SAN DIEGO – A shortened regimen of four cycles of rituximab plus CHOP chemotherapy was noninferior in efficacy to the standard six cycles of R-CHOP in patients aged under age 60 years with favorable-risk diffuse large B-cell lymphoma (DLBCL), and the truncated regimen was associated with about a one-third reduction in nonhematologic adverse events, investigators in thereported.
Among 588 evaluable patients aged younger than 60 years with favorable-prognosis diffuse DLBCL, there were no significant differences in either progression-free survival (PFS), event-free survival, or overall survival (OS) between patients who were randomly assigned to therapy with four cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), compared with patients assigned to six cycles, reported Viola Poeschel, MD, of Saarland University in Homburg, Germany.
“Six cycles of R-CHOP led to a higher toxicity with respect to leukocytopenia and anemia, both of any grades and also of grades 3 to 4, compared to four cycles of R-CHOP,” she said in a briefing at the annual meeting of the American Society of Hematology.
For younger patients with favorable-prognosis DLBCL – defined as an age-adjusted International Prognostic Index score of 0 and low tumor burden (less than 7.5 cm) – four cycles of R-CHOP can be a new standard of care, Dr. Poeschel said.
The investigators were prompted to look at the question of a shorter R-CHOP regimen by the results of the MInT trial, in which a subpopulation of favorable-prognosis DLBCL had a 3-year PFS rate of 89% (). The FLYER trial was designed as a noninferiority study to see whether in a similar group of patients reducing the number of R-CHOP cycles could maintain efficacy while reducing toxicity.
At a median follow-up of 66 months, the PFS rate, the primary endpoint, was 94% in the R-CHOP 6 group, compared with 96% for R-CHOP 4.
“As the lower limit of the 95% confidence interval of our experimental arm was 94%, it is shown that it is definitely noninferior to the standard arm, six cycles of R-CHOP,” Dr. Poeschel said.
Similarly, the rate of 3-year OS was 98% in the six-cycle group, compared with 99% in the four-cycle group, and the survival curves were virtually superimposable out to more than 10 years of follow-up.
R-CHOP 6 was associated with more frequent hematologic adverse events, compared with R-CHOP 4, with leukopenia of any grade occurring in 237 versus 171 patients, respectively, and grade 3 or 4 events occurring in 110 versus 80 patients, respectively.
Any grade anemia occurred in 172 patients assigned to six cycles versus 107 assigned to four cycles. Rates of grade 3-4 anemia and thrombocytopenia of any grade or of grade 3-4 were similar between the groups.
Nonhematologic adverse events of any grade or of grade 3 or 4 that were more frequent with R-CHOP 6 versus R-CHOP 4 included all events considered together, paresthesias, nausea, infection, vomiting, and mucositis.
As noted before, the total number of nonhematologic adverse events was reduced by about one-third.
“We are certainly always looking for ways to make treatments easier for our patients to reduce adverse effects, and certainly for this subgroup of patients it appears that we can make their treatment shorter and have less burden but equivalent efficacy,” commented, from the Dana-Farber Cancer Institute/Harvard Cancer Center in Boston, who moderated the briefing.
Dr. Steensma and Dr. Poeschel both cautioned that the results of the study pertain only to those patients with DLBCL who are younger and have favorable-prognosis disease.
“We can’t extend it to other subtypes of large cell lymphoma, but that’s always a laudable goal, so I think this will immediately influence clinical practice,” Dr. Steensma said.
The study was sponsored by the German High-Grade Non-Hodgkin’s Lymphoma Study Group. Dr. Poeschel reporteed travel grants from Roche and Amgen. Dr. Steensma reported no disclosures relevant to the study.
SOURCE: Poeschel V et al. ASH 2018, Abstract 781.