Higher World Health Organization grades of follicular lymphoma correlate with better outcome in two Nordic Lymphoma Group trials of rituximab without chemotherapy

Abstract

A common treatment for follicular lymphoma is rituximab monotherapy. To identify patients for whom this regimen is adequate as first-line therapy, we applied the World Health Organization (WHO) classification for grading follicular lymphoma in a prospective central pathology review of the biopsies of previously untreated patients in two randomized trials of rituximab without chemotherapy. In the first trial (n₁ = 53), higher WHO grades correlated with longer time to next treatment, independently of clinical prognostic factors (p = 0.030); the finding was replicated in the second trial (n₂ = 221; p = 0.019). Higher grades were associated with better treatment responses (p = 0.018). Furthermore, also grades externally confirmed by independent local pathologists correlated with time to next treatment (p = 0.048). Flow cytometry in a separate patient series showed that the intensity of CD20 increased with the malignant cell size (p < 0.00005). In conclusion, WHO grade 1 follicular lymphoma correlates with inferior outcome after rituximab monotherapy. WHO grading might provide a clinically useful tool for personalized therapy.

Keywords::

• Follicular lymphoma
• WHO
• grades
• rituximab
• CD20

Acknowledgements

We thank all the people who participated in the Nordic Lymphoma Group trials, and Jan Delabie and Stefan Deneberg for helpful suggestions when we wrote the manuscript.

Support from the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, and from the Nordic Cancer Union, the Swedish Cancer Society and the Swedish Research Council, is acknowledged.

Potential conflict of interest:

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