Long-term data suggest R-CHOP can be effective as first-line treatment for patients with follicular lymphoma (FL).

In a phase 2-3 trial, investigators compared R-CHOP-21 and R-CHOP-14 in a cohort of patients with indolent lymphomas, most of whom had FL.

Ten-year survival rates were similar between the R-CHOP-21 and R-CHOP-14 groups, with progression-free survival (PFS) rates of 33% and 39%, respectively, and overall survival (OS) rates of 81% and 85%, respectively.

The investigators did note that 9% of patients in each treatment group developed secondary malignancies, and grade 3 infections were a concern as well.

Takashi Watanabe, MD, PhD, of Mie University in Japan, and his colleagues reported these results in The Lancet Haematology.

The trial (JCOG0203) included 300 patients with stage III or IV indolent B-cell lymphomas from 44 Japanese hospitals.

Most patients (n=248) had grade 1-3a FL, 17 had grade 3b FL, 6 had marginal zone lymphoma, 6 had diffuse large B-cell lymphoma, 4 had mantle cell lymphoma, 2 had small lymphocytic lymphoma, 1 had plasmacytoma, 13 had other indolent B-cell lymphomas, and 3 had other lymphomas.

The patients were randomly assigned to receive six cycles of R-CHOP 21 (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone every 3 weeks) or R-CHOP 14 (R-CHOP every 2 weeks with granulocyte-colony stimulating factor support). Neither group received rituximab maintenance.

Overall results

The median follow-up was 11.2 years (interquartile range, 10.1 to 12.7 years).

The 10-year PFS was 33% in the R-CHOP-21 group and 39% in the R-CHOP-14 group (hazard ratio=0.89). The 10-year OS was 81% and 85%, respectively (hazard ratio=0.87).

At 10 years, the incidence of secondary malignancies was 9% in both the R-CHOP-21 group (14/148) and the R-CHOP-14 group (14/151).

The most frequent solid tumor malignancies were stomach (n=5), lung (n=4), colon (n=3), bladder (n=2), and prostate (n=2) cancers. Hematologic malignancies included myelodysplastic syndromes (n=6), acute myeloid leukemia (n=2), acute lymphoblastic leukemia (n=1), and chronic myeloid leukemia (n=1).

There were nine deaths from secondary malignancies, four in the R-CHOP-21 group and five in the R-CHOP-14 group.

The rate of grade 3 adverse events was 18% (n=53) for the entire cohort. Grade 3 infections occurred in 23% of the R-CHOP-21 group and 12% of the R-CHOP-14 group.

Focus on grade 1-3a FL

Among the 248 patients with grade 1-3a FL, the PFS (for both treatment groups) was 45% at 5 years, 39% at 8 years, and 36% at 10 years. The OS was 94% at 5 years, 87% at 8 years, and 85% at 10 years.

Histological transformation was observed in 11% of the patients who had grade 1-3a FL at enrollment. The cumulative incidence of histological transformation was 2.4% at 3 years, 3.2% at 5 years, 8.5% at 8 years, and 9.3% at 10 years.

Secondary malignancies occurred in 10% (12/125) of the R-CHOP-21 group and 11% (13/123) of the R-CHOP-14 group.

The cumulative incidence of hematologic secondary malignancies at 10 years was 2.9%.

The investigators noted that the actual incidence of secondary solid tumors or hematologic malignancies apart from the setting of autologous stem cell transplants is not known. They emphasized that patients should be followed beyond 10 years to ensure the risk of secondary malignancies is not underestimated.

“Clinicians choosing a first-line treatment for patients with follicular lymphoma should be cautious of secondary malignancies caused by immunochemotherapy and severe complications of infectious diseases in the long-term follow-up—both of which could lead to death,” the investigators wrote.

This study was supported by the Ministry of Health, Labour and Welfare of Japan and the National Cancer Center Research and Development Fund of Japan.

Dr. Wantanabe has received honoraria from Bristol-Myers Squibb, Takeda, Taisho Toyama, Celgene, Nippon Shinyaku, and Novartis and funding resources from TakaraBio and United Immunity to support the Department of Immuno-Gene Therapy at Mie University. Multiple co-authors reported similar relationships.

R-CHOP effective as first-line treatment in FL