On Monday 3 December 2018, Oral Session 626took place at the 60 thAmerican Society of Hematology (ASH) Annual Meeting, San Diego, CA. During that session, Abstract #781with the results of the FLYER trial were presented by Viola Poeschelfrom Saarland University Medical School, Saarland, Germany.
In this phase III trial, the investigators hypothesized that four cycles of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) plus two more rituximab infusions are similarly efficacious to the current standard of care for young non-Hodgkin lymphoma (NHL) patients, of six R-CHOP cycles. The primary endpoint of the trial was 3-year progression-free survival (PFS). Secondary endpoints included, response rates, event-free survival (EFS), overall survival (OS), and safety.
Study design & baseline characteristics
- Trial duration: December 2005 to October 2016
- Evaluable patients for this analysis were N = 588 patients with aggressive B-cell NHL between 18−60 years, stage I−II disease, age-adjusted International Prognostic Index (aaIPI) of zero, no bulky disease (maximum diameter < 7.5 cm)
- Dosing:
- Six R-CHOP cycles (n = 295)
- Four R-CHOP cycles plus two rituximab (2 x R) infusions (n = 293)
- Median age (range) = 48 (18−60) of the total cohort
- No differences in demographics (age, sex, disease stage, aaIPI score, bulky disease incidence, extranodal lymphoma involvement) protocol adherence, or toxicity were observed between the two arms
- Three-year PFS prediction for the 6 x R-CHOP arm was 93% and it was planned to tolerate an impairment of 5.5% by reducing the number of courses to 4 x R-CHOP + 2 x R to prove non-inferiority with a power of 80% and an alpha-error of 5% (one-sided)
Results
- Median follow-up: 66 months
- At 36 months, PFS was:
- 6 x R-CHOP arm: 94% (95% CI, 91−97%) from n = 295
- 4 x R-CHOP + 2 x R arm: 96% (95% CI, 94−99%) from n = 293
- Complete response (CR/CRu) rates:
- 6 x R-CHOP arm: 92% from n = 295
- 4 x R-CHOP + 2 x R arm: 91% from n = 293
- Partial response (PR) rates:
- 6 x R-CHOP arm: 2% from n = 295
- 4 x R-CHOP + 2 x R arm: 1% from n = 293
- Therapy-associated death occurred in 1% of patients in the 6 x R-CHOP arm and in none in the 4 x R-CHOP + 2 x R arm
- At 36 months and a median follow-up of 65 months, EFS was:
- 6 x R-CHOP arm: 89% (95% CI, 85−92%) from n = 295
- 4 x R-CHOP + 2 x R arm: 89% (95% CI, 86−93%) from n = 293
- At 36 months and a median follow-up of 67 months, OS was:
- 6 x R-CHOP arm: 98% (95% CI, 96−99%) from n = 295
- 4 x R-CHOP + 2 x R arm: 99% (95% CI, 98−100%) from n = 293
- With respect to relapse rate there was no significant difference between the two arms, with 4% (95% CI, 2−7%) of patients in the 4 x R-CHOP + 2 x R arm relapsing versus5% (95% CI, 3−8%) in the 6 x R-CHOP group
Safety
- The most common hematological adverse events (AEs) in both arms were:
- Leukocytopenia
- Anemia
- Thrombocytopenia
- Any grade leukocytopenia occurred in:
- 6 x R-CHOP arm: 237 out of 295 patients
- 4 x R-CHOP + 2 x R arm: 171 out of 293 patients
- Grade ≥ 3 leukocytopenia occurred in:
- 6 x R-CHOP arm: 110 out of 295 patients
- 4 x R-CHOP + 2 x R arm: 80 out of 293 patients
- Any grade anemia occurred in:
- 6 x R-CHOP arm: 172 out of 295 patients
- 4 x R-CHOP + 2 x R arm: 107 out of 293 patients
- Grade ≥ 3 anemia occurred in:
- 6 x R-CHOP arm: 8 out of 295 patients
- 4 x R-CHOP + 2 x R arm: 2 out of 293 patients
- Any grade thrombocytopenia occurred in:
- 6 x R-CHOP arm: 17 out of 295 patients
- 4 x R-CHOP + 2 x R arm: 16 out of 293 patients
- Grade ≥ 3 thrombocytopenia occurred in:
- 6 x R-CHOP arm: 7 out of 295 patients
- 4 x R-CHOP + 2 x R arm: 5 out of 293 patients
- There was approximately a 1/3 reduction in non-hematological AEs in the 4 x R-CHOP + 2 x R arm when compared to the 6 x R-CHOP group
Conclusions
- In younger patients with aggressive B-cell non Hodgkin lymphoma (NHL) and favorable prognosis, efficacy (EFS, PFS, and OS) with four cycles of R-CHOP plus two cycles of rituximab is non-inferior to the standard of care of six R-CHOP cycles
- Chemotherapy could be spared without compromising prognosis in this population