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Introducción: Se conoce que la incidencia de malignidad es significativamente mayor en los pacientes trasplantados que en la población general. La incidencia de enfermedad linfoproliferativa post trasplante (PTLD) es aproximadamente de 1% a 2% en los receptores de trasplante renal. El objetivo principal de este estudio fue evaluar la incidencia de PTLD en el seguimiento de pacientes trasplantados de riñón entre el 2005 y el 2010. Material y Métodos: Se tomaron de forma retrospectiva los datos de pacientes trasplantados de riñón entre los años 2005 a 2010 para determinar el número de casos de PTLD según el esquema inductor usado. Resultados: Se trasplantaron 425 pacientes en el periodo 2005 - 2010. Recibieron alemtuzumab 76.2%, daclizumab 10.7%, basiliximab 3.6% y timoglobulina 2.4%. No recibieron inducción con anticuerpos el 7 %. Durante este tiempo se presentaron 2 casos de

PTLD:

1 con mieloma múltiple y otro con linfoma. Uno de ellos recibió alemtuzumab y otro timoglobulina. Conclusiones: En esta cohorte de pacientes donde se usó predominantemente alemtuzumab, la incidencia de PTLD fue más baja que lo reportado en estudios previos.

The purpose of this study was to establish the efficacy and safety of two different doses of alemtuzumab (Lemtrada™) as a treatment for relapsing-remitting multiple sclerosis (MS), in comparison with subcutaneous interferon beta-1a (Rebif®). The study enrolled participants who had received an adequate trial of disease-modifying therapies but experienced at least 1 relapse during prior treatment, and who met a minimum severity of disease as measured by magnetic resonance imaging (MRI). Participants had monthly laboratory tests and comprehensive testing every 3 months.

RECORD STATUS:

This is a bibliographic record of a published health technology assessment from a member of INAHTA. No evaluation of the quality of this assessment has been made for the HTA database.

CITATION:

Catalan Agency for Health Information, Assessment and Quality (CAHIAQ -formerly CAHTA). Ofatumumab (Arzerra®) per al tractament de la leucèmia limfàtica crònica refractària a fludarabina i alemtuzumab. [Ofatumumab (Arzerra®) for the treatment of chronic lymphocytic leukaemia refractory to fludarabine and alemtuzumab] Barcelona: Catalan Agency for Health Information, Assessment and Quality (CAHIAQ -formerly CAHTA). CT07/2011. 2011

It has been shown that low-level preformed donor-specific antibodies (DSAbs) detected by luminex beads in the setting of a negative CDC and flow cytometry crossmatch (CDC/FCXM) are associated with inferior allograft outcomes. The relevance of preformed DSAbs in patients receiving alemtuzumab induction and tacrolimus monotherapy has not been studied. Four hundred and eighty renal transplant recipients with a negative CDC/FCXM had their pretransplant sera retrospectively screened for DSAbs. 45/480 (9.4%) of patients were found to have preformed DSAbs. Females and patients receiving regrafts were more likely to have a DSAb (p = 0.008 and p < 0.0001, respectively). Patients with DSAbs had inferior allograft survival (p = 0.047), increased incidence of antibody-mediated rejection (p < 0.0001) and inferior allograft function at 6 months posttransplant (p = 0.017). Patients with HLA class I DSAb (alone or in combination with a Class II DSAb) with high mean fluorescence intensities (MFIs) were at highest risk. We conclude that patients with preformed DSAb are at high risk of adverse outcomes when receiving a minimal immunosuppressive regime incorporating alemtuzumab induction. Patients found to have a preformed DSAb despite a negative crossmatch might benefit from augmented immunosuppression.

