When patients are diagnosed with chronic lymphocytic leukemia (CLL), they may not begin treatment right away. Early-stage patients with no symptoms and minimal changes in their blood counts are usually managed with a watch-and-wait approach (a.k.a. active surveillance) where they receive regular monitoring to determine if their disease is stable or starting to progress. However, within this group of early-stage patients, there may be some who are at higher risk of progression than others. The CLL International Prognostic Index (CLL-IPI) combines clinical, biological, and genetic information to further assess a patient’s risk of disease progression and death.
In this interview, our own Dr. Brian Koffman spoke with Dr. Neil Kay, a Professor of Medicine and a hematologist at Mayo Clinic, and Dr. Sameer Parikh, a hematologist and oncologist at the Mayo Clinic in Rochester, MN. They discussed why early-stage patients usually do not receive treatment and how that paradigm may be changing with the availability of new targeted therapies and better prognostic markers.
- Early studies showed that treating early-stage patients did not prolong their survival and possibly led to more side effects. However, the standard therapies of the time were chemotherapy drugs which are harsh and hard for patients to tolerate.
- Since these trials were conducted, there have been two major changes:
- Novel targeted therapies that are both effective and better tolerated have been approved.
- Clinicians are better able to identify patients at high risk of progression through tools such as the CLL-IPI.
- These changes have researchers looking to re-evaluate the question: Does starting treatment earlier (before symptoms start) prolong survival?
- Two ongoing clinical trials are trying to determine whether early treatment with different targeted therapies can help get patients into remission and prolong survival.
- Dr. Parikh is currently conducting a clinical trial with early-stage patients who do not need treatment right away but have a high or very high CLL-IPI risk score.
- These patients will receive either acalabrutinib alone or acalabrutinib + obinutuzumab.
- Acalabrutinib is just as effective as ibrutinib but with fewer side effects.
- The main outcome that researchers will be looking at is measurable residual disease (MRD) status after 2 years to see if early treatment can get patients into remission.
- They will also be looking at how often patients develop side effects such as infections or other secondary cancers.
- More information on participating in this trial can be found here: Acalabrutinib With or Without Obinutuzumab in Treating Patients With Early-Stage Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
- Another clinical trial of interest is the EVOLVE study, which is looking at the combination of venetoclax + obinutuzumab for treating early-stage high-risk patients.
- Patients will be randomized to receive venetoclax + obinutuzumab starting either around the time of diagnosis or when symptoms develop (which is when treatment would normally start)
- More information on participating in the EVOLVE study can be found here: 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
Our understanding of the biology of CLL has increased dramatically in the past 20 years. This has led to more effective treatments, and researchers continue to try to understand how to use them most effectively and which patients might benefit the most. In the era of targeted therapies, new clinical trials are seeking to re-evaluate whether early treatment might be helpful for patients at high risk of disease progression.
Please enjoy this interview with Dr. Kay and Dr. Parikh.
Take care of yourself first.
Ann Liu, PhD