Alemtuzumab Increases Serious Infections in Patients with Previously Untreated Chronic Lymphocytic Leukemia (CLL) Receiving Fludarabine-Based Therapy: A Comparative Analysis of 3 Cancer and Leukemia Group B Studies (CALGB 9011, 9712, 19901).

Infections remain a critical issue in the care of CLL patients (pts). The specific agents used and their resultant immunosuppression impact the spectrum of infection. We compared the infectious complications reported in previously untreated CLL pts enrolled on 3 sequential CALGB treatment trials. On CALGB 9011, 188 pts received single agent fludarabine (F) therapy. On CALGB 9712, 104 pts received concurrent or sequential fludarabine plus rituximab (FR). On CALGB 19901, pts were to receive 4 cycles of F, followed by 6 weeks of alemtuzumab consolidation (FA); of the 85 enrolled patients, 59 proceeded to alemtuzumab consolidation. Infections requiring hospitalization and/or parenteral antibiotics were tabulated. The 85 pts on study 19901 (FA) had significantly more of these infections during protocol therapy (32/85, 38%) compared to the 188 pts receiving F on study 9011 (43/188, 23%, p=0.01). Similarly, the 19901 study pts also had more infections than the 104 FR-treated pts on study 9712 (21/104, 20%, p=0.0007). Among the 85 pts on study 19901, 14 (16%) had infections only during the F phase of therapy, 14 (16%) had infections only during alemtuzumab consolidation, and 4 (5%) had infections during both phases of therapy. The occurrence of cytomegalovirus (CMV) and Pneumocystis (PCP) infections was also examined on these trials. No CMV and only 3 PCP infections were diagnosed among the 188 pts receiving F on study 9011. For study 9712, 3/104 pts had PCP (one on concurrent FR, two on sequential FR), and 1 pt had CMV pneumonia on sequential FR. Among pts on study 19901, one case of PCP and no cases of CMV occurred during the F phase of therapy. However, 12/59 pts developed CMV infection during alemtuzumab consolidation. Four had resolution of infection and completed alemtuzumab therapy, while 8 were hospitalized and did not complete this therapy. We conclude that the addition of rituximab to F therapy does not increase the risk or severity of infections in previously untreated CLL pts, but the use of alemtuzumab consolidation following initial F therapy does increase the overall risk of serious infectious complications, and especially CMV infections. These issues are important not only for prophylactic antimicrobial therapy and monitoring during and after therapy, but also for the potential use of alemtuzumab as a consolidation therapy to eradicate residual CLL after F treatment.