated that the treatment was not only effective at combating the disease but also well tolerated by patients. This ensured better outcomes and improved quality of life during treatment. The end of the treatment saw the majority of patients with no detectable leukemia in their blood or bone marrow.

Dr. Iain Foulkes, Executive Director of Research and Innovation at Cancer Research UK, expressed delight at the results of the FLAIR trial, emphasizing the importance of personalizing cancer treatment. He applauded the trial's ability to achieve this without resorting to frequent, potentially painful bone marrow tests.

Chronic lymphocytic leukemia, which typically affects those aged 55 and over, is a type of cancer affecting the blood and bone marrow. While it typically cannot be cured, it can be managed with treatment.

The FLAIR trial tested cancer growth blockers known as Ibrutinib and Venetoclax, usually given either consistently or for a similar fixed length, without tailoring to each patient's response. This might cause patients to either stop treatment prematurely or continue longer than required, increasing the possibility of relapse and treatment side effects.

Using regular blood and bone marrow monitoring, the FLAIR researchers were successful in tailoring the duration of I+V treatment for patients. Moreover, it was found that less invasive blood samples were as effective as bone marrows in determining the treatment duration.

The FLAIR trial, which began in 2014, included 1,509 CLL patients who were divided into four treatment groups.

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. Almost three-quarters were male, which was to be expected as CLL occurs more frequently in males. 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, 75 of which were on FCR, and 12 on I+V.

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

The patients on I+V underwent blood tests and bone marrows to monitor their response to treatment. The technique used is known as measurable residual disease (MRD) which allows clinicians to see the number of remaining cancer cells. The number of cells may be so small that the patient is asymptomatic. An MRD positive test result means that there are remaining cancer cells.

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

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 treated. FLAIR has been a huge collaborative effort over the last decade by the UK’s leading CLL specialists and by the hematology teams in over 100 hospitals throughout the UK. The participation of patient groups, individual patients, and their families was critical to delivering such progress, particularly through the challenges of the pandemic.”

The trial was co-ordinated by the Leeds Cancer Research UK Clinical Trials Unit at the University of Leeds. Deputy Director Professor David Cairns said: “The vision of the Leeds Cancer Research UK CTU is to improve the length and quality of survival for cancer patients on a worldwide scale. Our strategy to do this is to ensure that we build evidence to identify the correct treatment, for the correct duration, for the correct patient. FLAIR is a trial well aligned with our strategy, and reflects team science including clinicians, laboratory scientists, methodologies, and operational experts working together to deliver important trial results. None of this would be achieved without the selfless commitment of trial participants who contribute their time and data.”