RESUMEN
Asynchronous learning continues to gain popularity in medical education. One medium to facilitate asynchronous learning is the podcast. Currently, there are a limited number of hematology/oncology (H/O) podcasts geared towards residents and fellows ("trainees"). To address this need, we created a series of podcasts covering fundamental H/O topics for H/O fellows and internal medicine residents rotating on H/O services. We evaluate the effectiveness of this approach in this pilot study. Between September 2022 and February 2023, residents received recommended episodes via email prior to their rotation. Following their rotation, they received a survey. H/O fellows were encouraged to listen to any available episodes during the study period, after which they also received a survey. The survey collected baseline user information and included a 5-point Likert scale to determine if the podcast episodes were effective educational tools. Summary description was performed by the authors. In total 7 internal medicine residents (27 eligible) and 13 H/O fellows (18 eligible) completed the survey, for a total group of 20 respondents. The trainees found that the podcast helped with inpatient and outpatient management, was clinically relevant, and helped with clinical decision-making. They also agreed that the fundamentals of H/O are amenable to the podcast platform and are likely to continue to use podcasts as learning tools in H/O. This pilot study suggests that podcasts are an effective supplemental learning tool for the fundamentals of H/O in graduate medical education. The use of podcasts as educational tools should be encouraged for trainees.
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Educación Médica , Hematología , Humanos , Proyectos Piloto , Educación de Postgrado en Medicina , Oncología Médica , Encuestas y CuestionariosRESUMEN
PURPOSE OF REVIEW: Multiple myeloma is a common hematologic malignancy characterized by recurrent relapsing disease course requiring use of various therapies. Over the past few decades, significant advancements in the treatment of myeloma have occurred including routine use of proteasome inhibitors and immunomodulatory drugs. These have effectively improved survival; however, some also have increased risk of cardiovascular toxicity. Here, we will review the incidence, pathophysiology, and management of cardiovascular complications associated with antimyeloma agents. RECENT FINDINGS: Cardiovascular complications associated with myeloma treatment are common. These cardiovascular complications include accelerated hypertension, ischemic heart disease, congestive heart failure, arrhythmia, pulmonary hypertension, venous thromboembolism, and arterial thromboembolism. Thromboprophylactic strategies during treatment with immunomodulatory agents and screening strategies to detect changes in myocardial function prior to the development of overt heart failure have occurred. Cardiovascular complications associated with proteasome inhibitors and immunomodulatory drugs are an important component in supportive care of patients with myeloma. The incidence of cardiotoxicity is high, and, as such, early intervention and collaborative efforts between cardiologists and oncologists to mitigate and effectively manage these complications are imperative. Additional studies are needed to clarify the underlying pathophysiology and evaluate effective strategies for prevention and treatment.
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Antineoplásicos/efectos adversos , Cardiotoxicidad/prevención & control , Cardiopatías/prevención & control , Factores Inmunológicos/efectos adversos , Mieloma Múltiple/tratamiento farmacológico , Inhibidores de Proteasoma/efectos adversos , Cardiotoxicidad/epidemiología , Cardiotoxicidad/etiología , Cardiotoxicidad/fisiopatología , Manejo de la Enfermedad , Cardiopatías/inducido químicamente , Cardiopatías/epidemiología , Cardiopatías/fisiopatología , Humanos , Incidencia , Mieloma Múltiple/patología , Estados Unidos/epidemiologíaRESUMEN
PURPOSE: Axicabtagene ciloleucel (axi-cel) is an autologous CD19 chimeric antigen receptor (CAR) T-cell therapy that is approved for the treatment of relapsed or refractory large B-cell lymphoma. Little is known about the long-term survivorship after CAR T-cell therapy. METHODS: We previously reported the results of 298 patients who were leukapheresed with the intent to receive standard-of-care axi-cel (n = 275 infused) after two or more previous lines of therapy at a median follow-up of 12.9 months. Here, we report extended follow-up of this cohort to a median of 58 months, with a focus on late survivorship events. RESULTS: Among axi-cel-infused patients, progression-free survival at 5 years was 29% and overall survival (OS) at 5 years was 40%. The 5-year lymphoma-specific survival was 53% with infrequent late relapses. However, the 5-year nonrelapse mortality (NRM) was 16.2%, with over half of NRM events occurring beyond 2 years. Patients who were 60 years and older had a lower risk of relapse (P = .02), but a higher risk of NRM compared with patients younger than 60 years (NRM odds ratio, 4.5 [95% CI, 2.1 to 10.8]; P < .001). Late NRM was mainly due to infections and subsequent malignant neoplasms (SMNs). In total, SMNs occurred in 24 patients (9%), including therapy-related myeloid neoplasms (n = 15), solid tumors (n = 7), and unrelated lymphoid malignancies (n = 2). CONCLUSION: In the standard-of-care setting, axi-cel exhibits outcomes consistent with those reported in clinical trials, with sustained, durable responses observed at the 5-year time point. However, late infections and the development of SMN are key survivorship issues that reduce long-term survival after CAR T-cell therapy, particularly in the elderly.
