RESUMO
Myeloproliferative neoplasms (MPNs) are a group of chronic hematologic malignancies that lead to morbidity and early mortality due to thrombotic complications and progression to acute leukemia. Clinical and mutational risk factors have been demonstrated to predict outcomes in patients with MPNs and are used commonly to guide therapeutic decisions, including allogenic stem cell transplant, in myelofibrosis. Adolescents and young adults (AYA, age ≤45 years) comprise less than 10% of all MPN patients and have unique clinical and therapeutic considerations. The prevalence and clinical impact of somatic mutations implicated in myeloid disease has not been extensively examined in this population. We conducted a retrospective review of patients evaluated at eight Canadian centers for MPN patients diagnosed at ≤45 years of age. In total, 609 patients were included in the study, with median overall survival of 36.8 years. Diagnosis of prefibrotic or overt PMF is associated with the lowest OS and highest risk of AP/BP transformation. Thrombotic complications (24%), including splanchnic circulation thrombosis (9%), were frequent in the cohort. Mutations in addition to those in JAK2/MPL/CALR are uncommon in the initial disease phase in our AYA population (12%); but our data indicate they may be predictive of transformation to post-ET/PV myelofibrosis.
Assuntos
Transtornos Mieloproliferativos , Policitemia Vera , Mielofibrose Primária , Trombocitemia Essencial , Trombose , Humanos , Adulto Jovem , Adolescente , Pessoa de Meia-Idade , Mielofibrose Primária/genética , Mielofibrose Primária/terapia , Policitemia Vera/genética , Trombocitemia Essencial/genética , Canadá/epidemiologia , Transtornos Mieloproliferativos/complicações , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/terapia , Trombose/genética , Janus Quinase 2/genética , Mutação , Calreticulina/genéticaRESUMO
New therapies in a publicly funded healthcare system are first appraised by health technology assessment agencies that provide funding recommendations to the payers. Treatment with Chimeric Antigen Receptor-T cell (CAR-T) therapy is revolutionizing the management of patients with relapsed/refractory aggressive B-cell lymphoma by providing an effective alternative to the standard of care. Yet, the implementation of CAR-T treatment has a substantial impact on the healthcare system due to its high cost, complex manufacturing process, and requirement for highly specialized services and expertise. CAR-T Cells, as a "living drug", are fundamentally different from usual medications, and their approvals and funding recommendations pose unique challenges to the health technology agency. In this paper, we explore the specific challenges that face the health technology agencies in reviewing reimbursement recommendations for CAR-T therapy. We take a Canadian perspective and use CAR-T treatment of relapse/refractory aggressive B-cell lymphoma as an example.
Assuntos
Linfoma de Células B , Receptores de Antígenos Quiméricos , Humanos , Receptores de Antígenos Quiméricos/uso terapêutico , Recidiva Local de Neoplasia , Canadá , Linfoma de Células B/terapia , Linfócitos TAssuntos
Transplante de Células-Tronco Hematopoéticas , Células Precursoras de Linfócitos T , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Anticorpos Monoclonais , Arabinonucleosídeos , Humanos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Terapia de SalvaçãoRESUMO
BACKGROUND: Azacitidine is an hypomethylating agent widely adopted for the treatment of acute myeloid leukaemia (AML) in patients who are ineligible for curative-intent chemotherapy. Patients with low bone marrow blast counts (< 30%) experience improved survival with azacitidine, but the benefits are significantly lower in patients with > 30% blasts in the bone marrow. As such, there is uncertainty around the economic benefit of azacitidine in patients with higher blast counts. OBJECTIVE: We present a cost-utility analysis of azacitidine in patients with AML with > 30% blasts to determine the economic value of azacitidine in this patient population from the perspective of a third-party payer. METHODS: A Markov model was developed with a time horizon of 25 months divided into 22 cycles of 35 days each. The cost utility of azacitidine was compared with that of conventional care regimens (which include best supportive care, low-dose cytarabine and induction chemotherapy). A Canadian public healthcare system perspective was selected. RESULTS: In the base case, the incremental cost per quality-adjusted life-year gained (incremental cost-effectiveness ratio [ICER]) for azacitidine compared with conventional care regimens was $Can160,438, year 2018 values. The estimated ICER was insensitive to a longer time horizon but sensitive to the cost of azacitidine and to assumptions relating to survival in both treatment regimens, although the ICER always remained greater than Can$80,000 in all scenarios. CONCLUSION: Azacitidine is unlikely to be cost effective given that the estimated ICER exceeds the willingness to pay commonly used in the Canadian healthcare system.