R-CHOP Viable For First-Line Tx of Follicular Lymphoma?

The use of rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and oral prednisone – commonly called R-CHOP – was a good first-line treatment option for patients with newly diagnosed follicular lymphoma, according to a 10-year follow-up analysis of JCOG0203 published in Lancet Haematology.

“The present trial revealed favorable overall survival in the long-term analysis of patients with advanced-stage follicular lymphoma treated with a first-line treatment, R-CHOP,” wrote researchers led by Takashi Watanbe, MD, of JCOG Data Center of the National Cancer Center Hospital, Tokyo. “This improvement is partly attributable to the low incidence of secondary malignancies, especially fatal hematological malignancies, reduced incidence of histological transformation, no death related to first-line treatment, and low frequency of death due to infectious events during the treatment and follow-up.”

The phase 2/3 study included 300 patients with stage III or IV indolent B-cell lymphoma, including follicular lymphoma. Patients were randomly assigned to six cycles of R-CHOP every 3 weeks (R-CHOP-21) or every 2 weeks (R-CHOP-14) with no rituximab maintenance.

This long-term analysis showed no difference in 10-year progression-free survival (PFS) between patients assigned to 3 weeks compared with 2 weeks of R-CHOP (33% vs 39%; hazard ratio [HR], 0.89; 95% CI, 0.67–1.17). Among those patients with grade 1-3a follicular lymphoma, the overall 10-year PFS was 36%.

The researchers found that males were significantly associated with worse PFS and in patients aged 61 or older an increased lactate dehydrogenase was significantly associated with worse overall survival.

“The report of the long-term analysis of the PRIMA study, which had a median follow-up of 9 years and assessed patients with follicular lymphoma with high tumor burden and patients who responded to initial chemoimmunotherapy, showed that 51% of the patients who received rituximab maintenance were alive without disease progression compared with 35% of the patients who did not at 10 years,” the researchers noted in their discussion.

For both arms, the incidence of histological transformation was 3.2% at 8 years and 9.3% at 10 years. Among all patients, 8.1% had a secondary malignancies at 10 years and 2.9% had a secondary hematological malignancy at 10 years.

Overall, the number of grade 3/4 adverse events was modest, the researchers wrote, likely because of “good clinical management, including taking measures to prevent of to treat adverse events such as prophylaxis against interstitial pneumonitis caused by Pneumocystis jiroveci.”

“R-CHOP can be administered to some-but not all-previously untreated patients with advanced-stage follicular lymphoma, because, after long-term follow-up of more than 10 years we report that a third of patients survive without relapse after R-CHOP treatment without rituximab maintenance,” the researchers concluded.

In an editorial that accompanied the study, Umberto Vitolo, and Annalisa Chiappella, of Azienda Ospedaliero Universitaria Citta della Salute e della Scienze di Torino, Italy, wrote that the optimum chemotherapy regimen with anti-CD20 antibody is still unknown for follicular lymphoma, but that the data from Watanabe and colleagues is reassuring.

“Improved disease control, with the introduction of monoclonal antibodies in the induction and maintenance phases, can reduce the incidence of transformation of follicular lymphoma into aggressive lymphomas,” they wrote. “However, the incidence of secondary malignancies remains an important issue, and should be monitored with prolonged long-term follow-up.”