RESUMO
Nivolumab is a treatment option for patients with metastatic renal cell carcinoma (RCC) previously treated with targeted antiangiogenic therapy. Papillary renal cell carcinoma (PRCC) comprises 10-15% of RCC cases but non-clear cell subtypes were excluded from the immunotherapy trials. We report the case of a woman with recurrent metastatic PRCC who had an impressive therapeutic response to nivolumab with no significant adverse events. She had previously been treated with sunitinib and pazopanib with no response. She showed a remarkable clinical improvement after only the first 2 immunotherapy cycles and subsequent radiographic studies demonstrated a marked decrease in tumor burden. At present, she continues to show a durable benefit after 8 months of treatment. Her tumor had <1% positivity for PD-L1 staining and a low tumor mutational burden with no actionable mutations on genomic sequencing. Considering its high genetic variation, checkpoint blockade immunotherapies (CBIs) are attractive treatment options in PRCC. This is the third case that reports objective responses of nivolumab in PRCC. We believe our patient's experience supports the inclusion of non-clear cell RCC on clinical trials using CBIs. PD-L1 status and TMB may not serve as predictive biomarkers for response.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Adulto , Feminino , Humanos , Imunoterapia/métodos , NivolumabeRESUMO
BACKGROUND: Cytopenia is associated with cancer through mechanisms including clonal hematopoiesis and chronic inflammation. Cytopenia is more prevalent in Black people but its relationship with racial disparities in cancer mortality is unknown. METHODS: Cytopenia was defined in 19,028 Black and White participants recruited between 2003 and 2007 for the REasons for Geographic and Racial Differences in Stroke cohort, based on age-, sex-, and race-adjusted ranges for blood counts. Cancer death was ascertained from Social Security Death and National Death Indexes. Multivariable Cox models estimated the risk of cancer mortality associated with cytopenia, adjusting for demographics (model1), anemia and cancer risk factors (model2), and socioeconomics (model3). Racial differences in the cytopenia-cancer death association were tested by cross-product interaction terms. RESULTS: Cytopenia was identified in 383 (2%) participants, 250 (65%) White, and 113 (35%) Black people. With median follow-up 11.3 years, 1,224 (6.4%) cancer deaths occurred. Cytopenia was associated with increased risk of cancer mortality in model1 (HR = 1.57, 95%CI 1.15-2.24), model2 (HR = 1.67, 95%CI 1.22-2.30), and model3 (HR = 1.59, 95%CI 1.17-2.17). Participants with cytopenia had twofold increased cumulative incidence of cancer death (13% vs. 6.5%, p < 0.01). Race by cytopenia interaction terms showed higher HR for cancer death in Black compared to White participants: 2.01 versus 1.41 (pinteraction = 0.016, model1), 2.12 versus 1.45 (pinteraction = 0.009, model2), and 1.82 versus 1.44 (pinteraction = 0.04, model3). CONCLUSION: In this large, observational biracial prospective study, cytopenia was a risk factor for cancer death, with stronger association in Black than White people. Though race impacted the association of cytopenia with cancer mortality, cytopenia was not a mediator of the racial disparity in cancer mortality.
Assuntos
Anemia , Neoplasias , Humanos , Estados Unidos , Estudos Prospectivos , Fatores Raciais , Fatores de Risco , BrancosRESUMO
A sizable proportion of patients with acute myeloid leukemia (AML) fail to achieve remission. Hematopoietic stem cell transplantation (HSCT) is the only intervention with potential of long-term survival. A recent Acute Leukemia Working Party (ALWP)/European Society for Blood and Marrow Transplantation (EBMT) analysis reports substantial posttransplant survival gains for patients with active disease who received transplants. Decreased relapse was the largest contributor to survival, a cause for optimism in this challenging population. See related article by Nagler et al., p. 4258.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Doença Aguda , Humanos , Leucemia Mieloide Aguda/mortalidade , Recidiva , Estudos RetrospectivosRESUMO
Alternative statistical designs cannot fully mitigate the limitations of traditional clinical trials in rare cancers. Creative study designs that integrate early clinical data and correlative outcomes from concomitant translational and laboratory models to evaluate the efficacy of druggable targets can potentially expedite access to novel therapies for these patients.See related article by Hunter et al., p. 6095.