Background
An elevated neutrophil‐to‐lymphocyte ratio (NLR) is associated with poor survival in patients with cancer, including those who receive immunotherapies. The authors sought to investigate ...NLR as a biomarker of treatment outcomes in patients with melanoma who were treated with PD‐1 inhibition.
Methods
Patients undergoing initial treatment with PD‐1 inhibitor monotherapy for stage IV melanoma at a single center from 2012 to 2015 were included. Clinical characteristics and the NLR at baseline and before subsequent treatment cycles were collected. The time to treatment failure (TTF) and overall survival (OS) were evaluated using Kaplan‐Meier and landmark analyses.
Results
Among 224 study patients, 63 (28%) had a baseline NLR ≥5. The baseline NLR was significantly associated with Eastern Cooperative Oncology Group performance status and the number of involved metastatic sites. With a median follow‐up of 39 months in survivors, a baseline NLR ≥5 was independently associated with shorter OS (hazard ratio, 2.0; 95% CI, 1.3‐2.9) and TTF (hazard ratio, 1.7; 95% CI, 1.2‐2.4). An NLR increase ≥30% during the first 2 cycles of treatment was associated with worse OS (median, 47 vs 13.5 months; P < .001) and a trend toward shorter TTF (12.8 vs 5.9 months; P = .05). A combined baseline NLR ≥5 and an NLR increase ≥30% identified a small cohort with markedly shortened OS (median, 5.8 months) and TTF (median, 1.8 months).
Conclusions
Elevated baseline NLR and an increased NLR early during treatment are prognostic for TTF and OS in patients who have melanoma treated with PD‐1 inhibitor monotherapy. Combined, these biomarkers can widely risk‐stratify patients for treatment failure and survival.
A pretreatment neutrophil‐to‐lymphocyte ratio (NLR) ≥5 and an increase ≥30% in the NLR are independently prognostic for treatment failure and worse overall survival in patients who have melanoma treated with PD‐1 inhibitor monotherapy. The pretreatment NLR is associated with both tumor and host factors, suggesting that the NLR reflects a complex interaction between the tumor and the host immune response.
Objective
A dearth of studies focusing on young women (<40 years) with breast cancer have hampered the understanding of the type, prevalence, and predictors of sexual dysfunction and reproductive ...concerns in this population.
Methods
Data were collected from 181 women (response rate = 60%) diagnosed with breast cancer approximately 2 years previously (age 21‐39) using the Swedish National Quality Registry for Breast Cancer and a survey including standardized measures of sexual dysfunction, reproductive concerns, body image, and health‐related quality of life. Multivariable logistic binary regression analyses were used to identify predictors of sexual dysfunction and reproductive concerns.
Results
Sexual dysfunction in at least one domain was reported by 68% of the women, and a high level of reproductive concerns in at least one dimension was reported by 58%. Model results showed that current endocrine treatment was a significant predictor of dysfunction related to lubrication (OR 3.8, 95% CI 1.2‐12.1) and vaginal discomfort (OR 8.7, 95% CI 1.5‐51.5). Negative body image was related to satisfaction with sex life (OR 1.1, 95% CI 1.0‐1.2). A high level of reproductive concerns was predicted by a wish for (additional) children in the future (OR 3.4, 95% CI 1.1‐10.2) and by previous chemotherapy (OR 2.5, 95% CI 1.1‐5.9).
Conclusions
Sexual dysfunction and reproductive concerns are common in young women with breast cancer. Current endocrine treatment, previous chemotherapy, a negative body image, and a wish for children in the future predict higher level of problems.
Tumor-intrinsic features may render large B-cell lymphoma (LBCL) insensitive to CD19-directed chimeric antigen receptor T cells (CAR-T). We hypothesized that TP53 genomic alterations are detrimental ...to response outcomes in LBCL treated with CD19-CAR-T.
Patients with LBCL treated with CD19-CAR-T were included. Targeted next-generation sequencing was performed on pre-CAR-T tumor samples in a subset of patients. Response and survival rates by histologic, cytogenetic, and molecular features were assessed. Within a cohort of newly diagnosed LBCL with genomic and transcriptomic profiling, we studied interactions between cellular pathways and
status.
We included 153 adults with relapsed or refractory LBCL treated with CD19-CAR-T (axicabtagene ciloleucel 50%, tisagenlecleucel 32%, and lisocabtagene maraleucel 18%). Outcomes echoed pivotal trials: complete response (CR) rate 54%, median overall survival (OS) 21.1 months (95% CI, 14.8 to not reached), and progression-free survival 6 months (3.4 to 9.7). Histologic and cytogenetic LBCL features were not predictive of CR. In a subset of 82 patients with next-generation sequencing profiling, CR and OS rates were comparable with the unsequenced cohort.
alterations (mutations and/or copy number alterations) were common (37%) and associated with inferior CR and OS rates in univariable and multivariable regression models; the 1-year OS in
-altered LBCL was 44% (95% CI, 29 to 67) versus 76% (65 to 89) in wild-type (
= .012). Transcriptomic profiling from a separate cohort of patients with newly diagnosed lymphoma (n = 562) demonstrated that
alterations are associated with dysregulation of pathways related to CAR-T-cell cytotoxicity, including interferon and death receptor signaling pathway and reduced CD8 T-cell tumor infiltration.
is a potent tumor-intrinsic biomarker that can inform risk stratification and clinical trial design in patients with LBCL treated with CD19-CAR-T. The role of TP53 should be further validated in independent cohorts.
CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has become a breakthrough treatment of patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). However, despite the ...high initial response rate, the majority of adult patients with B-ALL progress after CD19 CAR T-cell therapy. Data on the natural history, management, and outcome of adult B-ALL progressing after CD19 CAR T cells have not been described in detail. Herein, we report comprehensive data of 38 adult patients with B-ALL who progressed after CD19 CAR T therapy at our institution. The median time to progression after CAR T-cell therapy was 5.5 months. Median survival after post-CAR T progression was 7.5 months. A high disease burden at the time of CAR T-cell infusion was significantly associated with risk of post-CAR T progression. Thirty patients (79%) received salvage treatment of post-CAR T disease progression, and 13 patients (43%) achieved complete remission (CR), but remission duration was short. Notably, 7 (58.3%) of 12 patients achieved CR after blinatumomab and/or inotuzumab administered following post-CAR T failure. Multivariate analysis revealed that a longer remission duration from CAR T cells was associated with superior survival after progression following CAR T-cell therapy. In summary, overall prognosis of adult B-ALL patients progressing after CD19 CAR T cells was poor, although a subset of patients achieved sustained remissions to salvage treatments, including blinatumomab, inotuzumab, and reinfusion of CAR T cells. Novel therapeutic strategies are needed to reduce risk of progression after CAR T-cell therapy and improve outcomes of these patients.
The activity of anti-CD19 CAR T cell therapy in chronic lymphocytic leukemia (CLL) with Richter's transformation (RT) to aggressive large B cell lymphoma (LBCL) is largely unknown. In a multicenter ...retrospective study, we report the safety and efficacy of CAR T cell therapy in patients with RT (n=30) compared to patients with aggressive B cell lymphoma (n=283) and patients with transformed indolent Non-Hodgkins Lymphoma (iNHL) (n=141) between April 2016 and January 2023. Two-thirds of patients received prior therapy for CLL before RT and 89% of them received B-cell receptor and B-cell lymphoma 2 (BCL-2) inhibitors. Toxicities of CAR T cell therapy in RT were similar to other lymphomas, with no fatalities related to cytokine release syndrome or immune effector-cell associated neurotoxicity synderome. The 100-day overall response rate and complete response rates in patients with RT were 57% and 47%, respectively. With a median follow up of 19 months, the median overall survival (OS) was 9.9 months in patients with RT compared to 18 months in de-novo LBCL and not reached in patients with transformed iNHL. The OS at 12 months was 45% in patients with RT compared with 62% and 75% in patients with de novo LBCL and transformed iNHL, respectively. In a multivariate analysis, worse OS was associated with RT histology, elevated LDH, and more prior lines of therapy. CAR T cell therapy can salvage a proportion of patients with CLL and RT exposed to prior targeted agents; however, efficacy in RT is inferior compared to de novo LBCL and transformed iNHL
CD19-targeted chimeric antigen receptor (CAR) T cell therapy is an effective treatment for diffuse large B cell lymphoma (DLBCL). In addition to cytokine release syndrome (CRS) and immune effector ...cell-associated neurotoxicity (ICANS), B cell aplasia and hypogammaglobulinemia are common toxicities predisposing these patients to infections. We analyzed 60 patients with DLBCL treated with FDA-approved CD19 CAR T cells and report the incidence, risk factors, and management of infections during the first year after treatment. A total of 101 infectious events were observed, including 25 mild, 51 moderate, 23 severe, 1 life-threatening, and 1 fatal infection. Bacteria were the most common causative pathogens. The cumulative incidence of overall, bacterial, severe bacterial, viral, and fungal infection at 1 year were 63.3%, 57.2%, 29.6%, 44.7%, and 4%, respectively. In multivariate analyses, the use of systemic corticosteroids for the management of CRS or ICANS was associated with an increased risk of infections and prolonged admission. Impaired performance status and history of infections within 30 days before CAR T cell therapy was a risk factor for severe bacterial infection. In conclusion, infections were common within the first 60 days after CAR T cell therapy, however, they were not associated with an increased risk of death.
Trastuzumab improves outcomes in patients with ERBB2-positive (formerly HER2) breast cancer but is associated with treatment-induced cardiotoxicity, most commonly manifest by an asymptomatic decline ...in left ventricular ejection fraction (LVEF). Little is known to date regarding the long-term effects of treatment-induced cardiotoxicity on cardiopulmonary function in patients who survive trastuzumab-treated breast cancer.
