Toxicity Reduced With Fewer Lines of CHOP Plus Rituximab in DLBCL

According to findings from the FLYER trial presented at the 2018 ASH Annual Meeting, treatment with 2 fewer frontline cycles of R-CHOP greatly reduced toxicity in younger patients with low-risk diffuse large B-cell lymphoma (DLBCL). The progression-free survival (PFS) rates were also similar between the 2 arms.¹

The 3-year PFS rate at a median follow-up of 66 months was 94% (95% CI, 91-97) for patients who received 6 cycles of frontline R-CHOP (n = 295) versus 96% (95% CI, 94-99) in those who received 4 cycles of frontline R-CHOP followed by 2 cycles of rituximab (n = 293). At a median follow-up of 67 months, the overall survival (OS) rates were 98% (95% CI, 96-99) versus 99% (95% CI, 98-100), respectively.

The 6-cycle R-CHOP arm experienced a higher total of nonhematologic grade 3/4 adverse events (AEs) compared to the 4-cycle arm, at 70 versus 46. With hematologic AEs, the number of patients with grade 3/4 leukopenia (110 vs 80), anemia (8 vs 2), and thrombocytopenia (7 vs 5) was higher in the group receiving 6 R-CHOP cycles.

“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, of Saarland University Medical School in Homburg/Saar, Germany. “Our study shows you can spare 2 cycles of chemotherapy and it is equally effective. We think this will be the new standard treatment for this patient population.”

The 6-cycle upfront standard for young, low-risk patients with DLBCL was established by the MInt trial. In the study, patients with an age-adjusted international prognostic index (aaIPI) score of 0 and no bulky disease who received 6 upfront cycles had 3-year event-free survival, PFS, and OS rates of 89%, 95%, and 98%, respectively.²

The FLYER trial randomized a total of 592 patients aged 18 to 60 years (median, 48 years). Of those patients, 588 were evaluable for the efficacy analysis. Patients were enrolled at sites in Germany, Denmark, Norway, Italy, and Israel.

Ninety-nine percent of patients had disease with an aaIPI of 0, 1% had disease with an aaIPI of 1, and 0.3% had bulky disease (diameter ≥7.5 cm). According to the researchers, there were no relevant differences in patient demographics.

Patients in both arms received frontline R-CHOP on days 1, 22, 43, and 64. Patients in the longer duration arm received 2 additional cycles of R-CHOP on days 85 and 106. Those in the shorter duration arm received rituximab on days 85 and 106.

The total number of AEs among patients receiving 6 cycles of R-CHOP was 1295, compared with 835 in the group receiving 4 cycles. “AEs with 4 cycles were reduced by about a third,” said Poeschel, “This is an important and meaningful benefit to patients,” she added.

Grade 3/4 paresthesia (14 vs 12), nausea (12 vs 6), infection (23 vs 20), vomiting (7 vs 1), and mucositis (3 vs 1), all occurred in more patients in the 6-cycle arm.

The next steps for the researchers involve monitoring the health of patients from the trial for another 5 years to examine whether reducing the number of R-CHOP cycles will also lower the long-term toxicities of chemotherapy.

David Steensma, MD, of Dana-Farber Cancer Institute and Harvard Medical School, who moderated the ASH press briefing at which the results were presented, commented on the FLYER findings.

“We are always looking for ways to make treatments easier for our patients—to reduce adverse events. And certainly, for this defined subgroup of patients, it appears that we can make their treatment shorter with less burden, but with [comparable] efficacy…I think this will immediately influence clinical practice.

References:

1. 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. Presented at: ASH Annual Meeting and Exposition; December 4-8, 2018; San Diego, California. Abstract 781.
2. Pfreundschuh M, Trümper L, Osterborg A, et al. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006;7(5):379-391.