EVOLVE trial for high risk chronic lymphocytic leukemia - CLL patients will test an early treatment intervention Vs watch and wait

[CLLerinOz]

'The goal of the S1925 [EVOLVE] trial is to find out if early treatment can help people with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) live longer and have a better quality of life.'

'Studies show that early treatment using older chemotherapy drugs doesn’t help people live longer or better compared to later treatment. In this trial, researchers want to find out if early treatment with newer, more targeted cancer drugs will help patients live longer and improve their quality of life. To learn this, they will compare outcomes in early and later treatment groups.'

swog.org/s1925

Eligibility criteria and trial locations are available on the clinicaltrials.gov website:

'Testing the Effects of Early Treatment With Venetoclax and Obinutuzumab Versus Delayed Treatment With Venetoclax and Obinutuzumab for Newly Diagnosed Patients With High-Risk Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Who Do Not Have Symptoms, the EVOLVE CLL/SLL Study'

clinicaltrials.gov/ct2/show...

SOME BACKGROUND:

Most people who are diagnosed with CLL are told that their condition will be managed initially for a period of time without treatment. That period is called "Watch & Wait" or "Watchful Waiting". For some people, the watch and wait period can extend to decades if they have a slow, fairly stable form of CLL.

' . . . about 80% of patients with CLL show no symptoms at diagnosis and therefore do not meet the medical criteria for initiating treatment. '

Now, especially with the advent of time limited combination therapies using targeted therapies, the appropriateness of watch and wait, particularly for high risk CLL patients whose disease usually progresses more quickly, has started to be questioned.

There are some obvious advantages to time limited treatment with targeted therapies. They can offer patients the benefit of a period of treatment which can lead to undetectable or unmeasurable minimal residual disease (uMRD). This can be followed, hopefully, by a long period off medication before another period of treatment might be required, if at all.

In particular, early treatment for high risk patients could help to prevent clonal evolution that might lead to the development of mutations which would make the patient more susceptible to drug resistance and more aggressive disease progression.

There have been a couple of earlier trial attempts to determine whether it's worth beginning early treatment for people with high risk markers, but they have been inconclusive. One that has reported significant results is the CLL12 trial. However, it is not testing a time limited therapy and looks at Ibrutinib monotherapy VS a placebo .

'In the largest clinical trial of patients with asymptomatic CLL—the ongoing CLL12 study—515 patients with intermediate-, high-, or very high-risk asymptomatic CLL are receiving ibrutinib or placebo for up to 5 years or until their disease progresses.1 Although the study is currently ongoing, data from the halfway point suggest that patients receiving ibrutinib may have fewer CLL-related events than those receiving placebo.1 Notably, and unlike what was previously seen with chemotherapy, both placebo and ibrutinib groups are reporting a similar number of side effects.1'

Now, another trial, the EVOLVE trial, is recruiting patients in North America. It is for 'patients who have previously untreated early-stage CLL at high or very high risk for disease progression.1,2 Patients will receive venetoclax and the immunotherapy obinutuzumab, either at diagnosis or after their disease has progressed, to determine whether early treatment affects their life expectancy.1'

conquer-magazine.com/web-ex...

See also our previous post about the CLL12 trial, which contains this statement by Prof John Seymour:

"Given the observation that clonal evolution, including acquisition of the biologically adverse features, such as TP53mut and complex karyotype, can emerge between diagnosis and initiation of first treatment, well-designed early intervention trials should continue to be pursued. However, careful selection of outcome measures that consider the longitudinal nature of the disease is critical."

healthunlocked.com/cllsuppo...

Might there be a study of a BTK inhibitor plus Venetoclax as an early treatment for high risk patients at some time in the future? Time will tell.

Note: This is an unlocked post for wider audience reach. CLL Support community members can comment to this locked post version: healthunlocked.com/cllsuppo...