This study investigated the efficacy, safety, and clinical benefit of alemtuzumab (Campath-1H) for patients with relapsed or refractory B-cell chronic lymphocytic leukemia exposed to alkylating agents and having failed fludarabine therapy. Ninety-three patients received alemtuzumab in 21 centers worldwide, with the aim to obtain an overall response rate of at least 20%. Dosage was increased gradually (target 30 mg, 3 times weekly, for a maximum of 12 weeks). Infection prophylaxis was mandatory, beginning on day 8, and continuing for a minimum of 2 months after treatment. Responses were assessed at weeks 4, 8, and 12, and patients were followed for 34 months. Overall objective response in the intent-to-treat population (n = 93) was 33% (CR 2%, PR 31%). Median time to response was 1.5 months (range, 0.4-3.7 months). Median time to progression was 4.7 months overall, 9.5 months for responders. At data cut-off, 27 patients (29%) were alive; overall median survival was 16 months (95% CI.: 11.8-21.9) and 32 months for responders. Nineteen responders survived more than 21 months. Clinical benefit was observed both in responders and in patients with stable disease. The most common adverse events were related to infusion, generally grade 1 or 2 in severity, occurring mainly in the first week. Grade 3 or 4 infections were reported in 25 patients (26.9%). However, only 3 (9.7%) of 31 patients who responded to alemtuzumab treatment developed grade 3 or 4 infections on the study. Alemtuzumab induced significant responses in these patients with clinical benefit in the majority and with acceptable toxicity in a high-risk group.

Patients with relapsed chronic lymphocytic leukemia (CLL) and high-risk features, such as fludarabine refractoriness, complex karyotype, or abnormalities of chromosome 17p, experience poor outcomes after standard fludaradine-based regimens. Alemtuzumab is a chimeric CD52 monoclonal antibody with activity in CLL patients with fludarabine-refractory disease and 17p deletion. We report the outcome for 80 relapsed or refractory patients with CLL enrolled in a phase 2 study of cyclophosphamide, fludarabine, alemtuzumab, and rituximab (CFAR). All patients were assessed for response and progression according to the 1996 CLL-working group criteria. For the intention-to-treat analysis, the overall response rate was 65%, including 29% complete response. The estimated progression-free survival was 10.6 months and median overall survival was 16.7 months. Although we noted higher complete response in high-risk patients after CFAR compared with a similar population who had received fludarabine, cyclophosphamide, and rituximab as salvage therapy, there was no significant improvement in progression-free survival and overall survival appeared worse. CFAR was associated with a high rate of infectious complications with 37 patients (46%) experiencing a serious infection during therapy and 28% of evaluable patients experiencing late serious infections. Although CFAR produced good response rates in this highly pretreated high-risk group of patients, there was no benefit in survival outcomes.

RECORD STATUS:

This is a bibliographic record of a published health technology assessment from a member of INAHTA. No evaluation of the quality of this assessment has been made for the HTA database.

CITATION:

Hoyle M, Crathorne L, Garside R, Hyde C. Ofatumumab for the treatment of chronic lymphocytic leukaemia in patients who are refractory to fludarabine and alemtuzumab: a critique of the submission from GSK. Health Technology Assessment 2011; 15(Suppl 1 Article 7): 61-67

RECORD STATUS:

This is a bibliographic record of a published health technology assessment from a member of INAHTA. No evaluation of the quality of this assessment has been made for the HTA database.

CITATION:

NHSC. Alemtuzumab (MabCampath) for chronic lymphocytic leukaemia (first-line): horizon scanning technology ultra-orphan note Birmingham: National Horizon Scanning Centre (NHSC). 2006

On September 19, 2007, the U.S. Food and Drug Administration granted regular approval and expanded labeling for alemtuzumab (Campath); Genzyme Corporation, Cambridge, MA) as single-agent treatment for B-cell chronic lymphocytic leukemia (B-CLL). Alemtuzumab was initially approved in 2001 under accelerated approval regulations. Conversion to regular approval was based on a single study submitted to verify clinical benefit. Efficacy and safety were demonstrated in an open-label, international, multicenter, randomized trial of 297 patients with previously untreated, Rai stage I-IV B-CLL experiencing progression of their disease. Patients were randomized to either alemtuzumab, 30 mg i.v. over 2 hours three times per week on alternate days for a maximum of 12 weeks, or chlorambucil, 40 mg/m(2) orally every 28 days for a maximum of 12 months. The progression-free survival time, the primary study endpoint, was significantly longer in the alemtuzumab arm than in the chlorambucil arm. Both the overall and complete response rates were also significantly higher in the alemtuzumab arm. No differences in survival were observed. There were no new safety signals identified in patients receiving alemtuzumab. The most serious, and sometimes fatal, toxicities of alemtuzumab are cytopenias, infusion reactions, and infections.