Dr. Jason Westin, representing MD Anderson Cancer Center at the 2023 American Society of Hematology (ASH) conference, shared with HealthTree about an innovative clinical trial that could revolutionize treatment for patients with DLBCL.

What is R-CHOP

Traditionally, the frontline therapy for aggressive lymphomas like DLBCL has been a combination of drugs known as R-CHOP. This combination contains the chemotherapy drugs cyclophosphamide, doxorubicin hydrochloride, and vincristine sulfate, the targeted therapy drug rituximab, and the steroid hormone prednisone. Unfortunately, one-third of patients with DLBCL do not achieve durable remission and develop more disease during or after R-CHOP therapy. Dr. Westin and his team at MD Anderson are challenging this longstanding approach with a clinical trial that explores the use of novel targeted therapies right from the point of diagnosis.

Combined Lenalidomide, Tafasitamab, Rituximab, and Acalabrutinib (LTRA) Treatment for DLBCL

In this groundbreaking trial, patients newly diagnosed with DLBCL were administered a combination of modern targeted therapies for their initial four cycles. These combined therapies were lenalidomide, tafasitamab, rituximab, and acalabrutinib (LTRA). Patients received lenalidomide by mouth on days 1-10, tafasitamab through IV on days 1, 8, and 15, rituximab through IV on day 1, and acalabrutinib by mouth twice daily throughout the 21 day cycle. All patients received LTRA for four cycles, followed by a PET/CT scan.

The goal of the study was to assess if these targeted therapies, distinct from the conventional chemotherapies dating back to the 1970s, could yield a better response. If patients achieved a complete response, meaning their PET scan was clear before any chemotherapy, they received 2 cycles of R-CHOP after finishing the LTRA combination. If they had less than a complete response, they received 6 cycles or R-CHOP.

Smart Stop Trial Results

The primary objectives for the first group of patients were to determine: 

• The overall response rate (ORR) after four cycles of the initial treatment
• The complete response rate (CRR) at the end of all the treatment cycles

In the first group of 30 patients (cohort 1), everyone responded well to the treatment. After 4 cycles, all patients showed a positive response (100%), and a good number had a complete response (64%). After a bit more treatment, the complete response rate increased to 95%, and by the end of all therapy, it reached 100%. To date, no patient has had their lymphoma progress, including the first 6 patients who had 3 and 6 month follow up scans. These findings challenge the long-standing norm of administering six cycles of R-CHOP (chemotherapy).

While Dr. Westin notes that this information isn't ready to alter standard practices immediately, it emphasizes the transformative power of clinical trials. Exploring and integrating tomorrow's therapies today represents a crucial advantage of participating in such trials.