A Phase II Trial of Dexamethasone, High-Dose Cytarabine, and Cisplatin (DHAP) in Combination with Rituximab as Salvage Treatment for Patients with Refractory or Relapsed Aggressive Non-Hodgkin’s Lymphoma.

Purpose: With commonly used salvage chemotherapy regimens like DHAP, response and overall survival rates are unsatisfactory. We designed a multicenter phase II trial to evaluate the safety and efficacy of the combination of rituximab with the DHAP regimen in patients who relapsed after or were resistant to a CHOP-like regimen.

Methods: 61 patients with relapsed or resistant aggressive B-cell NHL were included in this trial so far. The median age was 61,5 years. 39 patients were in first relapse; 21 had recurrence during the first 12 months after treatment. 5 patients had second or subsequent relapse, 17 had primary refractory disease. Treatment consisted of rituximab infusions (375 mg/m2 per dose) on day 1 followed by dexamethasone 40 mg d3–6 (d 3–5 in first cycle), cytarabine 2 x 2000 mg/m2 d 4 (2 x 1000 mg/m2 in first cycle), 2 x 1000 mg/m2 for patients > 60 years of age (2 x 500 mg/m2 in first cycle), and cisplatin 25 mg/m2 d 3–6 (d3–5 in first cycle) for a maximum of 4 cycles. When hematological toxicity did not allow continuation of chemotherapy on day 22, rituximab was given as single agent on day 22 and the next cycle was postponed until day 29.

Results: The overall response rate in evaluable patients was 54.0%. 29.0% of patients achieved a complete response, 25% of patients had a partial response, 15.0% of patients had stable disease. 31.0% of patients showed progressive disease. Patients in first relapse achieved an overall response of 67.0 % as opposed to only 27.0% in patients with refractory disease. Grade 3/ 4 nausea and vomiting were the only severe toxicities attributed to rituximab in one patient. Main toxicities were neutropenia and thrombocytopenia. Grade 3/ 4 nephrotoxicity occured in 2 patients. Survival data will be presented at the meeting.

Conclusions: Interim analysis of the data suggests that the combination of rituximab with the DHAP regimen in the treatment of relapsed or refractory aggressive lymphoma is feasible and effective. In view of the unfavorable prognostic factors in our patient population, response rates (ORR = 54%) are encouraging and warrant further investigation.