DLBCL

R-CHOP-14 or R-CHOP-21: Which is more effective in treating elderly DLBCL patients?

In April 2017, Andrea Kühnl, from the Royal Marsden NHS Foundation Trust, London, UK, and colleagues published in Annals of Oncology the results of a sub-group analysis, with extended follow-up, of patients who were ≥60 years old from the UK NCRI R-CHOP14v21 trial.

The R-CHOP14v21 trial was a randomized phase III trial comparing R-CHOP-14 to R-CHOP-21 in 1,080 adult patients newly diagnosed with DLBCL, of which 604 were ≥60 years old.

Key Highlights:
  • Median age: 67 (60–88)
  • Both R-CHOP-21 (n = 301) and R-CHOP-14 (n = 303) arms were balanced for baseline patient characteristics, apart from BCL6 rearrangements and Double-Hit Lymphoma (DHL) status, which was higher in the R-CHOP-14 group
  • Pts that did not complete treatment: R-CHOP-21 = 24% vs. R-CHOP-14 = 15% (P = 0.01)
  • Response evaluable in 274 pts per arm
    • ORR: R-CHOP-21 = 91%, R-CHOP-14 = 91%
    • CRR: R-CHOP-21 = 67%, R-CHOP-14 = 62%
  • Median follow-up of 77.7months
  • No difference in OS or PFS reported between the two arms
    • Total 5-year OS = 69%
    • Total 3-year PFS = 71%
    • 5-year OS: ≥60yr vs. ≥70yr = 69% (95% CI: 66–73) vs. 61% (95% CI: 54–68)
    • 5-year PFS: ≥60yr vs. ≥70yr = 64% (95% CI: 60–68) vs. 58% (95% CI: 54–68)
  • AEs:
    • Grade ≥3 neutropenia: R-CHOP-21 = 62% vs. R-CHOP-14 = 36% (P<0.0001)
    • Grade ≥3 thrombocytopenia: R-CHOP-21 = 7% vs. R-CHOP-14 = 12% (P=0.05)
    • Anemia: R-CHOP-21 = 20% vs. R-CHOP-14 = 31% (P=0.001)
  • Joint analysis of pts with available molecular data from the R-CHOP-14-21 and RICOVER-60 trials concluded that MYC-R status, and DHL status has significant impact on OS in both treatment groups.
    • MYC-R: HR = 1.96 (95% CI: 1.22-3.16. (P=0.01)
    • Double-hit lymphoma: HR = 2.21; 95% CI: 1.18-4.11 (P=0.01)

The authors concluded by stating that these results showed “excellent short and long-term results with both R-CHOP-14 and R-CHOP-21 in elderly DLBCL patients” and that MYC-R and DHL status had independent prognostic significance in this population of patients treated with R-CHOP-21 or R-CHOP-14.

Abstract:

BACKGROUND: There is an on-going debate whether 2- or 3-weekly administration of R-CHOP is the preferred first-line treatment for elderly patients with diffuse large B-cell lymphoma (DLBCL). The UK NCRI R-CHOP14v21 randomized phase 3 trial did not demonstrate a difference in outcomes between R-CHOP-14 and R-CHOP-21 in newly diagnosed DLBCL patients aged 19-88 years, but data on elderly patients have not been reported in detail so far. Here, we provide a subgroup analysis of patients ≥60 years treated on the R-CHOP14v21 trial with extended follow-up.

PATIENTS AND METHODS: 604 R-CHOP14v21 patients ≥60 years were included in this subgroup analysis, with a median follow-up of 77.7 months. To assess the impact of MYC rearrangements (MYC-R) and double-hit-lymphoma (DHL) on outcome in elderly patients, we performed a joint analysis of cases with available molecular data from the R-CHOP14v21 (N=217) and RICOVER-60 (N=204) trials.

RESULTS: Elderly DLBCL patients received high dose intensities with median total doses of ≥ 98% for all agents. Toxicities were similar in both arms with the exception of more grade ≥3 neutropenia (P<0.0001) and fewer grade ≥3 thrombocytopenia (P=0.05) in R-CHOP-21 vs. R-CHOP-14. The elderly patient population had a favorable 5-year overall survival (OS) of 69% (95%CI: 65-73). We did not identify any subgroup of patients that showed differential response to either regimen. In multivariable analysis including individual factors of the IPI, gender, bulk, B2M and albumin levels, only age and B2M were of independent prognostic significance for OS. Molecular analyses demonstrated a significant impact of MYC-R (HR = 1.96; 95%CI: 1.22-3.16; P=0.01) and DHL (HR = 2.21; 95%CI: 1.18-4.11; P=0.01) on OS in the combined trial cohorts, independent of other prognostic factors.

CONCLUSIONS: Our data support equivalence of both R-CHOP application forms in elderly DLBCL patients. Elderly MYC-R and DHL patients have inferior prognosis and should be considered for alternative treatment approaches.

Reference:

1. Kühnl A. et al. Outcome of Elderly Patients with Diffuse Large B-cell Lymphoma Treated with R-CHOP: Results from the UK NCRI R-CHOP14v21 trial with combined analysis of molecular characteristics with the DSHNHL RICOVER-60 trial. Annals of Oncology. 2017 Apr 07. DOI: https://doi.org/10.1093/annonc/mdx128 [Epub ahead of print].

Expert Opinion

This investigation found no clinically relevant differences between the two chemo-immunotherapy schedules in a large cohort of older patients (n > 600). It should be noted that the population of elderly patients was defined as age ≥ 60 years. However, approximately two thirds were < 70 years and approximately 80% had ECOG 0–1. It thus can be assumed that patients over 80 years, or patients with multi-morbidity/geriatric syndromes, represented a minority in this analysis. Conclusions of this study therefore apply to elderly patients with good to moderate fitness but should be extrapolated to the much more vulnerable subgroup of elderly patients mentioned above only with great caution.