Alemtuzumab and DHAP (A-DHAP) Is An Effective Salvage Therapy for Peripheral T-Cell Lymphoma, Unspecified: Interim Results of a Phase II Prospective Multicenter Study

Purpose: The prognosis for relapsed or refractory peripheral T-cell lymphomas (PTCLs) is extremely poor, and there is still no consensus on the optimal salvage therapy. Alemtuzumab (Campath-1H^®, Bayer-Schering, Berlin, Germany) is a humanized immunoglobulin G1 anti-CD52 monoclonal antibody. Considering the expression of CD52 antigen on the surface of T-cell lymphoma cells, alemtuzumab could be a suitable agent for the treatment of PTCLs. A previous pilot study showed the efficacy of alemtuzumab as a single agent for patients with relapsed or refractory PTCLs. Thus, we designed a new chemotherapy regimen, A-DHAP, consisting of alemtuzumab and DHAP (dexamethasone, cisplatin, and cytarabine) to augment the efficacy of alemtuzumab against PTCLs. Herein, we report the interim results of phase II prospective multicenter study using the A-DHAP regimen in patients with relapsed or refractory PTCLs.

Patients and Methods: We enrolled 16 patients between the ages of 18 and 65 years who had histologically confirmed PTCLs, excluding ALK-positive anaplastic large cell lymphoma. Patients were required to have failed primary treatments such as anthracycline-containing regimens. Failure was defined as a relapse from previous confirmed complete response (CR) or progress during treatment. Each patient received DHAP plus an escalated dosage of alemtuzumab (10 mg on day -1 and 30 mg on day 1 and 2) every 3 weeks for up to 3 cycles. Responders then received high-dose chemotherapy followed by autologous stem cell transplantation (ASCT).

Results: At relapse or progression after previous therapy, 13 patients presented as stage III or IV (81.3%). However, 11 patients belonged to low or low-intermediate IPI (international prognostic index) risk as they were less than 60 years old, had normal serum LDH and good performance status. Peripheral T-cell lymphoma, unspecified (PTCL-U) and extranodal NK/T cell lymphoma, nasal type (ENKTCL) were the dominant histological subtypes (14/16, 87.6%). The median treatment was 2 cycles (range 1–3 cycles). Seven patients completed the planned 3 cycles of A-DHAP. Eight patients showed an objective response including four CR and four PR, while seven patients showed PD (Progressive disease), and one patient had SD (Stable disease) after the 3^rd cycle. Thus, the objective response rate was 50.0% (8 of 16 patients). When we analyzed the response according to the histological type, the objective response rate was much higher for PTCL-U (85.7%: 3 CR, 3 PR) than for ENKTCL (14.3%, 1 PR). Seven patients could receive autologous stem cell transplantation (ASCT); five patients after objective response and two patients after other salvage treatments. The median CD34+ cell count was more than 3.79×10⁶/kg (range, 2.30 – 5.90×10⁶/kg), and there was no engraftment failure. However, one patient could not receive ASCT because the yield of CD34+ cell count was less than the minimal requirement (2.00×10⁶/kg) although his complete blood cell count was within normal range after the completion of three cycles of A-DHAP chemotherapy. The median overall survival (OS) after enrollment in the study was 6.0 months (95% confidence interval 3.51–8.49 months). Responders to A-DHAP showed a better OS than non-responders (P = 0.038). The most frequent side effects were grade 3/4 leukopenia and infectious complications including cytomegalovirus reactivation, hepatitis B virus infection and pneumonia.

Conclusions: The combination of alemtuzumab plus DHAP might be an effective salvage chemotherapy regimen for PTCL-U patients. However, careful monitoring and dosage modification are warranted to prevent treatment-related toxicity.