Efficacy and Safety of Reduced Dose Intensity R-CHOP in Elderly Patients with Diffuse Large B Cell Lymphoma

Chemotherapy with curative intent should be given to all patients with diffuse large B-cell lymphoma (DLBCL), however, elderly patients often have a variety of co-morbidities and poor functional status resulting in high rate of adverse events related to treatment such as anthracycline-related cardiotoxicity or hematologic toxicities. Although primary prophylactic granulocyte colony-stimulating factor (G-CSF) is often used to prevent severe neutropenia, pharmaco-economic arguments exist and it is not available for considerable populations worldwide.

Therefore, we aimed to assess the efficacy and safety of the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone with rituximab (R-CHOP) with reduced doses of cyclophosphamide and doxorubicin by 25% in elderly patients with DLBCL.

Medical records of a total of 118 patients aged ≥65 years with DLBCL, newly diagnosed between September 2007 and March 2012, were retrieved from the database. All patients received R-CHOP chemotherapy every 3 weeks with reduced doses of cyclophosphamide (562.5 mg/m²) and doxorubicin (37.5 mg/m²). No patient received primary prophylactic G-CSF, however, it was allowed to those who suffered from febrile neutropenia or grade 4 neutropenia (ANC<500/μl) during treatment. Doses of cyclophosphamide and doxorubicin were reduced by additional 25% in those patients.

The median age was 72 years (range 65–85) at diagnosis and the cohort included 9 (7.6%) very elderly patients (≥80 years). The Ann Arbor stage was stage I or II in 43 patients (36.4%) and III or IV in 75 (63.6%). The international prognostic index (IPI) scores were 0–1 in 31 patients (26.3%), 2 in 21 (17.8%), 3 in 25 (21.2%), and 4–5 in 41 (34.8%). Performance status was good (ECOG <2) in all the patients. The median number of cycle was 6 (range 1–8). Eighty-seven patients (73.7%) completed the planned cycles of chemotherapy. Thirty-one patients failed to finish chemotherapy owing to intolerance to treatment (35.5%), infection (12.9%), other toxicities (25.8%), or follow-up loss (25.8%).

The overall response rate (ORR) was 78% with a complete response (CR) rate of 65.3%. With a median follow-up duration of 22.9 months (range 4.5–58.7), 2-year progression-free survival (PFS) and overall survival (OS) were 60.6% and 68.7% respectively.

Grade 3/4 neutropenia and thrombocytopenia were observed in 55 (46.6%) and 12 patients (10.2%), respectively. Thirty-two patients (27.1%) experienced febrile neutropenia and 41 patients (34.7%) required additional dose reduction. Six patients (5.1%) suffered from life-threatening toxicities and eventually died.

The R-CHOP chemotherapy with reduced dose of cyclophosphamide and doxorubicin doesn't seem to attenuate the efficacy of R-CHOP chemotherapy in the elderly patients when compared with the original report (Coiffier et al, NEJM 2002). However, toxicities still matter despite upfront dose reduction. Tailored strategies or other regimens with better toxicity profiles are in need for these patients.

No relevant conflicts of interest to declare.