To determine whether treatment-induced cardiotoxicity recovers or is associated with long-term cardiopulmonary dysfunction in survivors of ERBB2-positive breast cancer.
This cross-sectional case-control study enrolled patients with nonmetastatic ERBB2-positive breast cancer after completion of trastuzumab-based therapy (median, 7.0 interquartile range (IQR), 6.2-8.7 years after therapy) who met 1 of 2 criteria: (1) cardiotoxicity (TOX group) developed during trastuzumab treatment (ie, asymptomatic decrease of LVEF≥10% from baseline to <55% n = 22) or (2) no evidence of cardiotoxicity during trastuzumab treatment (NOTOX group n = 20). Patients were treated at the Memorial Sloan Kettering Cancer Center. Fifteen healthy control participants (HC group) were also enrolled for comparison purposes. All groups were frequency matched by age strata (<55, 55-64, and ≥65 years). Data were collected from September 9, 2016, to August 10, 2018, and analyzed from November 20, 2018, to August 12, 2019.
Speckle-tracking echocardiography and maximal cardiopulmonary exercise testing were performed to measure indices of left ventricular function (including LVEF and global longitudinal strain GLS) and peak oxygen consumption (peak VO2).
A total of 57 participants (median age, 60.8 IQR, 52.7-65.7 years) were included in the analysis. Overall, 38 of 42 patients with breast cancer (90%) were treated with anthracyclines before trastuzumab. Resting mean (SD) LVEF was significantly lower in the TOX group (56.9% 5.2%) compared with the NOTOX (62.4% 4.0%) and HC (65.3% 2.9%) groups; similar results were found for GLS (TOX group, -17.8% 2.2%; NOTOX group, -19.8% 2.2%; HC group, -21.3% 1.8%) (P < .001). Mean peak VO2 in the TOX group (22.9 4.4 mL/kg/min) was 15% lower compared with the NOTOX group (27.0 5.3 mL/kg/min; P = .03) and 25% lower compared with the HC group (30.5 3.4 mL/ kg/min; P < .001). In patients with breast cancer, GLS was significantly associated with peak VO2 (β coefficient, -0.75; 95% CI, -1.32 to -0.18).
Treatment-induced cardiotoxicity appears to be associated with long-term marked impairment of cardiopulmonary function and may contribute to increased risk of late-occurring cardiovascular disease in survivors of ERBB2-positive breast cancer.
To explore the correlation between health-illness transition (HIT) experiences and distress among patients with pancreatic cancer.
55 patients with a diagnosis of pancreatic cancer receiving ...chemotherapy at a tertiary cancer center in New York.
A prospective correlational study was performed to explore the frequency, extent, and management of HITs. HITs were evaluated using the Measurement of Transitions in Cancer Scale, and distress was measured with the National Comprehensive Cancer Network Distress Thermometer.
All patients experienced at least one HIT. The extent of HITs decreased over time. Patients reported that they managed HITs moderately well. There was a significant correlation between unmanaged HITs and distress. As distress increased, the extent of the physical and emotional HITs increased and management worsened.
HITs are ubiquitous among patients diagnosed with pancreatic cancer. Associated distress inhibits management. Nurses are well suited to assess for potential HITs and to support self-management of HITs.
Fecal microbiota transplant (FMT) is recommended for Clostridium difficile infection (CDI) treatment; however, use in solid organ transplantation (SOT) patients has theoretical safety concerns. This ...multicenter, retrospective study evaluated FMT safety, effectiveness, and risk factors for failure in SOT patients. Primary cure and overall cure were defined as resolution of diarrhea or negative C difficile stool test after a single FMT or after subsequent FMT(s) ± anti‐CDI antibiotics, respectively. Ninety‐four SOT patients underwent FMT, 78% for recurrent CDI and 22% for severe or fulminant CDI. FMT‐related adverse events (AE) occurred in 22.3% of cases, mainly comprising self‐limiting conditions including nausea, abdominal pain, and FMT‐related diarrhea. Severe AEs occurred in 3.2% of cases, with no FMT‐related bacteremia. After FMT, 25% of patients with underlying inflammatory bowel disease had worsening disease activity, while 14% of cytomegalovirus‐seropositive patients had reactivation. At 3 months, primary cure was 58.7%, while overall cure was 91.3%. Predictors of failing a single FMT included inpatient status, severe and fulminant CDI, presence of pseudomembranous colitis, and use of non‐CDI antibiotics at the time of FMT. These data suggest FMT is safe in SOT patients. However, repeated FMT(s) or additional antibiotics may be needed to optimize rates of cure with FMT.
Fecal microbiota transplantation (FMT) for the treatment of Clostridium difficile infection in patients with a history of solid organ transplantation is associated with low adverse event rates and high rates of cure, especially with repeat FMT(s) and/or additional antibiotics.
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