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Alemtuzumab and DHAP (A-DHAP) is effective for relapsed peripheral T-cell lymphoma, unspecified: interim results of a phase II prospective study
Prognosis of relapsed peripheral T-cell lymphomas (PTCLs) is poor, and the optimal salvage therapy is still not determined. The efficacy of alemtuzumab (Campath-1H®, Bayer-Schering, Berlin, Germany), a humanized anti-CD52 mAb, was previously reported for relapsed or refractory PTCLs because CD52 antigen is present on normal and pathologic T cells [1, 2]. Thus, we designed a new salvage regimen combining alemtuzumab with dexamethasone, cisplatin and cytarabine (A-DHAP). We enrolled 16 patients with relapsed or refractory PTCLs in this multicenter prospective phase II study, and the treatment protocol was summarized in Figure 1.
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The characteristics and treatment outcomes of patients were presented in Table 1. The objective response rate was 50.0% [four complete response (CR) which is defined as complete disappearance of lesion, four partial response (PR) which is defined as >50% reduction of lesion], and especially peripheral T-cell lymphoma, unspecified (PTCL-U) showed higher response (85.7%: three CR, three PR) than extranodal NK/T cell lymphoma (ENKTCL, 14.3%, 1 PR). These are consistent with previous reports showing better responses in PTCL-U than ENKTCL [1, 3]. For autologous stem-cell transplantation (ASCT), we could successfully harvest stem cells except one patient. The median overall survival (OS) was 6.0 months (95% confidence interval 3.51–8.49 months) while responders to A-DHAP showed a better OS than nonresponders (P = 0.038). Grade 3/4 leukopenia was observed in 13 patients (81.2%), but anemia and thrombocytopenia were less severe. Cytomegalovirus (CMV) reactivation was documented in five patients including one CMV colitis (patient 6) and one CMV pneumonia (patient 3).
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However, we experienced several unexplained deaths as follows. One patient died due to hepatitis B virus-induced hepatic failure (patient 9), although he was negative for hepatitis surface antigen before treatment. More than 3 months after the last dose of A-DHAP, three patients died due to respiratory failure; two patients died due to pneumonia (patient 5 and 13) and one due to diffuse alveolar hemorrhage that occurred after ASCT (patient 16). Although the causes of death are not clear, alemtuzumab-induced immune suppression might be related with these fatal outcomes. In this study, myelosuppression and infectious complications including CMV reactivation were the major toxic effects, and these are similar to previous studies with alemtuzumab [1, 3, 4]. Alemtuzumab is known to suppress immunity including the depletion of CD4 and CD8 T cells as well as B cells [5]. Thus, this alemtuzumab-induced B-cell and T-cell depletion might last longer than expected, and it might result in serious adverse events in this study. Therefore, because of a substantial incidence of serious adverse events, we modified the protocol of this phase II study as follows. Alemtuzumab was given i.v. with an escalated dose: 10 mg on day –1 and 30 mg on day 1, and DHAP was the same as previous regimen.
In summary, alemtuzumab plus DHAP might be effective salvage chemotherapy for patients with PTCL-U. However, careful monitoring of immune status is warranted to prevent infectious complications.
1 Division of Hematology–Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul
2 Department of Internal Medicine, Korea University Medical Center, Seoul
3 Department of Oncology
4 Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul
5 Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
* (E-mail: wskimsmc{at}skku.edu)
references
1. Enblad G, Hagberg H, Erlanson M, et al. A pilot study of alemtuzumab (anti-CD52 monoclonal antibody) therapy for patients with relapsed or chemotherapy-refractory peripheral T-cell lymphomas. Blood (2004) 103:2920–2924.
2. Salisbury JR, Rapson NT, Codd JD, et al. Immunohistochemical analysis of CDw52 antigen expression in non-Hodgkin's lymphomas. J Clin Pathol (1994) 47:313–317.
3. Kim JG, Sohn SK, Chae YS, et al. Alemtuzumab plus CHOP as front-line chemotherapy for patients with peripheral T-cell lymphomas: a phase II study. Cancer Chemother Pharmacol (2007) 60:129–134.[CrossRef][Web of Science][Medline]
4. Gallamini A, Zaja F, Patti C, et al. Alemtuzumab (Campath-1H) and CHOP chemotherapy as first-line treatment of peripheral T-cell lymphoma: results of a GITIL (Gruppo Italiano Terapie Innovative nei Linfomi) prospective multicenter trial. Blood (2007) 110:2316–2323.
5. Keating MJ, Flinn I, Jain V, et al. Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study. Blood (2002) 99:3554–3561.
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