Management guidelines for the use of alemtuzumab in chronic lymphocytic leukemia

Abstract

The consensus views of an expert roundtable meeting are presented as updated management guidelines for using alemtuzumab in chronic lymphocytic leukemia. Since the publication of previous management guidelines in 2004, clinical experience with alemtuzumab has grown significantly, especially regarding its efficacy and safety, management of cytomegalovirus (CMV) reactivation, identification of patient subgroups likely to benefit from alemtuzumab therapy and subcutaneous administration of alemtuzumab. The updated recommendations include (1) alemtuzumab monotherapy can be safely used as first-line therapy; (2) suitable patient subgroups for alemtuzumab therapy include elderly patients, patients with 17p deletion, patients with refractory autoimmune cytopenias and patients with profound pancytopenia at baseline due to heavily infiltrated bone marrow; (3) alemtuzumab treatment should be continued for 12 weeks (36 doses) whenever possible, and bone marrow examination may be considered at week 12 to evaluate response; (4) monitoring CMV reactivation by weekly PCR is mandated during therapy; when CMV reactivation becomes symptomatic or viremia increases, alemtuzumab therapy should be interrupted and anti-CMV therapy started; (5) subcutaneous administration is safe, easy to perform and appears equally effective compared with intravenous infusion and (6) our strong recommendation is that alemtuzumab combination therapy and consolidation therapy shall not be used outside carefully controlled clinical studies

Subcutaneously Administered Ofatumumab in Rheumatoid Arthritis: A Phase I/II Study of Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics

“…The Journal of on May 10, 2018 -Published by www.jrheum.org Downloaded from at a lower dose and slower rate of absorption, leading to less rapid B cell depletion, may result in better tolerability and less need for premedication, as has been seen with another lymphocyte-depleting monoclonal antibody, alemtuzumab 12 .…”

Infections in Leukemia

“…Other infections include herpes simplex, varicella zoster, PJP, candidiasis, cryptococcosis, toxoplasmosis and mold infections(aspergillosis and mucormycosis) (17) It is recommended that all patients receiving alemtuzumab receive antiviral prophylaxis (acyclovir, valacyclovir or famciclovir). Although valganciclovir is effective in preventing CMV reactivation (146), it can suppress bone marrow function and current guidelines recommend weekly screening for CMV viremia using PCR, and pre-emptive treatment with ganciclovir or foscarnet when patients are symptomatic or show increase in viremia (144). In a Cancer and Leukemia Group (CALGB) study by Lin et al (147) alemtuzumab was administered to patients who received induction therapy with fludarabine and rituximab.…”

“…Given the near ubiquitous expression of CD52 on immune cells, treatment results in the loss of circulating T cells, leading to defective cell mediated immunity and neutropenia in approximately 1/3 of patients. As a result, CMV reactivation occurs in 15 to 25% of patients and is the most commonly observed opportunistic infection (137,(143)(144)(145). Other infections include herpes simplex, varicella zoster, PJP, candidiasis, cryptococcosis, toxoplasmosis and mold infections(aspergillosis and mucormycosis) (17) It is recommended that all patients receiving alemtuzumab receive antiviral prophylaxis (acyclovir, valacyclovir or famciclovir).…”

Chronic lymphocytic leukemia: treatment of relapse

“…Guidelines for the use of alemtuzumab include mandated weekly cytomegalovirus (CMV) PCR to check for the reactivation of CMV, cotrimoxazole prophylaxis to prevent Pneumocystis jirovecii pneumonia and acyclovir prophylaxis against herpes viruses. 9 If CMV infection is noted, preemptive therapy should be initiated with ganciclovir or foscarnet, and treatment with alemtuzumab should be interrupted. 9 Finally, the activity of novel targeted agents, although still in early stages of clinical investigation, has been promising and has shown potential to change the future treatment of CLL, for which allogeneic stem cell transplantation remains the only potentially curative therapy.…”

“…9 If CMV infection is noted, preemptive therapy should be initiated with ganciclovir or foscarnet, and treatment with alemtuzumab should be interrupted. 9 Finally, the activity of novel targeted agents, although still in early stages of clinical investigation, has been promising and has shown potential to change the future treatment of CLL, for which allogeneic stem cell transplantation remains the only potentially curative therapy. Continued advances in the research of CLL and enrollment of patients in clinical trials will aid in the pursuit of a future cure for CLL.…”