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Four cycles of R-CHOP is as effective as six cycles in young patients with favorable-risk diffuse large B-cell lymphoma

Results of a German phase III trial suggest that the standard treatment course for younger patients with low-risk diffuse large B-cell lymphoma (DLBCL), consisting of 6 cycles of R-CHOP, can safely be reduced by two chemotherapy cycles. In fact, the rates of progression-free survival (PFS) and overall survival (OS) at three years were almost identical with 4 and 6 cycles of chemotherapy. As such, these data indicate that chemotherapy can be reduced by a third in this disease setting, without compromising the prognosis of patients.

Based on the results of the phase III MInT trial, 6 cycles of CHOP chemotherapy plus rituximab (6x R-CHOP) has become the standard of care for younger DLBCL patients. Also in this trial, researchers were able to identify a subgroup of patients with a particularly favorable prognosis. These patients, characterized by an age-adjusted International Prognostic Index (aaIPI) of 0 without the presence of bulky disease, were found to have a 3-year event-free survival (EFS) rate of 89% with a 3-year PFS and OS rate of 95% and 98%, respectively. The objective of the presented study (FLYER) was to assess whether reducing the R-CHOP regimen with 2 cycles would be as effective as the standard regimen with reduced toxicity in this good prognosis group of DLBCL patients.

In the study at hand, 600 DLBCL patients, aged 18-60 years with an aaIPI score of 0 and no bulky disease (i.e. <7.5 cm) were randomly assigned to receive four or six cycles of CHOP. All patients received the standard six cycles of rituximab.

Patients did well with both treatment regimens, and there were no statistically significant differences between the two groups in terms of OS, relapse, or disease progression. Three years after receiving treatment, 99% of patients receiving four cycles of chemotherapy and 98% of those receiving six cycles were alive. The 3-year PFS rate of the patients receiving 4x R-CHOP + 2x R was 96% as compared to 94% in the group of patients receiving 6x R-CHOP (p=0.760). With respect to relapse rate, there was also no significant difference between the two treatment arms: 4% of the patients in the 4x R-CHOP + 2x R arm relapsed vs. 5% of the patients in the 6x R-CHOP arm.

Reducing the number of chemotherapy cycles also reduced the number of adverse events by one-third. Altogether, 1,295 adverse events occurred in the 295 patients who underwent six cycles of chemotherapy compared with 835 adverse events in the 293 patients who received just four cycles of chemotherapy. Study participants will be followed up for an additional five years to determine whether decreasing the number of chemotherapy cycles may help reduce long-term side effects of chemotherapy.

In summary, these data show that young DLBCL patients with favorable characteristics can be spared from two cycles of chemotherapy without compromising outcomes. In addition, the regimen containing 4 cycles of chemotherapy also led to fewer side effects than the standard 6 cycles of chemotherapy. As such, this de-escalated regimen will likely become the new standard treatment for this patient population.



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 2018; Abstract 781.

Speaker Viola Poeschel


Viola Poeschel, MD, Saarland University Medical School, Homburg/Saar, Germany


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