SAN DIEGO -- Reducing the number of cycles of chemotherapy by a third in patients with low-risk diffuse large B-cell lymphoma (DLBCL) was just as effective as the standard treatment, while substantially reducing the number of adverse events associated with the chemotherapy, researchers said here.
The standard treatment for younger patients (ages 18-60) with low-risk DLBCL has been six cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), along with six applications of rituximab (Rituxan). For the study, the regiment was reduced to four cycles of CHOP, along with the six applications of rituximab, according to Viola Poeschel, MD, of Saarland University Medical School in Homburg/Saar in Germany, and colleagues.
The result was a maintenance of efficacy, while reducing adverse events by about one-third, "which means a significant benefit for patients," Poeschel said in a presentation at the American Society of Hematology annual meeting.
The FLYER trial was a follow up to the , which showed that the addition of rituximab to CHOP improved long-term outcomes in patients with good-prognosis DLBCL.
"Therefore, it was our aim to investigate in the FLYER trial whether we could maintain efficacy and reduce toxicity by reducing CHOP cycles," Poeschel said.
The FLYER trial was an international multi-center trial that enrolled patients being treated for DLBCL at institutions in Germany, Denmark, Norway, Italy, and Israel. All patients were considered to be low risk (stage I or II cancer).
In this trial, between December 2005 and October 2016, 592 patients (ages 18-60), with an aaIPI score of 0 and without bulky disease, were randomized to receive either six cycles of CHOP plus rituximab or four cycles of CHOP plus the six standard applications of rituximab.
Of the 588 patients available for final analysis, 295 were assigned to the six-cycle treatment group, while 293 were assigned to receive four cycles of chemotherapy.
Poeschel's group found that after a median of 66 months of observation, the 3-year progression-free survival (PFS) rate for patients receiving four cycles of chemotherapy was 96% compared to 94% for patients receiving six cycles.
The event-free survival (EFS) rate was identical (89%) in both treatment arms, while the 3-year overall survival (OS) rate was 99% in the four-cycle arm compared to 98% in the six-cycle arm.
In a multivariable analysis, the hazard ratio of the four-cycle treatment group compared to the six-cycle treatment group was 1.0 (95% CI 0.7-1.6, P=0.896) for EFS, 0.9 (95% CI 0.5-1.6, P=0.797) for PFS, and 0.8 (95% CI 0.4-1.9, P=0.671) for OS.
There was no significant difference between the two groups regarding relapse rates, with 4% of the patients in the four-cycle group relapsing compared with 5% in the six-cycle group.
Reducing the number of chemotherapy cycles significantly reduced the number of adverse events. For example, patients undergoing six cycles of chemotherapy experienced 237 cases of leukocytopenia versus 171 in the group that received four cycles. And there were just 107 documented cases of anemia in the four-cycle group versus 172 in the six-cycle group.
Results were similar regarding non-hematological adverse events, with reports of 835 adverse events (of any grade) in the four-cycle group versus 1,295 in the six-cycle group.
Overall, the number of non-hematological adverse events were reduced by about one-third in the group of patients receiving four courses of CHOP plus rituximab.
The study demonstrated that two cycles of chemotherapy can be eliminated while maintaining efficacy, Poeschel said, adding that "We think this will be the new standard treatment for this patient population."
"We're certainly always looking for ways to make treatments easier for our patients, and to reduce adverse effects," commented David Steensma, MD, of the Dana-Farber Cancer Institute in Boston.
"And certainly for this subgroup of patients, it appears that we can make their treatment shorter and have less burden with equivalent efficacy," added Steensma, who was not involved in the study. "We can't extend that to other subtypes, but that's always a laudable goal. And I think this will immediately influence clinical practice."
Disclosures
The FLYER trial was supported by Deutsche Krebshilfe.
Poeschel disclosed relevant relationships with Roche and Amgen. Co-authors disclosed multiple relevant relationships with industry.
Primary Source
American Society of Hematology
Poeschel V, et al "Excellent outcome of young patients (18-60 years) with favourable-prognosis diffuse large B-C-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" ASH 2018; Abstract 781.