The vast majority of patients (approximately 75%) with newly diagnosed CLL do not need treatment at the time of initial diagnosis. The standard management for such patients consists of seeing an oncologist on a periodic basis to perform a physical exam and laboratory testing (generally once every 3-6 months) until the disease progresses, at which point treatment is usually initiated (“watch and wait” strategy).
However, a subset of newly diagnosed CLL patients has high-risk disease at the time of diagnosis. In the absence of treatment, these patients may experience rapid worsening of their CLL. Additionally, they may be at a high risk of clinical complications such as serious infections and non-hematologic malignancy.
We will use the CLL-International Prognostic Index (CLL-IPI) to identify newly diagnosed CLL patients who have high risk of disease progression, who may be at risk for these adverse clinical consequences. The CLL-IPI consists of five easily obtainable variables that are each associated with a shorter time to first therapy; these include age, serum beta-2 microglobulin, Rai stage, IGHV mutation status, and the presence of del17p on FISH testing. Using a weighted average for each of these variables, the total CLL-IPI score will then be computed for all patients. Patients with a high risk (score 4-6) and very high risk (score 7-10) CLL-IPI will be randomly assigned to receive treatment with acalabrutinib (a second generation Bruton tyrosine kinase inhibitor) alone or in combination with obinutuzumab (monoclonal antibody against CD20 approved by the FDA for the treatment of CLL). Treatment will continue for at least 2 years or until the patient achieves minimal residual disease negative complete remission, whichever occurs later. Patients with low risk (score 0-1) and intermediate risk (score 2-3) CLL-IPI will be observed without any specific therapy, to monitor time to first treatment and development of clinical complications.
The trial is currently open to enrollment at Mayo Clinic (in Rochester, MN, Scottsdale, AZ, and Jacksonville, FL). For further information about the inclusion/exclusion criteria for this trial, please refer to https://clinicaltrials.gov/ct2/show/NCT03516617. If you would like to make an appointment to see a CLL specialist, please contact the appropriate Mayo Clinic site to be enrolled (https://www.mayo.edu/research/clinical-trials/cls-20425269).