This question lies at the heart of modern lymphoma care, where the choice between two effective regimens—R-CHOP and R-bendamustine—becomes especially challenging for patients with high SUV measurements on baseline PET scans.
Understanding the Players: FL, SUV, and Treatment Options
FL Prevalence
Follicular lymphoma represents nearly 30% of all non-Hodgkin lymphomas, making it one of the most common lymphoid malignancies worldwide 1 .
Disease Course
This cancer typically follows an indolent course, with an estimated overall survival of over 10 years, yet it remains incurable and characterized by multiple relapses over time 1 .
The treatment landscape transformed with the introduction of monoclonal antibodies like rituximab, which, when combined with chemotherapy, significantly improved outcomes. The two dominant first-line regimens today are:
R-CHOP
Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone
R-Bendamustine
Rituximab plus bendamustine
The complicating factor emerges from PET scan imaging, the gold standard for staging and assessing treatment response in follicular lymphoma. The Standardized Uptake Value (SUV) quantitatively measures metabolic activity within tumors, with higher values potentially indicating more aggressive disease behavior 4 .
This has led to an ongoing debate: should patients with high SUV values receive more intensive anthracycline-based treatment (R-CHOP), or does R-bendamustine offer equivalent or superior benefits regardless of SUV levels?
The GELTAMO Study: A Closer Look at Real-World Evidence
A recent multicenter retrospective study by the Spanish GELTAMO group provides substantial insight into this question. This investigation compared 476 follicular lymphoma patients from 17 centers who received either R-CHOP or R-bendamustine followed by rituximab maintenance therapy 1 3 .
Methodology and Patient Characteristics
Patient Selection
The researchers retrospectively assessed patients with grade 1-3a follicular lymphoma with high tumor burden who were treated between January 2013 and January 2022 1 .
Treatment Protocol
All participants received full doses of their assigned treatment followed by two years of rituximab maintenance—an important consistency factor that strengthens the comparison.
Exclusion Criteria
To minimize selection bias, the investigators excluded patients who didn't complete the intended treatment protocol for reasons unrelated to toxicity, disease progression, or death 1 .
Final Analysis
The final analysis included 405 patients—245 treated with R-CHOP and 160 with R-bendamustine 1 . The groups displayed some notable differences at baseline: the R-CHOP group was generally younger and included more patients with grade 3a disease 1 .
Key Findings and Results Analysis
The GELTAMO investigation yielded several important findings:
| Response Metric |
R-Bendamustine |
R-CHOP |
Statistical Significance |
| Complete Response Rate |
Higher |
Lower |
Significant |
| Relapse Frequency |
Lower |
Higher |
Significant |
| 6-Year PFS |
79% |
67% |
p = 0.046 |
| 6-Year OS |
91% |
91% |
Not Significant |
Table 1: Treatment Response Comparison
After a median follow-up of 81 months, the 6-year progression-free survival was significantly better with R-bendamustine (79%) compared to R-CHOP (67%) 1 3 . This represents a meaningful 12% absolute difference in patients remaining progression-free.
Perhaps equally important was the toxicity profile during treatment:
| Toxicity Type |
R-Bendamustine |
R-CHOP |
Treatment Phase |
| Cytopenias |
Less Frequent |
More Frequent |
Induction |
| Neutropenia |
More Frequent |
Less Frequent |
Maintenance |
| Infectious Toxicity |
More Frequent |
Less Frequent |
Maintenance |
| G-CSF Use |
Less Frequent |
More Frequent |
Induction |
Table 2: Treatment Toxicity Profile
Induction Phase Toxicity
Cytopenias
R-CHOP: 78%
R-Benda: 42%
Maintenance Phase Toxicity
Infectious Toxicity
R-CHOP: 15%
R-Benda: 32%
During the induction phase, cytopenias (low blood counts) were significantly more common with R-CHOP, leading to more frequent use of colony-stimulating factors 1 . However, during the maintenance phase, this pattern reversed—patients who received R-bendamustine experienced more neutropenia and infectious complications 1 3 .
Despite these differences in side effects, the overall survival was identical between both groups at 91% after six years 1 3 . This paradox highlights the complex risk-benefit calculations inherent in follicular lymphoma treatment.
The SUV Question: Does Metabolic Activity Predict Treatment Response?
The central question surrounding high-SUV follicular lymphoma received direct attention in a recent analysis presented at ASH 2024 4 . This multi-center investigation drew from prospective cohorts (LEO and MER), clinical trials (FOLL12 and RELEVANCE), and a retrospective cohort of 13 Australian centers.
The researchers asked whether patients with high SUV measurements on baseline PET scans would benefit more from R-CHOP, theoretically better suited for aggressive disease, or whether R-bendamustine would prove equally effective regardless of SUV levels 4 .
Would they benefit more from intensive R-CHOP?
SUV levels did not predict treatment response to either regimen 4 .
The findings surprised many: SUV levels did not predict treatment response to either regimen 4 . When patients were divided into tertiles based on SUV measurements, R-CHOP showed inferior event-free survival in the lowest and middle tertiles compared to R-bendamustine, but no differences emerged in the highest tertile 4 .
This counterintuitive result suggests that our current understanding of SUV as a decision-making tool for treatment selection in follicular lymphoma may be incomplete. The study authors concluded that "SUV overall does not impact survival based on R-CHOP or BR treatment" 4 .
The Maintenance Debate: To Continue or Not?
Another layer of complexity involves the role of rituximab maintenance therapy following initial treatment. The GELTAMO study incorporated two years of maintenance therapy for all patients, but real-world practice varies 1 6 .
After R-CHOP
Strong evidence supports rituximab maintenance after R-CHOP, demonstrating improved progression-free survival 1 6 .
After R-Bendamustine
The benefit after R-bendamustine remains less certain. Some studies suggest that patients achieving complete remission with R-bendamustine may not need maintenance therapy, while those with partial responses might benefit 6 .
This decision carries practical implications, as the GELTAMO study noted increased neutropenia and infectious toxicity during maintenance for patients initially treated with R-bendamustine 1 . This aligns with findings from the GALLIUM trial, which reported increased cytopenias and infections when maintenance was administered after bendamustine-based induction 6 .
Conclusion: Navigating the Complex Treatment Landscape
The question of optimal first-line treatment for follicular lymphoma patients with high SUV measurements remains nuanced. Current evidence suggests that R-bendamustine provides better progression-free survival regardless of SUV levels, while overall survival remains equivalent between the two approaches 1 3 4 .
Key Clinical Takeaways
R-bendamustine offers better PFS
OS is equivalent between regimens
Toxicity profiles differ by phase
The toxicity profiles differ meaningfully—R-CHOP causes more blood count issues during induction, while R-bendamustine leads to more complications during maintenance 1 . These patterns, combined with individual patient factors like age and comorbidities, must inform treatment decisions.
As research continues to refine our understanding, the emerging picture is one of personalized medicine—matching treatment intensity to disease characteristics and patient preferences. The SUV measurement, while providing valuable prognostic information, does not appear to reliably predict which treatment will yield superior outcomes, reminding us that in follicular lymphoma management, simple answers often remain elusive.
The future of follicular lymphoma treatment will likely involve more sophisticated biomarkers and risk stratification tools, moving beyond SUV measurements alone to create truly personalized treatment approaches.