The Bottom Line:
Patients with unmutated IgHV had longer remissions when treated with a combination of acalabrutinib plus obinutuzumab when compared to acalabrutinib alone, but there were additional side effects.
Who Performed the Research and Where Was it Presented:
Dr. Matthew Davids from Dana-Farber Cancer Institute and colleagues presented the results at the American Society for Hematology’s (ASH) Annual Meeting in 2022.
More and more research is being done on combination therapies to manage CLL and SLL. The hope is that combining therapies with complementary mechanisms of action will produce better outcomes for patients, and potentially reduce the amount of time they need to spend on treatment. However, it is not always clear what the contribution of each drug is. For example, previous studies found that adding the anti-CD20 monoclonal antibody rituximab to the BTK inhibitor ibrutinib was no better than taking ibrutinib by itself.
In this interview, our own Dr. Brian Koffman interviewed Dr. Matthew Davids, Associate Director of the Center for Chronic Lymphocytic Leukemia at Dana-Farber Cancer Institute. They discussed the results of a new study looking at whether combining the anti-CD20 monoclonal antibody obinutuzumab with the BTK inhibitor acalabrutinib provided any additional survival benefit.
Methods and Participants:
This study analyzed combined data from two previous clinical trials that compared taking acalabrutinib plus obinutuzumab in combination vs. taking acalabrutinib alone in 376 treatment-naïve CLL patients. These patients were grouped by prognostic factors and genomic features (i.e., IgHV mutation status, deletion 17p and/or TP53 status, and ≥3 chromosomal abnormalities/complex karyotype). Acalabrutinib was given as a continuous oral therapy, and obinutuzumab was administered as an intravenous (IV) therapy for six months.
- Patients with unmutated IgHV had longer progression-free survival when given the combination of acalabrutinib + obinutuzumab vs. receiving acalabrutinib alone. They also had longer overall survival.
- There was no significant difference between the two treatments for patients with deletion 17p and/or TP53 mutations.
- There was no significant difference between the two treatments for patients with a complex karyotype (≥3 chromosomal abnormalities).
- Obinutuzumab is an IV therapy, so it does require more frequent office visits to administer the drug.
- Obinutuzumab did have some additional side effects, including an increased risk of infection, a higher rate of low white blood cell (WBC) counts, and the risk of infusion reactions.
- Patients should be aware that combination therapies are a possibility for treatment, and should discuss the potential risks and benefits with their healthcare provider.
With all the new drug combinations being tested, research like this that compares a combination therapy vs. an individual drug will be important for guiding clinical decisions. Single therapies like acalabrutinib are still very effective for treating CLL / SLL and are easier to manage. However, for patients willing to take on additional risks and more complicated drug regimens, there could be potential benefits to combination therapies. As always, it is a personal decision for patients to make in consultation with their healthcare provider.
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: Contribution of Obinutuzumab to Acalabrutinib Therapy in Patients with Treatment-Naive Chronic Lymphocytic Leukemia: Analysis of Survival Outcomes By Genomic Features
Take care of yourself first.
Ann Liu, PhD