PracticeUpdate Conference Series ASH 2018

Shorter Course of CHOP + Rituximab Noninferior to Standard of Care in Younger Patients With DLBCL A shorter course of chemotherapymeans fewer adverse events and amore rapid return to normal activities.

Y ounger patients with diffuse large B-cell lymphoma (DLBCL) may not require a full six cycles of chemotherapy as guidelines currently recommend, according to results of the phase III Flyer Trial. The Flyer Trial investigators hypothesized that a lower-intensity therapeutic regimen of four cycles of CHOP (cyclophosphamide, doxorubicin, vin- cristine, and prednisone) plus six applications of rituximab would be non-inferior to the standard- of-care six cycles of CHOP in younger patients with DLBCL. To test their hypothesis, the investigators enrolled patients aged 18 to 60 years who had stage I or II DLBCL that was considered to be low-risk. A total of 592 patients were enrolled between December 2005 and October 2016: 295 patients were ran- domized to receive the six-cycle CHOP regimen, whereas 293 patients were randomized to receive four cycles of CHOP with rituximab. Patients were enrolled from multiple European centers in Germany, Denmark, Norway, Italy, and Israel. There were no significant differences in demographics (median age 48 years) or protocol adherence between study arms. After a median 66 months of follow-up, the inves- tigators found that the 3-year progression-free survival (PFS) rates in both study arms were not significantly different from each other (94% with the six-cycle regimen vs 96% with the four-cycle regimen plus rituximab, P = .760). The study met its primary endpoint, namely a less than 5.5% impairment in PFS with the four-cycle CHOP plus rituximab regimen relative to the six- cycle standard-of-care regimen (lower limit of 95% confidence interval in difference between treatment arms = 0%). The investigators found that the 3-year event-free survival rates were identical between treatment arms (both 89%), with events including progressive disease, relapse, or death.

Dr. Viola Poeschel

Overall survival (OS) also did not significantly differ between treatment arms. Whereas 3-year OS was 98% in patients receiving six cycles of CHOP, the 3-year overall survival rate in patients receiving four cycles of CHOP plus rituximab was 99%. “Chemotherapy can be reduced without compro- mising prognosis in this population,” concluded study presenter Viola Poeschel, MD, of Saarland University Medical School in Homburg/Saar, Germany. Under the shorter chemotherapy regimen used in this study, patients receive chemotherapy for a total of 84 days, compared with the standard six-cycle chemotherapeutic regimen of 126 days. Dr. Poeschel suggested that the shorter duration of chemotherapy would allow patients to resume their lives more rapidly, without side effects that constrain work and home activities. “Reducing chemotherapy to four cycles also resulted in a reduction of acute adverse events by about a third, which means a significant ben- efit for patients,” Dr. Poeschel told Elsevier’s PracticeUpdate . Whereas 1295 adverse events were observed among the 295 patients who received the longer chemotherapy course, 835 adverse events were observed among the 293 patients receiving the shorter course with rituximab. Dr. Poeschel said she believes that the shorter, non-inferior chemotherapy regimen used in this study will become the new standard of care for younger, low-risk DLBCL patients.

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PRACTICEUPDATE CONFERENCE SERIES • ASH 2018