Rituximab-based chemotherapy can significantly reduce the risk of transformation of follicular lymphoma (FL) from an indolent to an aggressive histology, such as diffuse large B-cell lymphoma, results of a retrospective pooled analysis have suggested.

For 509 patients with FL who experienced histologic transformation, the 10-year cumulative hazard of histologic transformation was 5.2% for patients who had received rituximab and 8.7% for those who had not. The hazard ratio for transformation was greater for those patients who received rituximab during only the induction phase than it was for those patients who received the drug during both induction and maintenance, reported Massimo Federico, MD, of the University of Modena and Reggio Emilia in Modena, Italy, and his colleagues in the Aristotle Consortium.

“Despite the intrinsic limitations related to the retrospective nature of our study, we confirmed that the cumulative hazard of histological transformation as a first event in follicular lymphoma can be reduced significantly by introducing rituximab to a backbone therapy. Moreover, our data also confirm that histological transformation still has an adverse effect on patient outcome, although it is less catastrophic than the pre-rituximab regimens,” they wrote in the Lancet Haematology.

These investigators, from 11 cooperative groups or institutions across Europe, pooled data on patients aged 18 years and older who had a histologically confirmed diagnosis of grade 1, 2, or 3a FL between Jan. 2, 1997, and Dec. 20, 2013.

They defined histologic transformation as a biopsy-proven aggressive lymphoma that occurred as a first event after first-line therapy.

Data on a total of 8,116 patients were available for analysis; 509 of these patients had had histologic transformations. After a median follow-up of 87 months, the 10-year cumulative hazard for all patients was 7.7%. The 10-year cumulative hazard – one of two primary endpoints – was 5.2% for patients who had received any rituximab versus 8.7% for those who did not, which translated into a hazard ratio of 0.73 (P = .004).

Among patients who received rituximab during induction only, the 10-year cumulative hazard was 5.9%, and it was 3.6% among those who received rituximab during induction and maintenance phases of treatment. This difference translated into a HR of 0.55 (P = .003).

The benefit of rituximab induction and maintenance – compared with induction only – held up in a multivariate analysis controlling for age at diagnosis, sex, FLIPI (Follicular Lymphoma International Prognostic Index) score, active surveillance vs. treatment, and FL grade (HR, 0.55; P = .016).

There were 287 deaths among the 509 patients with transformation, resulting in a 10-year survival after transformation of 32%.

The 5-year survival after transformation was 38% for patients who were not exposed to rituximab, 42% for patients who received induction rituximab, and 43% for those who received both induction and maintenance rituximab, but the differences between the three groups were not statistically significant.

“More comprehensive knowledge of the biological risk factors for follicular lymphoma transformation and the molecular pathways involved is likely to help clinicians make more accurate prognostic assessments and also inform the potential usefulness of novel drugs for the treatment of follicular lymphoma,” the researchers wrote.

The study was funded by the European Lymphoma Institute and other research groups. The researchers reported having no financial disclosures.

SOURCE: Federico M et al. Lancet Haematol. 2018 Jul 4. doi: 10.1016/S2352-3026(18)30090-5.

Rituximab reduces risk of follicular lymphoma transformation