While young patients with diffuse large B-cell lymphoma (DLBCL) are typically treated with six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), results from the FLYER trial suggest that a subgroup of young patients with favorable-prognosis disease can achieve the same clinical benefit with four cycles of R-CHOP plus two cycles of rituximab monotherapy.
“With a shorter duration of chemotherapy, patients are back to daily life with their families and back to work more quickly,” said lead study author Viola Poeschel, MD, from Saarland University Medical School in Germany, who presented the findings at the 2018 ASH Annual Meeting.
The FLYER trial was based on results from an earlier study in which patients with an age-adjusted International Prognostic Index (aaIPI) score of 0 without bulky disease had high rates of three-year event-free survival (EFS) and progression-free survival (PFS) with a standard regimen of rituximab plus CHOP chemotherapy. “Our aim was to see if we could maintain efficacy and reduce toxicity in patients meeting these criteria by reducing the number of CHOP cycles,” Dr. Poeschel explained.
In this trial, the researchers randomized patients aged 18 to 60 years who had an aaIPI of 0 and non-bulky disease (<7.5 cm) to receive either six cycles of CHOP (n=295) or four cycles of R-CHOP plus two cycles of rituximab (n=293). This was a “relatively young patient population” with a median age of 48 years (range not reported), and demographics were well balanced between each group, the authors noted. Most patients had stage I or II disease and were considered to have low-risk disease.
At a median follow-up of 66 months (range not reported), the rates of three-year PFS, EFS, and overall survival (OS) were similar between each group:
- PFS: 94% with 6 cycles vs. 96% with 4 cycles (hazard ratio [HR] = 0.9; 95% CI 0.5-1.6; p=0.8)
- EFS: 89% vs. 89% (HR=1.0; 95% CI 0.7-1.6; p=0.9)
- OS: 98% vs. 99% (HR=0.8; 95% CI 0.4-1.9; p=0.67)
All patients did well with R-CHOP, the researchers noted, with a similar low frequency of relapses in each arm: 4 percent of patients in the four-cycle group and 5 percent in the six-cycle group.
The results also suggested that reducing the number of CHOP cycles from six to four also reduced the number of adverse events by approximately one-third (TABLE). Cytopenias were more frequent in the six-cycle group (80% and 60%), and overall, “we observed only two therapy-related deaths in the six-cycle arm and none in the four-cycle arm,” Dr. Poeschel said.
While these results demonstrate that four cycles of CHOP are to six cycles, Dr. Poeschel noted that the findings are not generalizable to the larger population of patients with higher-risk DBLCL or patients outside of the well-defined subgroup enrolled in this study. She added that longer-term follow-up is needed to monitor delayed toxicity.
The authors report financial relationships with Roche, Novartis, Amgen, and Bristol-Myers Squibb.
Poeschel V, Held G, Ziepert M, et al. Excellent outcome of young patients (18-60 years) with favourable-prognosis diffuse large B-cell lymphoma (DLBCL) treated with 4 cycles CHOP plus 6 applications of rituximab: results of the 592 patients of the FLYER trial of the DSHNHL/GLA. Abstract #781. Presented at the 2018 ASH Annual Meeting, December 3, 2018; San Diego, CA.