Consolidative High-Dose Therapy, Autologous Stem Cell Transplant After R-CHOP for Follicular Lymphoma Does Not Improve Survival

Consolidative high-dose therapy and autologous stem cell transplantation (HDT/ASCT) should not be offered to patients with follicular lymphoma who are in their first remission after having initially received treatment with Rituxan (rituximab) plus the chemotherapies cyclophosphamide, doxorubicin and vincristine in addition to the steroid prednisone (R-CHOP), according to the authors of a recent study published in Blood Advances.

“Even with modern immunochemotherapies, approximately 20% of patients (with follicular lymphoma) experience early progression of disease,” the authors wrote. “Retrospective studies have demonstrated prolonged survival in patients with (progression of disease within 24 months) who received high-dose therapy followed by autologous stem cell transplantation.”

As a result of that data current United States and European guidelines recommend HDT/ASCT for those whose disease progressed within 24 months, are medically fit and who have achieved a second remission.

“Current guidelines do not recommend consolidative HDT/ASCT for patients with advanced (follicular lymphoma) in first remission after state-of-the-art immunochemotherapy,” the authors wrote. “So far, however, remarkably few data were available to support this recommendation in the era of modern immunochemotherapy, in particular with respect to high-risk cohorts.”

And although consolidative HDT/ASCT is not a recommended treatment option for patients with follicular lymphoma who are in their first remission following treatment with immunochemotherapy, the authors wanted to see if they could determine if previously untreated patients with high-risk disease could benefit from dose-intensified frontline regimens.

The authors reviewed the outcomes of 431 patients with advanced follicular lymphoma who were medically fit and 60 years old or younger from the German Low-Grade Lymphoma Study Group 2000 trial. This patient population received immunochemotherapy with R-CHOP as an induction treatment and were randomized to HDT/ASCT – which consisted of total body irradiation, high-dose cyclophosphamide and reinfusion of peripheral blood stem cells.

The authors performed intention-to-treat and actual treatment survival and regression analyses to asses HDT/ASCT’s impact on treatment outcomes in patients. Following induction therapy with R-CHOP, patients were randomized to receive either consolidative HDT/ASCT (216 patients) or interferon maintenance (215 patients).

Data from the intention-to-treat analysis showed that 10-year failure-free survival (FFS) (the absence of relapse, non-relapse mortality or addition of another systemic therapy) was 62% in the HDT/ASCT group compared to 56% in the other group. Patients in the non-HDT/ASCT group (85%) had a higher 10-year overall survival rate compared to patients in the HDT/ASCT group (80%).

The benefit of HDT/ASCT for FFS reached statistical significance in the patients who were stratified by actual treatment analysis.

The authors wanted to assess outcomes in a subset of patients since they did not observe a survival difference in the overall patient population. Of 400 evaluable patients, 27% were classified as high risk according to the FL International Prognostic Index (FLIPI). The results demonstrated that patients with FLIPI of low- to-intermediate risk had a trend toward longer FFS when receiving HDT/ASCT, there was no difference in those with high-risk cases. There was also no significant difference regarding overall survival in patients who received HDT/ASCT.

“Collectively, our mature data provide the most definitive evidence supporting current guidelines, that HDT/ASCT should not be offered to unselected patient cohorts in the frontline setting,” the authors wrote. “In contrast, HDT/ASCT is an effective salvage treatment of early relapsed (follicular lymphoma) after initial immunochemotherapy and recommended for patients with chemosensitive disease who are considered eligible for dose-intensified approaches by most current treatment guidelines.”