A pilot study of alemtuzumab (anti-CD52 monoclonal antibody) therapy for patients with relapsed or chemotherapy-refractory peripheral T-cell lymphomas

Abstract

Patients with peripheral T-cell lymphomas (PTLs) have an extremely poor prognosis when relapsed or refractory to conventional chemotherapy. We have studied alemtuzumab, a humanized anti-CD52 monoclonal antibody, as therapy for patients with heavily pretreated and refractory PTL. Fourteen patients entered the study. All had clinical stage III or IV disease. Patients received a rapidly escalating dosage of alemtuzumab during the first week and, thereafter, 30 mg intravenously 3 times per week for a maximum of 12 weeks. Trimethoprim/sulphamethoxazole and valaciclovir prophylaxis was given to all patients. The overall response rate was 36% (5 of 14). Three patients achieved a complete remission (CR) and 2 patients a partial remission. The durations of the CRs were 2, 6, and 12 months, respectively. Toxicity included cytomegalovirus reactivation in 6 patients, which was successfully treated with ganciclovir or foscarnet; pulmonary aspergillosis in 2 patients; and pancytopenia in 4 patients. Epstein-Barr virus-related hemophagocytosis was observed in 2 patients. Five patients died of causes related to the treatment, in combination with advanced disease. We conclude that alemtuzumab is active when used in patients with advanced, heavily pretreated PTL, although it is associated with significant hematologic toxicity and infectious complications. Further studies are warranted in younger patients and patients with less advanced disease. (Blood. 2004;103: 2920-2924)

Cutaneous T‐cell lymphoma: 2011 update on diagnosis, risk‐stratification, and management

“…Similar results, with no infectious complications, were recently reported in a small cohort of patients treated with modified, low-dose, subcutaneous alemtuzumab for 6 weeks [321]. In addition to hematologic toxicity, conventionally dosed alemtuzumab in advanced-stage MF/SS is associated with a high incidence of infectious complications [319,320,[322][323][324][325]. Overall, infectious complications have been observed in twothirds of treated patients, most of which are bacterial, including sepsis.…”

The Outcome of HyperCVAD Combined with Alemtuzumab for the Treatment of Aggressive T-Cell and NK-Cell Neoplasms

“…It is a humanized monoclonal antibody that targets CD52, a cell surface protein present at high density on most normal and malignant B and T lymphocytes. As a single agent, alemtuzumab has been used to treat pretreated cutaneous/PTCL with overall response rate (ORR) of 36-60% [28][29][30]. A higher ORR of 50% was observed in the treatment of mycoses fungoides [30].…”

Evolving therapy of peripheral T-cell lymphoma: 2010 and beyond

“…Alemtuzumab, an anti-CD52 MAb, has been shown to have activity in heavily treated patients with PTCL with an ORR of 36 52% [Piccaluga et al 2007;Zinzani et al 2005;Enblad et al 2004]. Toxicities including opportunistic infections and pancytopenia occurred at a high rate and led to premature closure of one study [Enblad et al 2004].…”

“…Toxicities including opportunistic infections and pancytopenia occurred at a high rate and led to premature closure of one study [Enblad et al 2004]. Alemtuzumab has been used in combination with CHOP or EPOCH (etoposide, prednisone, vincristine, cyclophophamide, and doxorubicin) with some success in PTCL, with half of patients achieving a complete response [Gallamini et al 2007;.…”