Numerous studies have investigated the potential to use chemotherapy regimens more intensive than R-CHOP21, acknowledging that high risk patients often have inferior outcomes. The CALGB 50303 study, first presented at ASH in 2016, and now with longer-term follow up,r concludes that 6 cycles of R-CHOP21 is similar to 6 cycles of DA-R-EPOCH, with lower toxicity and similar PFS (the primary endpoint) and OS (pictured) at median follow up of 5 years.
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In the SWOG 9704 trial using 8 cycles of R-CHOP21 the PFS rate was only 54% in this high IPI risk group of DLBCL patients.r For R-CHOP patients, the 2-yr PFS = 63% in the control and 73% in the transplant group (HR, 1.56; 95% CI, 0.92 to 2.63; P=0.10). This 10% difference in PFS is not statistically significant since the study was highly underpowered to allow a meaningful comparison. By international statistical standards, need a much larger sample size.r
For patients = 60 yrs with high risk DLBCL Age-Adjusted International Prognostic Index (aaIPI = 2-3), the best results recorded to date derive from the German randomised Mega-CHOEP study.r In this study, 136 patients received R-CHOEP14 x 8, and 139 received R-Mega-CHOEP, with median follow up of 42 months. R-CHOEP14 x 8 cycles was associated with an EFS at 3 yrs of 74% and OS at 3 yrs of 85%. To date, this is the largest prospective study randomising patients to receive R-CHOEP14, with demonstrated efficacy among high risk (aa-IPI = 2-3) DLBCL patients, and illustrates that R-CHOEP14 is a reasonable treatment option in younger patients with high risk DLBCL (either with or without radiation therapy).
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In the Italian FIL study among a similar cohort of DLBCL patients with aaIPI = 2-3, 6 cycles of R-CHOP14 was associated with a PFS of 62.7%r in a matched paired analysis with patients from the Mega-CHOEP study, although not statistically significantly different R-CHOP14 was still somewhat inferior compared to 8 cycles of R-CHOEP14 (62.7% vs 73.7% respectively, P=0.1776).
A retrospective Danish study among high risk DLBCL in patients = 60 years, showed superior PFS for R-CHOEP14 compared to R-CHOP14 with rates of 70% versus 58% at 4 yrs, respectively.r
In a 2014 population-based Swedish study among DLBCL patients Age <= 70 yrs, there was no difference in survival outcomes between R-CHOP21 compared to R-CHOP14, however, R-CHOEP14 showed superior survival compared to both.r Patients had either R-CHOP-21 (n=302), R-CHOP-14 (n=872) or R-CHOEP-14 (n=157). At a median follow-up time of 49 months, 3-yr OS rates were 86.7%, 79.6% and 87.5% for R-CHOP-21, R-CHOP-14 and R-CHOEP-14, respectively. In a multivariable Cox regression model, R-CHOEP-14 was significantly superior to R-CHOP-21 (HR 0.53, CI:0.3-0.9, P=0.026) and R-CHOP-14 (HR: 0.63, CI: 0.4-1.0, P=0.048). Outcomes for R-CHOP-14 were similar to that for R-CHOP-21, consistent with findings from randomised trials.
R-CHOEP-14 with or without radiation therapy remains a treatment option for these patients, with encouraging efficacy.r