RESUMEN
Understanding the global epidemiology of AML is critical for assessing therapeutic demand and informing healthcare resource allocation. This study estimated current and future AML incidence in 27 countries, described AML survival trends in the United States, and calculated average years of life lost (AYLL). Incidence rates were age-standardized using rates from IARC's Cancer Incidence in Five Continents and SEER databases and ranged from 0.70 to 3.23 cases per 100,000 persons. Crude incidence rates were projected from 2024 to 2040; growth varied from +1% to +46%. Median overall survival was derived from SEER databases and increased from 4 to 11 months over the last 40 years. Median AYLL of 18.6 years was estimated for 27 countries. This study projected significant growth in new AML diagnoses over the next two decades. Despite improvements in survival over the last four decades, median survival among AML patients remains poor highlighting the need for novel treatments.
RESUMEN
Blinatumomab has demonstrated significant efficacy in adult and pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-cell ALL) and patients with measurable residual disease (MRD). This review aimed to compare median relapse-free survival (RFS) and median overall survival (OS) in adult and pediatric patients with R/R or MRD-positive B-cell ALL from pivotal studies [MT-103-211 and TOWER for adults with Philadelphia chromosome (Ph)-negative R/R B-cell ALL, ALCANTARA for adults with Ph-positive R/R B-cell ALL, MT-103-203 for adults with MRD-positive B-cell ALL, and MT-103-205 for pediatric patients with R/R B-cell ALL], with the median RFS and OS from retrospective analyses, country or ethnicity-specific studies, and studies based on real-world evidence (RWE) identified from a literature search. Adults with Ph-negative R/R B-cell ALL who received blinatumomab as first salvage demonstrated a numerically longer median OS compared with that in patients from pivotal studies (MT-103-211 and TOWER) without additional safety concerns. In pediatric patients with R/R B-cell ALL treated with blinatumomab, the median RFS and OS from retrospective analyses and country/ethnicity-specific studies were comparable with the median RFS and OS from the pivotal study MT-103-205. The median RFS and OS from RWE studies in adults with R/R B-cell ALL were numerically longer than the median RFS and OS from pivotal studies (MT-103-211, TOWER, and ALCANTARA); however, this trend was not observed in pediatric patients with R/R B-cell ALL. In conclusion, this analysis identified first salvage adults with Ph-negative R/R B-cell ALL as particularly well-suited for treatment with blinatumomab since survival outcomes from retrospective analyses reported in this patient subgroup were numerically better compared with those from pivotal studies without additional safety signals.
Asunto(s)
Anticuerpos Biespecíficos , Antineoplásicos , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Adulto , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Anticuerpos Biespecíficos/efectos adversos , Recurrencia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamiento farmacológico , Antineoplásicos/efectos adversos , Antígenos CD19/uso terapéuticoAsunto(s)
Anticuerpos Biespecíficos/uso terapéutico , Antineoplásicos/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adulto , Anticuerpos Biespecíficos/efectos adversos , Antineoplásicos/efectos adversos , Humanos , Recurrencia Local de Neoplasia/genética , Cromosoma Filadelfia/efectos de los fármacos , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Resultado del TratamientoRESUMEN
The B cell surface antigen CD19 is a target for treating B cell malignancies, such as B cell precursor acute lymphoblastic leukemia and B cell non-Hodgkin lymphoma. The BiTE® immuno-oncology platform includes blinatumomab, which is approved for relapsed/refractory B cell precursor acute lymphoblastic leukemia and B cell precursor acute lymphoblastic leukemia with minimal residual disease. Blinatumomab is also being evaluated in combination with other agents (tyrosine kinase inhibitors, checkpoint inhibitors, and chemotherapy) in various treatment settings, including frontline protocols. An extended half-life BiTE molecule is also under investigation. Patients receiving blinatumomab may experience cytokine release syndrome and neurotoxicity; however, these events may be less frequent and severe than in patients receiving other CD19-targeted immunotherapies, such as chimeric antigen receptor T cell therapy. We review BiTE technology for treating malignancies that express CD19, analyzing the benefits and limitations of this bispecific T cell engager platform from clinical experience with blinatumomab.
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Anticuerpos Biespecíficos/uso terapéutico , Antígenos CD19/inmunología , Antígenos de Neoplasias/inmunología , Antineoplásicos Inmunológicos/uso terapéutico , Subgrupos de Linfocitos B/inmunología , Linfoma de Células B/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Adolescente , Corticoesteroides/uso terapéutico , Adulto , Anticuerpos Biespecíficos/administración & dosificación , Anticuerpos Biespecíficos/efectos adversos , Anticuerpos Biespecíficos/economía , Antineoplásicos Inmunológicos/administración & dosificación , Antineoplásicos Inmunológicos/efectos adversos , Antineoplásicos Inmunológicos/economía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Ensayos Clínicos como Asunto , Terapia Combinada , Análisis Costo-Beneficio , Síndrome de Liberación de Citoquinas/etiología , Síndrome de Liberación de Citoquinas/prevención & control , Costos de los Medicamentos , Humanos , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/economía , Infusiones Intravenosas , Inyecciones Subcutáneas , Linfoma de Células B/tratamiento farmacológico , Linfoma de Células B/inmunología , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patología , Premedicación , Calidad de Vida , Subgrupos de Linfocitos T/inmunología , Resultado del Tratamiento , Carga Tumoral , Escape del TumorRESUMEN
This systematic literature review compared clinical outcomes post-stem cell transplantation (SCT) among patients with vs. without the measurable residual disease (MRD) pre-transplant. Relevant literature on adults undergoing transplant with known MRD status pre-transplant was extracted from the MEDLINE, Embase, and CENTRAL databases (through 8 May 2018) and oncology conferences (2014-2018) using keywords for acute lymphoblastic leukemia and MRD. Thirty primary studies reporting SCT outcomes were identified. Hazard ratios (HRs) for overall survival indicated that patients with MRD pre-transplant were more likely to die post-SCT vs. patients with no detectable MRD (HR: 1.51-3.856). In post-SCT relapse studies, 16-100% of patients with MRD vs. 0-50% of patients without MRD relapsed. This review found evidence of markedly worse outcomes post-transplant among patients with vs. without MRD pre-transplant, including shorter median survival (overall, relapse-free, and event-free survival), higher risk of death, more relapse events, and decreased likelihood of remaining in hematologic remission.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Trasplante de Células Madre , Trasplante HomólogoRESUMEN
Multiple myeloma is a malignancy of B cells characterized by accumulation of abnormal plasma cells in the bone marrow. In the past 20 years, the use of high-dose therapies and novel agents has resulted in significant and meaningful improvements in survival. Autologous stem cell transplantation (auto-SCT) following a high-dose melphalan-conditioning regimen represents the standard of care for younger patients as well as older patients with a good performance status. A number of strategies have been proposed to improve the outcome of auto-SCTs, including the incorporation of new agents such as thalidomide, lenalidomide, and bortezomib into the induction regimen administered before auto-SCT; the administration of maintenance therapy after auto-SCT; the incorporation of novel agents into chemotherapeutic regimens after transplantation as consolidation therapy; and the use of reduced-intensity allogeneic transplantation after an initial autograft. Although these approaches have demonstrated some success in improving responses after auto-SCT, none of these strategies are curative. An additional strategy to improve outcomes after auto-SCT is to enhance the immediate pretransplant conditioning regimens by either increasing the dose of melphalan or by incorporating novel agents, such as busulfan. This literature review focuses on the efficacy and safety of busulfan-based conditioning regimens for auto-SCT in patients with multiple myeloma.