SAN DIEGO, CA—A first-line regimen that incorporated gemcitabine with rituximab, cyclophosphamide, vincristine, and prednisolone (R-GCVP) for the treatment of patients with diffuse large B-cell lymphoma (DLBCL) ineligible for anthracycline-containing chemotherapy delivered “excellent overall response rates” in this challenging population, a Phase 2 study presented during the 53rd American Society of Hematology Annual Meeting and Exposition has found.

Paul Fields, MD, PhD, of Guys and St. Thomas Hospital, London, UK, and colleagues conducted a prospective multicenter trial in patients with DLBCL who had an ECOG performance status of 0–3 and either an ejection fraction <50%, or an ejection fraction ≥50% but with the presence of attendant significant comorbidities, including ischemic heart disease, hypertension, and/or diabetes mellitus.

Gemcitabine, a nucleoside analog that has proven efficacy in the relapse setting in patients with non-Hodgkin’s and Hodgkin’s lymphoma, was given in combination wtih rituximab 375mg/m2 IV, cyclophosphamide 750mg/m2 IV, and vincristine 1.4mg /m2 IV on Day 1; and prednisolone 100mg orally on Days 1–5. Gemcitabine was initiated at 750mg/m2 IV on Days 1 and 8. If tolerated, the dose was sequentially escalated from 750mg/m2 in Cycle 1 to 875mg/m2 in Cycle 2 then 1,000mg/m2 in Cycle 3, with the dose maintained at 1,000mg/m2 for Cycles 4–6. Cycles were repeated every 21 days for six cycles. Pegfilgrastim 6mg was administered subcutaneously on Day 9 of each cycle.

The primary endpoint was an overall response rate (ORR) of >40%, assessed by CT scan at the end of treatment according to Cheson criteria. Secondary endpoints were progression-free survival (PFS) and overall survival (OS).

From April 2008 to July 2010, 62 patients were recruited from 32 sites in the UK. Median age was 76 years (range 52–90); 48 patients (77%) were >70 years and 66% were male. Stage III/IV disease was the diagnosis in 43 patients (69%) and 46 (72%) had high–intermediate or high International Prognostic Index (3–5) disease. ECOG performance status was ≥2 in 50% of patients. Twenty-seven patients (44%) had a left ventricular ejection fraction (LVEF) of ≤50%. Significant comorbidities were observed among the 34 patients with an LVEF ≥50%; of these, 22 (65%) had multiple comorbidities.

Of the 62 patients, 44 (70%) received ≥3 cycles of treatment, 29 (47%) of whom received the full six cycles. The remaining 18 patients had treatment terminated early due to disease progression (n=2), toxicity (n=5), death (n=6), patient choice (n=1), or other reason (n=4). Gemcitabine was escalated to the full 1,000mg/m2 dose in 67% of the 44 patients who received ≥3 cycles of treatment and Day 8 gemcitabine was delivered in 215 of the 250 treatment cycles (86%).

At end of treatment for all 62 patients, ORR (complete response + unconfirmed complete response + partial response), was 60%. For patients who received ≥3 cycles of treatment (n=44), ORR was 79.5%. No significant difference was observed in ORR between those with an LVEF ≤50% vs those with an LVEF >50% (71% vs 53%, P=0.155).

At a median follow-up of 18.2 months, the one-year PFS rate for all patients was 52.9% (95% CI: 39.4–64.8). The one-year OS rate was 62.4% (95% CI: 48.5–73.6). For those with an LVEF <50%, OS was 70.8% (95% CI: 48.4–84.9); in the LVEF ≥50% group, OS was 55.9% (95% CI: 37.1–71). Grade 3/4 hematological toxicity was observed in 54.1% of patients and Grade 3/4 infection in 24.6%; rate of death related to infection for the entire cohort was 11%.

“The efficacy attained in this difficult group of patients provides a platform for testing the regimen in subsequent randomized Phase 2 and Phase 3 studies to confirm its efficacy,” Dr. Fields concluded.