Shorter R-CHOP regimen noninferior in certain DLBCL patients


©ASH/Scott Morgan 2018

Viola Poeschel, MD

SAN DIEGO—A shortened regimen of four cycles of rituximab (R) plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy was noninferior in efficacy to the standard six cycles of R-CHOP in younger patients with favorable-risk diffuse large B-cell lymphoma (DLBCL), according to investigators of the FLYER trial.

In addition, the truncated regimen was associated with about a one-third reduction in non-hematologic adverse events.

Viola Poeschel, MD, of Saarland University Medical School in Homburg/Saar, Germany, reported results of this study on behalf of the German High-Grade Non-Hodgkin’s Lymphoma Study Group/German Lymphoma Alliance at the 2018 ASH Annual Meeting (abstract 781).

Among 588 evaluable patients younger than 60 with favorable-prognosis DLBCL, there were no significant differences in progression-free survival (PFS), event-free survival (EFS), or overall survival (OS) between patients who received four cycles of R-CHOP and those who received six cycles, Dr. Poeschel reported.

“Six cycles of R-CHOP led to a higher toxicity with respect to leukocytopenia and anemia, both of any grade and also of grades 3 to 4, compared to four cycles of R-CHOP,” she said.

The findings suggest that, 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 results of the MInT trial, in which a subpopulation of favorable-prognosis DLBCL patients had a 3-year PFS rate of 89%.

The FLYER trial (NCT00278421) was designed as a non-inferiority 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 six-cycle group and 96% for the four-cycle group.

“As the lower limit of the 95% confidence interval of our experimental arm was 94%, it is shown that it is definitely non-inferior 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.

Treatment with six cycles was associated with more frequent hematologic adverse events than four cycles. Leukopenia of any grade occurred in 237 and 171 patients, respectively. Grade 3-4 leukopenia occurred in 110 and 80 patients, respectively.

Any-grade anemia occurred in 172 patients assigned to six cycles and 107 assigned to four cycles. Rates of grade 3-4 anemia were similar between the groups, as were rates of thrombocytopenia of any grade or grade 3-4.

Non-hematologic adverse events of any grade or grade 3-4 that were more frequent with six cycles included parasthesia, nausea, infection, vomiting, and mucositis.

The total number of non-hematologic 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,” said David Steensma, MD, of the Dana-Farber Cancer Institute/Harvard Cancer Center in Boston, Massachusetts.

Drs. Steensma and Poeschel both cautioned that the results of this 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 supported by Deutsche Krebshilfe. Dr. Poeschel disclosed travel grants from Roche and Amgen. Dr. Steensma had no disclosures relevant to the study.

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