Risk of bleeding and significant thrombocytopenia in cancer patients treated with immune checkpoint inhibitors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15000-e15000
Author(s):  
Tariq Zuheir Kewan ◽  
Ramsha Ahmed ◽  
Sura Alqaisi ◽  
Fahrettin Covut ◽  
Monica Flores ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
Cancer Patients ◽  
Checkpoint Inhibitors ◽  
Anticoagulation Therapy ◽  
Cleveland Clinic ◽  
Immune Checkpoints ◽  
Risk Of Bleeding ◽  
Increased Risk ◽  
Clinically Significant

e15000 Background: Immune checkpoints inhibitors (ICIs) are associated with multiple side effects. Complications can affect any organ system including; endocrine, gastrointestinal, pulmonary, and less frequently hematological system.We evaluated the risk of bleeding and significant thrombocytopenia in cancer patients (pts) treated with ICIs. Methods: Cancer pts treated with ICIs between 01/2015 and 7/2019 at Cleveland Clinic Foundation were retrospectively reviewed. Platelets (plts) count and hemoglobin (hb) level at baseline, after one month and 3 months of treatment were reviewed. Thrombocytopenia was defined as plts count < 150,000. In pts with thrombocytopenia at baseline, more than 50% drop in the plts count was considered significant. Pts were followed-up for one year after ICIs treatment initiation for significant bleeding. Results: We identified 555 cancer pts treated with ICIs. Of these pts 65% were males. Among all included pts, 53% had lung cancer, 23% had genitourinary cancers, 17% had melanoma, 3% had gastrointestinal cancers, and 5% had other cancer types. Nivolumab, pembrolizumab, ipilimumab, and atezolizumab were used in 62%, 27%, 14%, and 12% respectively. Clinically significant bleeding, thrombocytopenia after one month and 3 months of treatment were identified in 21%, 6%, and 7% respectively. Of all pts who developed bleeding, 8% had gastrointestinal bleeding, 5% had intracerebral hemorrhage, and 3 % had hemoptysis. Only 23% of the pts who developed bleeding were receiving anticoagulation therapy. In multivariate analysis, breast cancer as primary malignancy (p = .03) and atezolizumab (p = 0.02) were predictors of clinically significant bleeding. Also, nivolumab was associated with increased risk of significant thrombocytopenia after one month of treatment (p = .02). There was no significant association between the use of specific medication and the development of significant anemia. Median overall survival time was not statistically different in patients who had bleeding compared to no bleeding group, 12.6 months (95% CI:10.8-14.5) and 12.4 months (95% CI:10.3-15) respectively (p = .21). Conclusions: In this cohort study, atezolizumab and breast cancer were significantly associated with increased risk of bleeding. The use of nivolumab was associated with a greater risk of thrombocytopenia after one month of treatment. Prospective studies are needed for better understanding of the hematological side effects of ICIs.

scholarly journals CD73-Mediated Immunosuppression Is Linked to a Specific Fibroblast Population That Paves the Way for New Therapy in Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5878
Author(s):  
Ilaria Magagna ◽  
Nicolas Gourdin ◽  
Yann Kieffer ◽  
Monika Licaj ◽  
Rana Mhaidly ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Checkpoint Inhibitors ◽  
Immune Checkpoints ◽  
Breast Cancer Patients ◽  
Large Collection ◽  
Functional Assays ◽  
Regulatory T Lymphocytes ◽  
Potential Clinical Benefit ◽  
Cd73 Expression

Background: Cancer-associated fibroblasts (CAF) are heterogeneous with multiple functions in breast cancer. Recently, we identified a specific CAF subpopulation (referred to as CAF-S1), which promotes immunosuppression and immunotherapy resistance. Methods and Results: Here, by studying a large collection of human samples, we highlight the key function of CD73/NT5E in CAF-S1-mediated immunosuppression in breast cancer. We first reveal that CD73 protein level specifically accumulates in CAF-S1 in breast cancer patients. Interestingly, infiltration of regulatory T lymphocytes (Tregs) is significantly correlated with CD73 expression in stroma but not in epithelium, indicating that CD73 contributes to immunosuppression when expressed in CAF-S1 and not in tumor cells. By performing functional assays based on relevant systems using primary CAF-S1 isolated from patients, we demonstrate that CAF-S1 increase the content in both PD-1+ and CTLA-4+ Tregs. Importantly, the use of a blocking anti-CD73 antibody on CAF-S1 reduces CAF-S1-mediated immunosuppression by preventing expression of these immune checkpoints on Tregs. Conclusions: Our data support the potential clinical benefit of using both anti-CD73 and immune-checkpoint inhibitors in breast cancer patients for inhibiting CAF-S1-mediated immunosuppression and enhancing anti-tumor immune response.

