Comparing Chemotherapy Cycles Using Positron Emission Tomography-Adapted Therapy Among Patients With Non-Bulky, Low-Risk DLBCL

Results from an Open-Label, Randomized, Phase 3, Non-Inferiority Trial

A 4-cycle regimen of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) demonstrated comparable efficacy to the standard regimen, and yielded fewer adverse events in diffuse large B-cell lymphoma (DLBCL) patients with low-risk, non-bulky disease with interim positron emission tomography with computed tomography (PET-CT) confirmed complete response (CR), according to findings from a phase 3 trial published in Cancer Communications.  

Prior research has shown that treatment with 4 cycles of R-CHOP plus 2 cycles of rituximab is non-inferior to 6 cycles of R-CHOP among young patients with DLBCL. However, Qing Shi, Shanghai Jiao Tong University School of Medicine, Shanghai, China, and coauthors noted that whether this treatment remains efficacious among “non-bulky DLBCL patients with an [International Prognostic Index] (IPI) of 1 remains unclear.” 
 
A total of 287 patients with newly diagnosed low-risk DLBCL (IPI 0 to 1) achieving PET-CT-confirmed complete response after 4 cycles of R-CHOP were included in the intention-to-treat population. The patients were randomized to receive either 4 cycles of rituximab (4R-CHOP + 4R) or 2 additional cycles of R-CHOP plus 2 cycles of rituximab (6R-CHOP + 2R). The primary end point was 2-year progression-free survival (PFS), and secondary end points included the complete response rate and safety.

At a median follow-up of 47.3 months, the 2-year PFS rate was 95% (95% confidence interval [CI], 92% to 99%) for the 4R-CHOP + 4R group and 94% (95% CI, 91% to 98%) for the 6R-CHOP + 2R group. The absolute difference between groups was 1%, which attests to the non-inferiority of 4R-CHOP + 4R.  

As for safety, in the last 4 cycles of rituximab alone in the 4R-CHOP + 4R group, grade 3 to 4 neutropenia was significantly lower, at 16.7% compared to 76.9% in the 6R-CHOP + 2R. Additionally, there was a decreased risk of febrile neutropenia (0.0% versus 8.4%) and infection (2.1% versus 14.0%) in the 4R-CHOP + 4R group compared to the 6R-CHOP + 2R group. 

Dr Shi et al concluded, “Reducing the standard 6 cycles to 4 cycles of chemotherapy had comparable clinical efficacy and fewer adverse events in low-risk, non-bulky DLBCL with interim [positron emission tomography with computed tomography] confirmed [complete response].”

“This interim PET-adapted strategy ensures durable remission in low-risk DLBCL and identifies patients with positive interim PET who may bear potential high-risk biological features as candidates for novel mechanism-based targeted approaches or future clinical trials,” they added. 

Limitations included that this prospective trial was conducted in a single center. A large-scale randomized multicenter clinical trial is currently ongoing to provide more evidence of the efficacy and safety of 4 cycles of R-CHOP in low-risk DLBCL patients, the study authors noted. 

Source: 

Shi Q, He Y, Yi H-M, et al. Positron emission tomography-adapted therapy in low-risk diffuse large B-cell lymphoma: results of a randomized, phase III, non-inferiority trial. Cancer Commun. 2023; 43: 896–908. doi: 10.1002/cac2.12462