Brentuximab Vedotin for Hodgkin´s Lymphoma

PICHON RIVIERE, A.; AUGUSTOVSKI, F.; GARCIA MARTI, S.; ALCARAZ, A.; GLUJOVSKY, D.; LOPEZ, A.; REY-ARES, L.; BARDACH, A.; CIAPONI, A; URTASUN, M; SOTO, N

Documento de Evaluación de Tecnologías Sanitarias

IECS

Año: 2013 p. 1 - 30

1668-2793

Hodgkin?s lymphoma (HL) is a monoclonal neoplasm originating in the B lymphocytes. Its incidence is less than 1/100,000 cases-year in developing countries. Prognosis varies depending on the stage at diagnosis and, with appropriate treatment, overall survival at 5 years is 80-90%. The World Health Organization (WHO) divides it in 2 types, classical HL (CLH), accounting for 95% of the cases, and nodular lymphocyte predominant Hodgkin´s lymphoma (NLPHL). CHL treatment may start with chemotherapy plus radiotherapy or chemotherapy alone using three main regimens (ABVD, Stanford V and BEACOPP) which combine doxorubicin, bleomycin, vinblastine, etoposide, prednisone, vincristine, cyclophosphamide, procarbazine and dacarabazine. Five to ten percent of the patients will show resistance to this first line and 10-30% of respondents will relapse. In case of resistance or relapse, a second line chemotherapy regimen is administered. No regimen has shown superiority, therefore it is chosen based on medical judgment. The following schemes are usually used: ICE, GDP, BEAM and DHAP. These are combinations of dexamethasone, cytarabine, cisplatin, etoposide, gemcitabine, carboplatin, carmustine, iphosphamide and/or melphalan. In general, they are indicated as preparation for high dose chemotherapy with autologous stem cell transplant (HDT/ASCR) which, although it has not demonstrated to increase overall survival, has shown longer disease-free survival and event-free survival. Overall survival at 5 years in patients who received autologous transplant is 43%. If there is a new relapse, there are few options and median survival is approximately 26 months.In view of the poor response and high toxicity of the available treatments, treatments based on monoclonal antibodies become a potentially useful alternative for patients with refractory or relapsing HL.TechnologyBrentuximab vedotin is a monoclonal antibody bound to a cytotoxic drug and targeted against the CD30 receptor, then it can only be used in CD30 positive neoplasms. It is administered at 1.8 mg/kg single intravenous infusion cycles, 3 weeks apart, for up to 16 cycles.PurposeTo assess the available evidence on the efficacy, safety and coverage policy related issues on the use of brentuximab vedotin in patients with Hodgkin´s Lymphoma.MethodsA bibliographic search was carried out on the main databases: DARE, NHS EED, on Internet general search engines, in health technology evaluation agencies and health sponsors. Priority was given to the inclusion of systematic reviews (SRs); controlled, randomized clinical trials (RCTs); health technology assessments (HTAs) and economic evaluations; clinical practice guidelines and coverage policies of other health systems.ResultsNo RCTs or SRs were identified. One HTA was included and updated in this report; no additional studies not already included in this HTA were identified. Six coverage policies were identified.In 2013, one HTA expedited report identified six case series of CHL patients. Five of them reported objective response (OR) rates in 50% to 75% of the patients and in all of them complete response (CR) was observed in 17% to 34% of the patients. When reported, the response duration was 8 to 10 months and progression free survival ranged from 5.1 to 7.8 months. Brentuximab was considered moderately toxic. The most common adverse effects were: peripheral neuropathy, tiredness, nausea, diarrhea, arthralgia, pyrexia, cough, dyspnea and neutropenia.One of the series included in this report highlights the importance of its size, assessing 102 patients with refractory or relapsing HL already treated with HDT/ASCR. Thirty percent were alive and disease progression free after a median follow up of 18.5 (range 1.8 to 23.5); 28 deaths were reported and overall survival at 12 months was 89% (95%CI 83%-95%). Reports informed after this study suggest a 65% overall survival at 2 years, while overall survival at 2 years achieved with standard treatment is between 48% and 65%.A consensus of U.S. experts recommends the use of brentuximab as a therapeutic alternative for patients who failed HDT/ASCR or at least two prior chemotherapy regimens, regardless of their HDT/ASCR.The identified health sponsors, all of them from the U.S., agree to cover brentuximab in patients with resistant disease after HDT/ASCR or after at least two treatment lines in patients who are not eligible for autologous transplant.ConclusionsThe quality of the available evidence to date is very poor and is based on case series reporting interim result measurements and short term follow-up. However, the efficacy data and toxicity profile suggest brentuximab vedotin might be a therapeutic alternative for resistant or relapsing HL patients failing in at least two lines of treatment and in whom HDT/ASCR is contraindicated, or if HDT/ASCR fails.