scholarly journals The therapy is making me sick: how online portal communications between breast cancer patients and physicians indicate medication discontinuation

2018 ◽  
Vol 25 (11) ◽  
pp. 1444-1451 ◽  
Author(s):  
Zhijun Yin ◽  
Morgan Harrell ◽  
Jeremy L Warner ◽  
Qingxia Chen ◽  
Daniel Fabbri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
Cancer Patients ◽  
Hormonal Therapy ◽  
Medical Center ◽  
Healthcare Providers ◽  
Breast Cancer Patients ◽  
Online Portal ◽  
Medication Discontinuation ◽  
Increased Risk

Abstract Objective Online platforms have created a variety of opportunities for breast patients to discuss their hormonal therapy, a long-term adjuvant treatment to reduce the chance of breast cancer occurrence and mortality. The goal of this investigation is to ascertain the extent to which the messages breast cancer patients communicated through an online portal can indicate their potential for discontinuing hormonal therapy. Materials and Methods We studied the de-identified electronic medical records of 1106 breast cancer patients who were prescribed hormonal therapy at Vanderbilt University Medical Center over a 12-year period. We designed a data-driven approach to investigate patients’ patterns of messaging with healthcare providers, the topics they communicated, and the extent to which these messaging behaviors associate with the likelihood that a patient will discontinue a prescribed 5-year regimen of therapy. Results The results indicates that messaging rate over time [hazard ratio (HR) = 1.373, P = 0.002], mentions of side effects (HR = 1.214, P = 0.006), and surgery-related topics (HR = 1.170, P = 0.034) were associated with increased risk of early medication discontinuation. In contrast, seeking professional suggestions (HR = 0.766, P = 0.002), expressing gratitude to healthcare providers (HR = 0.872, P = 0.044), and mentions of drugs used to treat side effects (HR = 0.807, P = 0.013) were associated with decreased risk of medication discontinuation. Discussion and Conclusion This investigation suggests that patient-generated content can inform the study of health-related behaviors. Given that approximately 50% of breast cancer patients do not complete a course of hormonal therapy as described, the identification of factors associated with medication discontinuation can facilitate real-time interventions to prevent early discontinuation.

scholarly journals Individual radiosensitivity in a breast cancer collective is changed with the patients’ age

2014 ◽  
Vol 48 (1) ◽  
pp. 80-86 ◽  
Author(s):  
Judith Auer ◽  
Ulrike Keller ◽  
Manfred Schmidt ◽  
Oliver Ott ◽  
Rainer Fietkau ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
Cancer Patients ◽  
Older Patients ◽  
Breast Cancer Patients ◽  
Healthy Individuals ◽  
Blood Samples ◽  
Individual Radiosensitivity ◽  
Increased Risk

Abstract Background. Individual radiosensitivity has a crucial impact on radiotherapy related side effects. Our aim was to study a breast cancer collective for its variation of individual radiosensitivity depending on the patients’ age. Materials and methods. Peripheral blood samples were obtained from 129 individuals. Individual radiosensitivity in 67 breast cancer patients and 62 healthy individuals was estimated by 3-color fluorescence in situ hybridization. Results. Breast cancer patients were distinctly more radiosensitive compared to healthy controls. A subgroup of 9 rather radiosensitive and 9 rather radio-resistant patients was identified. A subgroup of patients aged between 40 and 50 was distinctly more radiosensitive than younger or older patients. Conclusions. In the breast cancer collective a distinct resistant and sensitive subgroup is identified, which could be subject for treatment adjustment. Preliminary results indicate that especially in the range of age 40 to 50 patients with an increased radiosensitivity are more frequent and may have an increased risk to suffer from therapy related side effects.

