ASH 2023: On the Way to Improved Treatment for Newly Diagnosed Follicular Lymphoma with Acalabrutinib Added to Lenalidomide and Rituximab 

During the recent ASH 2023 conference, Paolo Strati, physician and assistant professor from MD Anderson Cancer Center in Houston, Texas, shared updates from his study looking at the treatment combination of acalabrutinib, lenolidamide and rituximab in previously untreated patients with follicular lymphoma who had advanced stage disease. 

Watch Dr. Strati's Interview Here

Study Rationale

Follicular lymphoma is the most common slow-growing B-cell lymphoma in the United States and Europe, and newly diagnosed patients are currently treated with chemotherapy based regimens. There has been a lot of interest in trying to develop chemotherapy-free treatment options for follicular lymphoma particularly because patients with this type of lymphoma tend to be older, making chemotherapy more difficult to tolerate. 

Currently, in the relapsed/refractory setting, patients with follicular lymphoma can be treated with a chemotherapy-free combination of lenalidomide and rituximab, also known as R², but this combination is not formally approved the by Food and Drug Administration (FDA) as first-line treatment for follicular lymphoma because research has not shown it to be more effective than chemotherapy.

A Little More About R²:

• Lenalidomide (also known as Revlimid): This is an immunomodulatory drug, meaning that it can change certain parts of the immune system such as inflammatory compound production, T-cell activation and NK cell function. This medication is a pill. 
• Rituximab (also known as Rituxan): This is a monoclonal antibody that binds to CD20-positive cells and induces cell death. This medication is an IV infusion.
• This combination of drugs is currently approved for those with relapsed or refractory follicular lymphoma. 

Dr. Strati’s trial adds acalabrutinib to R². Acalabrutinib is a BTK inhibitor that targets B-cell receptors and is a pill currently approved for the FDA for several types of B-cell lymphoma but not for follicular lymphoma. Dr. Strati hypothesized that the addition of acalabrutinib to R² may make the therapy stronger by targeting a very specific type of immune cell called monocytes or macrophages. 

Trial Details and Findings 

This was a Phase II trial that enrolled 24 patients with previously untreated, advanced staged follicular lymphoma. These patients specifically had grade 1 to 3A, stage 3-4 disease. The median age was 62 years with ages that ranged from 40 to 82. The medications were administered over 13 cycles. Acalabrutinib was given 100 mg by mouth twice a day in a 28-day cycle for 13 cycles, lenalidomide was given 20 mg by mouth daily on days 1-21, starting from cycle 2, and rituximab was administered 375 mg/m2 via IV weekly during cycle 2, and on day 1 of future cycles.

Overall the combination was very safe and did not seem to create any additional side effects when compared to R² alone or acalabrutinib alone. Most importantly, this triplet combination appeared to be very effective. Typically with R², only 50% of patients achieve a complete response (CR). In this trial, overall 92% of patients were able to achieve a CR. Most patients achieved a complete response within 3 months. After 29 months of follow-up, 25% of patients experienced disease progression, including two cases of transformation at 5 and 7 months. The two-year progression-free survival (PFS) rate was 79.2%, indicating good control of the disease.

Peripheral blood was also collected from participants, and the researchers observed that acalabrutinib was able to change the monocytes and macrophages in these patients to make them better at attacking the lymphoma alongside R².

What's Next?

Dr. Strati is very excited about these results and based on the success of this phase II trial, it has been amended to allow 26 more patients to join the trial. In this amended trial, the number of treatment cycles has also been reduced from 13 to 6. If this amended trial continues to show positive results, the next step will be a randomized trial comparing this new immunotherapy combination to chemotherapy with the hopes that Dr. Strati and his team will be able to bring the proposal to the FDA to make immunotherapy a front line treatment option for newly diagnosed follicular lymphoma. 

To learn more about Dr. Strati's open trial and to see if you qualify to participate, view the trial listing here.