Limited information is available on alemtuzumab in the nonclinical trial setting. We evaluated its efficacy and safety in 42 consecutive unselected patients who received alemtuzumab monotherapy in British Columbia between October 2002 and August 2006. Information on patient demographics, baseline clinical characteristics, dose and schedule, clinical response, survival, and toxicities associated with alemtuzumab was collected retrospectively. Thirty-nine of 42 patients had chronic lymphocytic leukemia, two had mycosis fungoides, and one had T-cell post-transplant lymphoproliferative disorder. In contrast to previous reports, 42% were treated by community practitioners and 83% received alemtuzumab subcutaneously. The median time from diagnosis to alemtuzumab was 58 months. One of 42 patients (2%) achieved a complete response, 20 (48%) achieved a partial response, and 13 (31%) had stable disease. The post-alemtuzumab median overall survival was 15.1 months. Response to alemtuzumab correlated with an increased progression-free survival (11 vs. 3.6 months, p = 0.001) compared to that seen in non-responders. Significant adverse events included grade 3/4 neutropenia (76%), thrombocytopenia (45%), infections (60%) and death (12%). With careful monitoring, alemtuzumab can be safely administered in a wide variety of clinical settings, including community practice, and is associated with a high level of activity in situations with few available alternative treatment options.

RECORD STATUS:

This is a bibliographic record of an ongoing health technology assessment being undertaken by a member of INAHTA. Links to the published report and any other relevant documentation will be added when available.

CITATION:

Alemtuzumab for the treatment of relapsing-remitting multiple sclerosis. Health Technology Assessment

RECORD STATUS:

None

CITATION:

Canadian Coordinating Office for Health Technology Assessment. Alemtuzumab for the treatment of B cell chronic lymphocytic leukemia. Ottawa: Canadian Coordinating Office for Health Technology Assessment (CCOHTA) 2004

Objective: The objective of this study was to compare efficacy and safety of alemtuzumab, antithymocyte globulin (ATG), and daclizumab for induction therapy in organ transplantation. Methods: We searched PUBMED, EMBASE, and Cochrane databases to identify randomized controlled trials that compared alemtzumab, ATG, and daclizumab for induction therapy in kidney as well as pancreas transplantation. According to the inclusion criteria, the collected data included general characteristics of the studies and their major outcomes. The meta-analysis was performed using RevMan 5.0.25 software. Results: We identified 9 studies involving 777 patients. No differences between alemtuzumab, daclizumab, and ATG were observed in terms of patient survival, graft survival, or acute rejection episodes at a 24-month follow-up (P =.62, P =.55, and P =.08, respectively). Infections within 36 months were greater between the alemtuzumab and the ATG group (P =.03). There was no significant difference in terms of infection at 24 months. Conclusions: Alemtuzumab and daclizumab appeared to be as effective as ATG for induction therapy in kidney transplantation at a follow-up of 24 months. However, alemtuzumab showed a lower rate of infection at 36 months compared with ATG. © 2012 Elsevier Inc.

We explored the safety and efficacy of rituximab plus alemtuzumab in patients with relapsed or refractory lymphoid malignancies. Forty-eight patients were treated and were assessable for response (32 with chronic lymphocytic leukemia [CLL], 9 with CLL/prolymphocytic leukemia [PLL], 1 with PLL, 4 with mantle cell leukemia/lymphoma, 2 with Richter transformation). The overall response rate was 52% (complete remission, 8%; nodular partial response, 4%; partial response, 40%). With a median follow-up of 6.5 months (range, 1-20 months), the median time to progression was 6 months (range, 1-20 months); median survival, 11 months (11+ months for responders vs 6 months for nonresponders). Most toxicities were grade 2 or lower and infusion-related. Infections occurred in 52% of the patients. Cytomegalovirus (CMV) antigenemia assays were positive in 27% of the patients, but only 15% were symptomatic and required therapy. The combination of rituximab and alemtuzumab is feasible, has an acceptable safety profile, and has clinical activity with a short course in a group of patients with poor prognoses.

BACKGROUND:

Alemtuzumab, a humanized monoclonal antibody that targets CD52 on lymphocytes and monocytes, may be an effective treatment for early multiple sclerosis.

METHODS:

In this phase 2, randomized, blinded trial involving previously untreated, early, relapsing-remitting multiple sclerosis, we assigned 334 patients with scores of 3.0 or less on the Expanded Disability Status Scale and a disease duration of 3 years or less to receive either subcutaneous interferon beta-1a (at a dose of 44 microg) three times per week or annual intravenous cycles of alemtuzumab (at a dose of either 12 mg or 24 mg per day) for 36 months. In September 2005, alemtuzumab therapy was suspended after immune thrombocytopenic purpura developed in three patients, one of whom died. Treatment with interferon beta-1a continued throughout the study.

