Introduction to Relapsed Follicular Lymphoma treatment

Managing relapsed follicular lymphoma treatment requires a delicate balance between therapeutic efficacy and patient safety. The HOVON110/ReBeL study recently provided primary and final analysis results comparing two potent regimens: lenalidomide-rituximab (R2) and the triplet combination with bendamustine (R2B). While the R2 regimen is a standard option for relapsed/refractory follicular lymphoma (R/R FL), prospective data on the addition of bendamustine have been limited. This randomized phase II trial evaluated investigator-assessed complete remission (CR) rates and severe toxicity as co-primary endpoints to determine the feasibility of these approaches.

Survival and Remission Outcomes

The trial enrolled 92 patients before stopping early due to slow accrual. Although the study ended prematurely, the long-term data remain highly informative. At the end of induction, investigator-assessed CR rates reached 11.4% for R2 and 15.2% for R2B. With a median follow-up of 74 months, the study highlighted significant differences in long-term survival. At 60 months, the event-free survival (EFS) was 39.5% for the R2 group compared to 56.4% for the R2B group. Furthermore, overall survival (OS) was excellent in both arms, reaching 72.1% for R2 and 86.3% for R2B. Consequently, R2B appears to offer a numerically longer survival benefit for patients with relapsed disease.

Toxicity Profiles in Relapsed Follicular Lymphoma treatment

Safety considerations are paramount when intensifying therapy with bendamustine. Severe toxicities occurred in 13.0% of patients in the R2B arm, while the R2 arm reported a lower rate of 6.8%. Additionally, grade 3-4 adverse events were more frequent with the R2B regimen, affecting 66% of patients compared to 43% in the R2 group. Despite the higher toxicity in the triplet arm, researchers noted no treatment-related deaths in the R2B group. In contrast, the R2 arm saw two pneumonia-related deaths. These findings suggest that while R2B is more effective, it demands careful monitoring due to its higher adverse event profile.

Clinical Implications for Hematologists

Both R2 and R2B represent effective strategies for managing R/R FL. However, the choice between these regimens should be individualized based on patient fitness and risk factors. While R2B leads to more durable remissions, the increased toxicity may not be suitable for all patients. Therefore, clinicians must weigh the potential for improved EFS against the risk of severe side effects. Overall, the HOVON110/ReBeL study confirms that R2-based combinations are robust options in the modern treatment landscape.

Frequently Asked Questions

Which regimen showed better survival in the HOVON110 study?

The R2B (lenalidomide-rituximab-bendamustine) regimen showed numerically longer median event-free survival (56.4% vs 39.5%) and overall survival (86.3% vs 72.1%) at 60 months compared to R2 alone.

Is R2B more toxic than R2 for relapsed follicular lymphoma treatment?

Yes, the R2B regimen was associated with higher toxicity. Severe toxicities occurred in 13% of R2B patients versus 6.8% in R2 patients, and grade 3-4 adverse events were also more common in the R2B arm.

What was the complete remission rate at the end of induction?

The complete remission rates were relatively low for both arms, with 11.4% in the R2 arm and 15.2% in the R2B arm based on CT assessments.

Disclaimer: This content is for informational and educational purposes only. It does not constitute medical advice or establish a doctor-patient relationship. Clinicians should use their professional judgment when applying this information. Refer to the latest local and national guidelines for clinical practice.

References

Kersten MJ et al. Lenalidomide-rituximab or lenalidomide-rituximab-bendamustine for relapsed/refractory follicular lymphoma: primary and final analysis of the randomized phase II HOVON110/ReBeL study. Haematologica. 2026 Apr 16. doi: 10.3324/haematol.2025.300152. PMID: 41988778.