RESUMEN
Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of many patients with aggressive relapsed or refractory large B-cell lymphoma (LBCL). Treatment can be complicated by clinically evident cytokine release syndrome (CRS), which is characterized by the development of fever, hypoxia, and hypotension, and can be life-threatening. Most patients treated with CAR-T cells develop CRS, which is thought to represent an immune phenomenon. It was previously unknown whether patients who did not develop CRS had reduced CAR-T cell activity and were therefore likely to have worse outcomes. We conducted a multicenter retrospective analysis of 352 adult patients treated at 8 academic medical centers in the United States who received axicabtagene ciloleucel or tisagenlecleucel for the treatment of LBCL. The outcomes of interest included progression-free survival, overall survival, complete response rate, and overall response rate. Of the included patients, 262 (74.4%) developed CRS. There was no significant difference in progression-free survival (P = .99) or overall survival (P = .16) between patients who developed CRS and those who did not develop CRS. Peak ferritin levels >5000 ng/mL during treatment and lactate dehydrogenase levels greater than the institutional upper limit of normal before lymphodepleting chemotherapy were associated with significantly worse progression-free and overall survival in the multivariate analysis. There was no significant difference in the complete response or overall response rates between patients who did and did not develop CRS. In this retrospective analysis, we report that patients who develop CRS have clinical outcomes similar to those of patients without CRS treated with commercial anti-CD19 CAR-T cells.
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Linfoma de Células B Grandes Difuso , Receptores Quiméricos de Antígenos , Adulto , Humanos , Estados Unidos , Receptores Quiméricos de Antígenos/uso terapéutico , Síndrome de Liberación de Citoquinas/etiología , Síndrome de Liberación de Citoquinas/terapia , Estudios Retrospectivos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Antígenos CD19 , Tratamiento Basado en Trasplante de Células y TejidosRESUMEN
Tisagenlecleucel (tisa-cel) is an approved CD19-directed chimeric antigen receptor T cell (CAR-T) therapy for relapsed/refractory B cell malignancies. Given potentially life-threatening toxicities, including cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, inpatient tisa-cel infusion and toxicity monitoring are often considered; however, the toxicity profile of tisa-cel may be conducive to outpatient administration. Here we review the characteristics and outcomes of tisa-cel recipients treated in the outpatient setting. Patients age ≥18 years with B cell non-Hodgkin lymphoma who received tisa-cel between June 25, 2018, and January 22, 2021, at 9 US academic medical centers were included in a retrospective analysis. Six of the 9 representative centers (75%) had an outpatient program in place. A total of 157 patients were evaluable, including 93 (57%) in the outpatient treatment group and 64 (43%) in the inpatient treatment group. Baseline characteristics, toxicity and efficacy, and resource utilization were summarized. The most common lymphodepletion (LD) regimen was bendamustine in the outpatient group (65%) and fludarabine/cyclophosphamide (91%) in the inpatient group. The outpatient group had more patients with a Charlson Comorbidity Index of 0 (51% versus 15%; P < .001), fewer patients with an elevated lactate dehydrogenase (LDH) level above the normal range at the time of LD (32% versus 57%, P = .003) compared to the inpatient group, and a lower Endothelial Activation and Stress Index score (.57 versus 1.4; P < .001). Any-grade CRS and ICANS were lower in the outpatient group (29% versus 56% [P < .001] and 10% versus 16% [P = .051], respectively). Forty-two outpatient tisa-cel recipients (45%) required an unplanned admission, with a median length of stay of 5 days (range, 1 to 27 days), compared to 13 days (range, 4 to 38 days) in the inpatient group. The median number of tocilizumab doses administered was similar in the 2 groups as were the rate of intensive care unit (ICU) transfer (5% versus 8%; P = .5) and median length of ICU stay (6 days versus 5 days; P = .7). There were no toxicity-related deaths in the 30 days post-CAR-T infusion in either group. Progression-free survival and overall survival were similar in the 2 groups. With careful patient selection, outpatient tisa-cel administration is feasible and associated with similar efficacy outcomes as inpatient treatment. Outpatient toxicity monitoring and management may help optimize healthcare resource utilization.
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Carcinoma , Linfoma no Hodgkin , Receptores Quiméricos de Antígenos , Humanos , Adolescente , Pacientes Ambulatorios , Estudios Retrospectivos , Recurrencia Local de Neoplasia , Linfoma no Hodgkin/tratamiento farmacológicoRESUMEN
OBJECTIVES: This study sought to assess whether body mass index (BMI) was associated with subclinical left ventricular (LV) systolic dysfunction in African-American individuals. BACKGROUND: Higher BMI is a risk factor for cardiovascular disease, including heart failure. Obesity disproportionately affects African Americans; however, the association between higher BMI and LV function in African Americans is not well understood. METHODS: Peak systolic circumferential strain (ECC) was measured by tagged cardiac magnetic resonance in 1,652 adult African-American participants of the Jackson Heart Study between 2008 and 2012. We evaluated the association between BMI and ECC in multivariate linear regression and restricted cubic spline analyses adjusted for prevalent cardiovascular disease, conventional cardiovascular risk factors, LV mass, and ejection fraction. In exploratory analyses, we also examined whether inflammation, insulin resistance, or volume of visceral adipose tissue altered the association between BMI and ECC. RESULTS: The proportions of female, nonsmokers, diabetic, and hypertensive participants rose with increase in BMI. In multivariate-adjusted models, higher BMI was associated with worse ECC (ß = 0.052; 95% confidence interval: 0.028 to 0.075), even in the setting of preserved LV ejection fraction. Higher BMI was also associated with worse ECC when accounting for markers of inflammation (C-reactive protein, E-selection, and P-selectin), insulin resistance, and volume of visceral adipose tissue. CONCLUSIONS: Higher BMI is significantly associated with subclinical LV dysfunction in African Americans, even in the setting of preserved LV ejection fraction.