Valganciclovir prevents cytomegalovirus reactivation in patients receiving alemtuzumab-based therapy.
Alemtuzumab is an immunosuppressive antibody that depletes normal T cells and B cells. Prophylaxis for herpes virus and Pneumocystis carinii is standard with this agent. Approximately 20% to 25% of patients will experience cytomegalovirus (CMV) reactivation. We conducted a randomized trial wherein patients being treated with an alemtuzumab-containing regimen received prophylaxis with either valaciclovir 500 mg orally daily or valganciclovir 450 mg orally twice daily. The study design planned to enroll 128 patients, but stopping rules for early termination were met. Forty patients were evaluable. Median age was 58 years (range, 25-83 years); median number of prior therapies was 2 (range, 0-10). Diagnoses included chronic lymphocytic leukemia (29), T-cell prolymphocytic leukemia (3), hairy cell leukemia (1), adult T-cell leukemia/lymphoma (ATLL) (1), marginal zone leukemia (1), large granular lymphocyte leukemia (2), acute lymphoblastic leukemia (1), and T-cell lymphoma (2). Patients received various alemtuzumab-containing regimens, including single agent (5) or combined with: rituximab (2), pentostatin (6), fludarabine, cyclophosphamide, and rituximab (23), or fractionated cyclophosphamide, vincristine, adriamycin, and dexamethasone (hyper-CVAD) (4). Seven of 20 patients enrolled on the valaciclovir arm experienced CMV reactivation. None of the 20 patients randomized to valganciclovir experienced CMV reactivation (P = .004). In conclusion, this agent was highly effective for prophylaxis of CMV reactivation in patients receiving alemtuzumab. This trial was registered at www.ClinicalTrials.gov as #NCT00562770.
Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. sobrien@mdanderson.org
Susan
S
O'Brien
Farhad
F
Ravandi
Todd
T
Riehl
William
W
Wierda
Xuelin
X
Huang
Jeffrey
J
Tarrand
Brandi
B
O'Neal
Hagop
H
Kantarjian
Michael
M
Keating
D000293:Adolescent; D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D003587:Cytomegalovirus / Q000187:drug effects / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000517:prevention & control*; D005260:Female; D015774:Ganciclovir / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008212:Lymphocyte Depletion; D008297:Male; D018579:Patient Selection; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D000077562:Valganciclovir; D014775:Virus Activation / Q000187:drug effects / Q000502:physiology*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D000074323:Alemtuzumab; D000077562:Valganciclovir; D015774:Ganciclovir