Safety and Efficacy of Mini-CHOP-R Chemotherapy for Treatment of Diffuse Large B Cell Lymphoma in Very Elderly Patients: A Quality Assurance Study

Background:

Diffuse Large B Cell Lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. Very elderly patients with DLBCL, defined as patients who are 80 years of age or older, have inferior outcomes related to co-morbid illness, poor performance status, and intolerance of full dose chemotherapy. In 2011, a phase II study of DLBCL in very elderly patients suggested a dose attenuated protocol of CHOP-R (mini-CHOP-R) reduced adverse effects while maintaining efficacy (Lancet Oncology 2011).  Based on these results, the mini-CHOP-R protocol became the standard of care for very elderly patients at the London Regional Cancer Program (LRCP) in London, Ontario, Canada in November 2011.  These patients had previously received either standard dose CHOP-R or a modified version in which the dose was reduced at the discretion of the treating clinician.  

Objective:

This quality assurance study compares safety and efficacy outcomes among very elderly patients with DLBCL treated before and after adoption of the mini-CHOP-R treatment protocol.

Methods:

Outcomes of very elderly patients with DLBCL treated at LRCP with mini-CHOP-R between November 2011 - November 2014 were compared to the outcomes of patients treated in the 5 years preceding the treatment policy change.

Results:

Seventy-three patients were evaluated in this study.  Thirty-seven patients (16M/21F; median age 83, range 80-93) treated with mini-CHOP-R comprised the study group, and thirty-six patients (16M/20F; median age 83, range 80-97) who received standard or 'clinician-modified' CHOP-R comprised the historical control group. The two groups differed in stage and ECOG status but were otherwise similar. Thirty-three (89%) study patients had advanced stage disease vs. 15 (42%) patients in the control group (p= 0.018). Thirty-three (89%) mini-CHOP-R patients had an ECOG > 1 compared to 13 (36%) controls (p=0.0013). Study patients received a median of 6 cycles of mini-CHOP-R compared to 4.28 cycles in the CHOP-R cohort (p=0.11).  Granulocyte-colony stimulating factors were used as primary prophylaxis in the majority of patients in both cohorts. Chemotherapy side effects necessitated dose reductions in 6 (16%) mini-CHOP-R patients vs. 24 (67%) control patients.  This was mainly due to the difference in febrile neutropenia, which complicated 4/178 mini-CHOP-R cycles (2%) compared to 16/181 CHOP-R cycles (9%). Cardiac complications were observed in 1 (3%) mini-CHOP-R patient, compared with 3 (8%) controls.  Response rates of mini-CHOP-R treated patients compared favorably to controls, with overall response rates of 31/37 (84%) vs. 30/36 (83%), complete responses of 20 (54%) vs. 19 (53%), and partial responses of 11 (30%) vs. 11 (31%).  Six patients in each group progressed on treatment. The 1-year overall survival and 1-year progression-free survival rates were 60% and 51% in mini-CHOP-R study group compared to 56% and 53% in control group.

Conclusions:

Results with mini-CHOP-R have been encouraging so far.  Despite the more aggressive disease (higher stage, inferior ECOG) in mini-CHOP-R patients compared to controls treated with CHOP-R, similar response rates were achieved, with fewer adverse effects and better tolerability, which is of particular importance in very elderly patients.  Longer follow up will be necessary to determine durability of responses.