Alemtuzumab in Previously Treated Chronic Lymphocytic Leukemia Patients Who Also Had Received Fludarabine

Abstract

Alemtuzumab has significant activity in poor-prognosis, fludarabine-treated CLL patients. However, because of a relatively high incidence of opportunistic infections accompanying profound lymphopenia, future protocols should include mandatory prophylaxis.

The evolving role of Alemtuzumab in management of patients with CLL

“…However, infection rates correlated with response, with only two of eight responders developing infections, compared with eight of 16 nonresponders. 21 Similar infection rates were noted in a study by Keating et al 5,22 Perkins et al 23 retrospectively reviewed the frequency and severity of serious infections in fludarabine-refractory CLL. Of 27 patients with fludarabine-refractory disease who were receiving no therapy, 24 (89%) developed serious infections, which occurred at a median of 4 months after the onset of fludarabine refractoriness.…”

Management of infections in patients with chronic lymphocytic leukemia treated with alemtuzumab

“…In the pivotal study of alemtuzumab in patients with relapsed/refractory disease, CD19 + /CD5 + B cells and CD3 + /CD4 + and CD3 + /CD8 + T cells were significantly depressed after 4 weeks of treatment [30]; these findings were confirmed by another study that also noted a decrease in CD16 + natural killer (NK) cells [49]. The T-cell population gradually recovered to baseline levels by 36 weeks after therapy initiation [30].…”

“…In another study in patients with relapsed or fludarabine-refractory CLL, infections were reported in 42% of patients, predominantly in the non-responder group. Seven of eight non-responders developed major infections during treatment and within 35 days following treatment completion, and two of them died from infections [49]. Similarly, in the pivotal study of 93 relapsed/refractory CLL patients, 25 patients (27%) experienced grade 3/4 infectious events (27%), which occurred more frequently in non-responders than in responders (36% versus 9.7%) [30].…”

“…Importantly, several studies have shown that infectious events typically occur around the time of T-cell and neutrophil nadirs (Fig. 1) [13,30,38,40,49].…”

Monoclonal antibodies as therapeutic agents in oncology and antibody gene therapy

“…Despite that infection, prophylaxis was put in force beginning on day 8 and continuing for a minimum of 2 months after treatment, and grade 3 or 4 infections were reported in 27% of the heavily pre-treated patients, including pneumocystis and aspergillus pneumonia, systemic candidiasis, cryptococccal pneumonia and listeria meningitis leading to death in 11 patients. Based on these data and other trials [36,37], alemtuzumab received the orphan status and was approved by the FDA for the treatment of CLL refractory to fludarabine in 2001.…”