Examining MRD-Driven Consolidation with Rituximab in Early Stage Follicular Lymphoma

The use of rituximab as a consolidation strategy effectively improved progression-free survival in patients with follicular lymphoma who were minimal residual disease (MRD)-positive after undergoing involved field radiation therapy (IF-RT), according to the results of a study published in British Journal of Haematology.

Patients who were MRD-positive after IF-RT received rituximab 375 mg/m². Progression-free survival was significantly longer among these patients compared with untreated MRD-positive patients (P=.049).

“Our goal is to use MRD evaluation to better identify the proportion of patients not destined to be cured by radiation therapy (RT),” wrote Alessandro Pulsoni, of Sapienza University, and colleagues. “The addition of rituximab to this subgroup potentially resistant to RT could theoretically increase the proportion of cured patients.”

In the study, Pulsoni and colleagues looked at 67 consecutive patients with stage I/II follicular lymphoma and tested for presence of BCL2/IGH rearrangement using polymerase chain reaction (PCR), real time quantitative-PCR (RQ-PCR), and digital droplet PCR (ddPCR). Seventy-two percent of patients were BCL2/IGH positive at diagnosis.

All patients were treated with IF-RT, and after 2005, patients with MRD-positive disease after radiation also received rituximab. The median follow-up was 82 months.

Median progression-free survival was significantly better in patients with undetectable/low levels of circulating BCL2/IGH positive cells at diagnosis and in those who were MRD negative during follow-up (P=.0038).

After undergoing IF-RT, half of patients became MRD-negative. Of those who did not, 84% achieved negative status after undergoing rituximab treatment.

“With regard to the treatment strategy for early stage follicular lymphoma, the validity of the standard approach by IF-RT has been questioned by some authors who reported similar survival results independently of the treatment strategy employed in early stage follicular lymphoma,” the researchers wrote. “An alternative approach with rituximab alone could be thus considered in selected cases to spare radiotherapy. However, the potential role of IF-RT as a curative solution in localized follicular lymphoma has to be kept in mind, whilst no data are available in the literature on a definitive curative role of rituximab.”

Commenting on the results, Jonathan W. Friedberg, MD, MMSc, director of the Wilmot Cancer Institute at the University of Rochester Medical Center in Rochester, New York, said that in patients with early stage follicular lymphoma, standard treatment often includes involved site radiation therapy.

“The current study also included patients with stage II disease, which may explain the relatively high rate of detectable MRD after radiation therapy,” Friedberg said. “Patients with stage II disease have inferior outcomes with radiation therapy alone.”

However, because the study was not randomized, he said it is not possible to determine the true effect of rituximab in the setting of MRD detectable disease after radiation therapy.

“The demonstration of improved progression-free survival is provocative, and worthy of investigation in prospective, randomized trials,” Friedberg said. “Additionally, the methods of MRD detection are evolving, and whether PCR is the best strategy for precision medicine approach is not known and should be compared with more sensitive techniques.”