RESULTS:

Alemtuzumab significantly reduced the rate of sustained accumulation of disability, as compared with interferon beta-1a (9.0% vs. 26.2%; hazard ratio, 0.29; 95% confidence interval [CI], 0.16 to 0.54; P<0.001) and the annualized rate of relapse (0.10 vs. 0.36; hazard ratio, 0.26; 95% CI, 0.16 to 0.41; P<0.001). The mean disability score on a 10-point scale improved by 0.39 point in the alemtuzumab group and worsened by 0.38 point in the interferon beta-1a group (P<0.001). In the alemtuzumab group, the lesion burden (as seen on T(2)-weighted magnetic resonance imaging) was reduced, as compared with that in the interferon beta-1a group (P=0.005). From month 12 to month 36, brain volume (as seen on T(1)-weighted magnetic resonance imaging) increased in the alemtuzumab group but decreased in the interferon beta-1a group (P=0.02). Adverse events in the alemtuzumab group, as compared with the interferon beta-1a group, included autoimmunity (thyroid disorders [23% vs. 3%] and immune thrombocytopenic purpura [3% vs. 1%]) and infections (66% vs. 47%). There were no significant differences in outcomes between the 12-mg dose and the 24-mg dose of alemtuzumab.

CONCLUSIONS:

In patients with early, relapsing-remitting multiple sclerosis, alemtuzumab was more effective than interferon beta-1a but was associated with autoimmunity, most seriously manifesting as immune thrombocytopenic purpura. The study was not powered to identify uncommon adverse events. (ClinicalTrials.gov number, NCT00050778.)

CRD SUMMARY:

The review concluded that alemtuzumab induction was superior to traditional antibodies in preventing acute rejection in renal transplantation, but this benefit may not extend to high immunological risk patients. The review results were based on small trials and the trial quality assessment results were not used to inform the review conclusions; these factors limit the reliability of the authors' conclusions.

RECORD STATUS:

None

CITATION:

National Institute for Health and Clinical Excellence. Ofatumumab for the treatment of chronic lymphocytic leukaemia refractory to fludarabine and alemtuzumab. London: National Institute for Health and Clinical Excellence (NICE). Technology Appraisal Guidance 202. 2010

The purpose of this study was to establish the efficacy and safety of alemtuzumab (Lemtrada™) as a treatment for relapsing-remitting multiple sclerosis (MS), in comparison with subcutaneous (SC) interferon beta-1a (Rebif®). The study had enrolled participants who had not previously received MS disease-modifying therapies. Participants had monthly laboratory tests and comprehensive testing every 3 months.

Purpose: We conducted a randomized trial to evaluate the efficacy and safety of intravenous alemtuzumab compared with chlorambucil in first-line treatment of chronic lymphocytic leukemia (CLL). Patients and Methods: Patients received alemtuzumab (30 mg three times per week, for up to 12 weeks) or chlorambucil (40 mg/m2 every 28 days, for up to 12 months). The primary end point was progression-free survival (PFS). Secondary end points included overall response rate (ORR), complete response (CR), time to alternative therapy, safety, and overall survival. Results: We randomly assigned 297 patients, 149 to alemtuzumab and 148 to chlorambucil. Alemtuzumab had superior PFS, with a 42% reduction in risk of progression or death (hazard ratio [HR] = 0.58; P = .0001), and a median time to alternative treatment of 23.3 versus 14.7 months for chlorambucil (HR = 0.54; P = .0001). The ORR was 83% with alemtuzumab (24% CR) versus 55% with chlorambucil (2% CR); differences in ORR and CR were highly statistically significant (P < .0001). Elimination of minimal residual disease occurred in 11 of 36 complete responders to alemtuzumab versus none to chlorambucil. Adverse events profiles were similar, except for more infusion-related and cytomegalovirus (CMV) events with alemtuzumab and more nausea and vomiting with chlorambucil. CMV events had no apparent impact on efficacy. Conclusion: As first-line treatment for patients with CLL, alemtuzumab demonstrated significantly improved PFS, time to alternative treatment, ORR and CR, and minimal residual disease-negative remissions compared with chlorambucil, with predictable and manageable toxicity. © 2007 by American Society of Clinical Oncology.