On 23rd June 2017, in a Letter to the Editor of Blood Cancer Journal, Thomas E. Witzig and colleagues from the Mayo Clinic College of Medicine and Mayo Foundation, Rochester, provided an update on the results from the North Central Cancer Treatment Group (NCCTG) N1085 phase I and feasibility study (NCT01334502) of everolimus in combination with standard R-CHOP in patients with untreated DLBCL.1
Previous results from this phase I and feasibility study which were obtained at the time of the last follow up in March 2016, demonstrated that everolimus in combination with R-CHOP was safe and efficacious. At a median follow-up of 21.5 months, the Overall Response Rate (ORR) was 96% (23/24) and all patients who achieved a response also attained a functional Complete Response (CR) by Positron Emission Tomography (PET). Additionally, all twenty-four patients were event-free at 12 months and 9 patients, with sufficient follow-up data, were event-free at 24 months.2
Witzig et al., provided an update on the Event Free Survival at 24 months (EFS24 [a surrogate for long-term outcome]) of all patients (n = 24) examined as of February 2017. Additionally, they reported on the time from Diagnosis to day 1 of Treatment (DtT), which has been reported to influence the rate of achieving EFS24.3 The median follow-up for patients was 37.2 months.
- All twenty-four patients were EFS24 and alive with no relapses
- Median DtT in all patients (n = 24); 14 days (range 5–48 days)
The authors highlighted that the “results from this small study of everolimus/R-CHOP continue to be promising, especially since the median DtT of the patients on this trial was 14 days”. Recent data have demonstrated that DLBCL patients with a DtT of ≤ 14 days treated with R-CHOP would have an expected EFS24 failure rate of 44% 3 and thus the authors suggested that DtT should be used as “a stratification factor” in DLBCL patients “given its influence on EFS24”.
Witzig et al., concluded by proposing that newer trials in DLBCL patients should begin reporting EFS24 and DtT in order to allow better comparison across studies.
- Witzig T. E et al. High rate of event-free survival at 24 months with everolimus/RCHOP for untreated diffuse large B-cell lymphoma: updated results from NCCTG N1085 (Alliance). Blood Cancer J. 2017 Jun 23; 7(6): e576. DOI: 10.1038/bcj.2017.57.
- Johnston P. B. et al. Everolimus combined with R-CHOP-21 for new, untreated, diffuse large B-cell lymphoma (NCCTG 1085 [Alliance]): safety and efficacy results of a phase 1 and feasibility trial. Lancet Haematol. 2016 Jul; 3(7): e309–16 DOI: 1016/S2352-3026(16)30040-0. Epub 2016 Jun 5.
- Maurer M. et al. Time from diagnosis to initiation of treatment of DLBCL and implication for potential selection bias in clinical trials. Blood. 2016; 128: 3034.