A Randomized Trial of Valacyclovir Versus Valganciclovir To Prevent CMV Reactivation in Patients with CLL Receiving Alemtuzumab.

Alemtuzumab is an effective treatment for patients with CLL, but is an immunosuppressive antibody that depletes normal T-cells as well as B-cells. Prophylaxis for HSV and PCP is standard with this agent. About 25% of patients will experience CMV reactivation, manifested by fever and antigenemia. We conducted a randomized trial wherein patients being treated with an Alemtuzumab-containing regimen received either prophylaxis with valacyclovir 500 mg po daily, or valganciclovir 450 mg po b.i.d. CMV antigen was monitored every 2 weeks for 12 weeks. The study design planned to enroll 128 patients, but stopping rules for early termination were met. Forty-six patients were entered, six were inevaluable. Median age was 58 years (range 25–83); median number of prior therapies was 2 (0–10). Diagnoses included CLL (29), T-PLL (3), HCL (1), ATLL (1), marginal zone leukemia (1), LGL leukemia (2), ALL (1), T-cell lymphoma (2). Of patients with active CLL (some received treatment for MRD), Rai stage was I–II = 13, III–IV = 10. Patients received varying Alemtuzumab-containing regimens including single agent (5), or combined with: Rituximab (2), Pentostatin (6), FCR (23), or Hyper-CVAD (4). Seven of 20 patients enrolled on the valacyclovir arm experienced symptomatic CMV reactivation with the number of CMV antigen containing cells ranging from 19–651. None of the 20 patients randomized to valganciclovir experienced symptomatic CMV reactivation (p=0.004). One patient receiving valganciclovir had 6 CMV antigen + cells at 2 weeks but was asymptomatic and continued on prophylaxis; repeat testing at 4 weeks showed 0 Ag + cells. Given the heterogeneity of regimens and the frequency of myelosuppression expected, it is uncertain as to whether valganciclovir increased the incidence of myelosuppression. In conclusion, this agent was highly effective for prophylaxis of CMV in patients receiving Alemtuzumab. Further studies may address whether the use of this antibiotic with single-agent Alemtuzumab increases the incidence of myelosuppression and whether a lower dose of valganciclovir (450 mg daily) would be as effective in prophylaxis.