Safety and Efficacy of Dose Attentuated R-CHOP Chemotherapy for Treatment of Diffuse Large B Cell Lymphoma in the Very Elderly: A Cohort Study

Background: Diffuse Large B Cell Lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, and is frequently diagnosed in elderly patients. Elderly patients with DLBCL are known to have worse outcomes than younger patients with the same disease, in part due to comorbidities and poor performance status that may decrease their ability to tolerate treatment. A recent phase II study (Lancet Oncology 2011;12:460-8) demonstrated that patients with DLBCL who were older than 80 years of age had excellent tolerability while still maintaining efficacy when treated with an attenuated dose of R-CHOP called “R-mini-CHOP”. This paper prompted a change in treatment policy of very elderly patients with DLBCL at the London Regional Cancer Program. In November 2011, we began treating all DLBCL patients > 80 (and select patients aged 70-79 with significant comorbidities) with the R-mini-CHOP regimen rather than with standard R-CHOP or a ‘randomly dose-attenuated version’ of R-CHOP, which had been our practice prior to the policy change.

Objective: This quality assurance study was undertaken in order to monitor and ensure the safety and efficacy of this practice change.

Methods: Data was collected prospectively on all elderly patients with DLBCL who were initiated on R-mini-CHOP between November 2011 and January 2013. A retrospective chart review was also performed on patients > 80 treated at our centre in the preceding 10 years, after R-CHOP became standard treatment in elderly patients with DLBCL. We used 16 patients > 80 who received full dose R-CHOP between January 2010 and November 2011 as a historical control group for our prospective cohort.

Results: Since November 2011, 17 patients (median age 81, range 71-90) have been treated with R-mini-CHOP and were enrolled in this quality assurance study. All 17 patients had stage III or IV disease. In contrast, only 6/16 patients in the retrospective group were advanced stage (p=0.00004). 12/17 R-mini-CHOP patients (70.6%) had an ECOG > 1, vs. 7/16 R-CHOP patients (43.8%, p=0.070). No dose modifications have been required in patients on R-mini-CHOP. 11/16 patients on R-CHOP underwent dose reductions due to side effects of chemotherapy. The majority of patients in both cohorts received primary prophylaxis with neupogen/neulasta. Five patients remain on R-mini-CHOP, all showing evidence of clinical response. Follow-up is too short to report on PFS or OS, but overall response rate thus far is 10/12 (83%) with 7 CRs (58.3%) and 3 PRs (25%). This compares favorably to the retrospective group who had an ORR of 13/16 (81%, p=0.30), 7 CRs (43.8%) and 6 PR’s (37.5%). One patient in each group had stable disease at the end of treatment. One mini-R-CHOP patient progressed on treatment and ultimately died of lymphoma. In the retrospective cohort, 4 deaths occurred secondary to infectious complications of chemotherapy during treatment period.

C onclusions: Results with R-mini-CHOP have been encouraging so far. Despite the more aggressive disease (higher stage, inferior ECOG) in our R-mini-CHOP patients compared to the historical controls treated with R-CHOP, similar response rates are being achieved, with fewer adverse effects and better tolerability. Ongoing enrollment and longer follow-up will further help define the role of R-mini-CHOP in the very elderly patient population.

Updated results with longer followup will be presented at the meeting.