Minimal Renal Toxicity after Rituximab DHAP with a Modified Cisplatin Application Scheme in Patients with Relapsed and Refractory Diffuse Large B-Cell Lymphoma

BACKGROUND: Rituximab (R) in combination with DHAP is a widely accepted salvage regimen in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). DHAP combines cisplatin (100 mg/m²) typically administered intravenously (i. v.) by continuous infusion over 24 hours, followed on day 2 by cytarabine (2 g/m²) in a 3-hour infusion repeated after 12 hours, and oral administration of dexamethasone (40 mg/d) for 4 consecutive days. A common adverse effect of this protocol consists of renal toxicity which may result in dose reduction or treatment discontinuation. Therefore novel approaches to overcome renal toxicity of R-DHAP are urgently warranted. Assuming that a lower single dose of cisplatin over several days would reduce renal toxicity, our institution has chosen to administer cisplatin at a dosage of 25 mg/m²per day as a 3-hour infusion over 4 consecutive days. In this study we systematically examine efficacy and renal toxicity of this modified R-DHAP regimen.

METHODS: We retrospectively analyzed data of 122 patients with relapsed/refractory DLBCL who were treated at our institution from July 2002 to July 2013. Patients were grouped according to the number of R-DHAP courses applied and renal function was evaluated in each subgroup. Creatinine serum levels before each R-DHAP cycle and two to three weeks after the last R-DHAP were assessed and GFR was calculated according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.

RESULTS: Overall, 256 R-DHAP cycles were administered. 31 (25%), 61 (50%), 14 (12%) and 16 (13%) patients received one, two, three or four R-DHAP courses, respectively. Dose adjustments needed to be applied in only 5 (4%) patients who in total received 11 R-DHAP courses. A step-by-step evaluation of renal function after each R-DHAP course revealed that a GFR decrease can be observed after each chemotherapy cycle. However, in none of the subgroups GFR was lower than 60 ml/min/1.73 m². In most patients, only renal impairment stage I and II was observed. Renal impairment stage III was observed in 12 patients (10%) and stage IV only in one patient (1%). The overall response rate of the modified R-DHAP protocol was 54% (CR 17%, CRu 5%, PR 32%, SD 15% and PD 29%, not known 4%).

CONCLUSION: A modified R-DHAP regimen with administration of cisplatin 25 mg/m² over 4 consecutive days is effective and safe in relapsed/refractory DLBCL and leads only to minimal renal toxicity.