A phase III trial at the University of Leeds has found that personalized treatment for the most common type of adult leukemia can extend patients' survival and maintain remission. This important research was recently published in the New England Journal of Medicine and was highlighted at the 65th American Society of Hematology (ASH) Annual Meeting & Expo in San Diego.

The data shows that by monitoring patient response with regular blood tests, treatment times can be tailored to each patient. In trials, this approach significantly improved progression-free survival and overall survival in patients with previously untreated chronic lymphocytic leukemia (CLL). The effects were greater in patients who responded less well to standard treatments, such as those with certain genetic mutations.

Personalized treatment methods and their effectiveness

Adult patients take a variety of drugs that block cancer growth for varying periods of time, depending on how quickly their disease responds.

The trial found that this approach significantly improved progression-free and overall survival compared with standard treatments for CLL, with 19 out of 20 patients going into remission three years after starting treatment.

The study, called FLAIR, is a phase III randomized controlled trial of untreated CLL and is being conducted at more than 100 hospitals in the UK. The study was funded by Cancer Research UK, Janssen Research & Development, LLC and AbbVie Pharmaceutical Research and Development.

Lead author Peter Hillmen, Professor of Experimental Hematology at the University of Leeds Medical School and Honorary Hematology Consultant at Leeds Teaching Hospitals NHS Foundation Trust, said: "Our findings suggest that for a subset of patients, treatments can be very effective for their disease and that they can be very successful. "It was well tolerated. This means patients in our trial had better outcomes and also enjoyed a better quality of life during treatment. Most patients who received the new combination had no detectable leukemia in their blood or bone marrow after treatment, which is better than previous treatments, which is very encouraging."

Research findings and future implications

Dr Iain Foulkes, Cancer Research UK's executive director of research and innovation, said: "We are delighted to see these results from the FLAIR trial, which demonstrate the importance and effectiveness of tailoring cancer treatments to individual patients. Not only that, but the trial has also found a way to reduce the need for frequent Methods of conducting bone marrow tests, which are more invasive and painful for patients. The combined efforts of researchers, health care providers, funders and enthusiastic patients and their families point to a new standard of care that will make real progress in the fight against leukemia."

Chronic lymphocytic leukemia is a cancer that affects the blood and bone marrow. There is usually no cure, but it can be managed with treatment. More than 9 in 10 people were 55 and older at the time of diagnosis.

Current treatments include chemotherapy, immunotherapy or cancer growth-blocking drugs.

The cancer growth blockers being tested in the FLAIR trial are Ibrutinib and Venetoclax (I+V). The two drugs, known by the brand names Imbruvica and Venclexta, are often given continuously or at fixed times rather than tailored to each patient's response. This means that many patients may stop treatment prematurely, not fully benefit from treatment, or continue treatment longer than necessary. This may lead to an increased chance of leukemia recurrence and/or side effects of treatment.

Researchers at FLAIR aim to discover whether it is possible to personalize I+V treatment times for patients based on regular blood sampling and/or bone marrow sampling, and whether this approach is as effective as or better than standard care (FCR).

Through this regular blood and bone marrow monitoring, researchers can gain a more timely understanding of a patient's response to I+V, meaning the duration of I+V treatment can be tailored to each patient's specific circumstances. Additionally, the researchers found that determining treatment duration based on less invasive, faster blood samples was as effective as using bone marrow, which can cause pain to the patient and sometimes requires sedation.

Experimental design and results

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

This part of the FLAIR trial compared two groups of patients, with 260 patients receiving I+V and 263 patients receiving standard care, FCR. Nearly three-quarters of patients are male, which is expected because CLL occurs more often in men. The average age is 62 years, and slightly more than one-third of the patients have advanced disease.

At the end of this phase of the trial, 87 patients had progressed, of whom 75 had received FCR and 12 had received I+V.

So far, 34 patients have died during the trial. 25 of them received FCR treatment, and only 9 received I+V treatment.

Patients receiving I+V received blood and bone marrow tests to monitor their response to treatment. The technology used is called measurable residual disease (MRD), which allows clinicians to see how many cancer cells are left. The number of cells may be so low that the patient has no symptoms. A positive MRD test result means that residual cancer cells are present.

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

Professor Hilman said: "The results of the FLAIR trial, led by the Leeds Cancer Research UK Clinical Trials Group at the University of Leeds, are outstanding and herald a change in the way chronic lymphocytic leukemia is treated. "FLAIR is the result of a joint effort over the past decade by the UK's leading experts in chronic lymphocytic leukemia and hematology teams at more than 100 hospitals across the UK. The engagement of patient groups, individual patients and their families is critical to making such progress, especially amid the challenges of a pandemic.

The trial is coordinated by the Leeds Cancer Research UK Clinical Trials Group at the University of Leeds. Professor David Cairns, deputy director, said: "Leeds Cancer Research's vision is to improve the survival and quality of life of cancer patients globally. To this end, our strategy is to ensure that evidence is accumulated to determine the right treatment, and the right time for patients. FLAIR "This is a trial that is highly consistent with our strategy and embodies team science, including clinicians, laboratory scientists, methodologists and operational experts working together to achieve important trial results. None of this would be possible without the dedication of trial participants, their time and data."

Compiled source: ScitechDaily