Radiation therapy and immune-related side effects in patients treated with PD-1 inhibitors.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 207-207
Author(s):  
Nadine Abdallah ◽  
Suketu Nagin Patel ◽  
Misako Nagasaka ◽  
Seongho Kim ◽  
Harold E. Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Radiation Therapy ◽  
Side Effects ◽  
Cancer Patients ◽  
Checkpoint Inhibitors ◽  
Antitumor Effects ◽  
Lung Cancer Patients ◽  
Immune Mediated ◽  
Increased Risk ◽  
Thoracic Radiation

207 Background: Checkpoint inhibitors exert their antitumor effects by producing a heightened immune state, and inadvertently give rise to immune-mediated toxicities, including pneumonitis and hypothyroidism. We investigated whether these side effects were more common in patients who were treated with both PD-1 inhibitors and radiation. Methods: Our institution’s pharmacy database was used to collect data on patients who received ≥ 1 dose of PD-1 inhibitors, with or without radiation before August 31, 2016. Adverse effects of hypothyroidism, and pneumonitis were recorded and graded based on CTCAEv4. A logistic regression analysis was performed between radiation and hypothyroidism among patients with Hodgkin’s lymphoma (HL) and head and neck squamous cell carcinoma (HNSCC) and between radiation therapy (RT) and pneumonitis in lung cancer patients. Results: 231 patients received at least one dose of PD-1 inhibitors prior to data cut-off. Median age was 65 (24-92). There were 125 patients (54%) with lung cancer, 18 (8%) with HL and 9 (4%) with HNSCC. 115 patients received radiation. HL and HNSCC patients had higher odds to experience hypothyroidism (adjusted p = 0.023) but this did not seem to be due to RT exposure [HR:0.156, 95% CI 0.008-1.122, p = 0.110]. Lung cancer patients with thoracic radiation had higher odds to experience pneumonitis [HR:2.206, 95% CI 0.451-15.931] although this was not statistically significant (p = 0.358). Conclusions: There was no association between RT and hypothyroidism. Our results suggested a possible increased risk of pneumonitis with thoracic radiation among lung cancer patients treated with PD-1 inhibitors, although statistically insignificant. Larger prospective studies are needed to further delineate this effect.

scholarly journals From Oncogenic Signaling Pathways to Single-Cell Sequencing of Immune Cells: Changing the Landscape of Cancer Immunotherapy

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2278
Author(s):  
Afshin Derakhshani ◽  
Zeinab Rostami ◽  
Hossein Safarpour ◽  
Mahdi Abdoli Shadbad ◽  
Niloufar Sadat Nourbakhsh ◽  
...  
Keyword(s):  
Single Cell ◽  
Signaling Pathways ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Cancer Development ◽  
Immune Checkpoints ◽  
Single Cell Sequencing ◽  
Increased Risk

Over the past decade, there have been remarkable advances in understanding the signaling pathways involved in cancer development. It is well-established that cancer is caused by the dysregulation of cellular pathways involved in proliferation, cell cycle, apoptosis, cell metabolism, migration, cell polarity, and differentiation. Besides, growing evidence indicates that extracellular matrix signaling, cell surface proteoglycans, and angiogenesis can contribute to cancer development. Given the genetic instability and vast intra-tumoral heterogeneity revealed by the single-cell sequencing of tumoral cells, the current approaches cannot eliminate the mutating cancer cells. Besides, the polyclonal expansion of tumor-infiltrated lymphocytes in response to tumoral neoantigens cannot elicit anti-tumoral immune responses due to the immunosuppressive tumor microenvironment. Nevertheless, the data from the single-cell sequencing of immune cells can provide valuable insights regarding the expression of inhibitory immune checkpoints/related signaling factors in immune cells, which can be used to select immune checkpoint inhibitors and adjust their dosage. Indeed, the integration of the data obtained from the single-cell sequencing of immune cells with immune checkpoint inhibitors can increase the response rate of immune checkpoint inhibitors, decrease the immune-related adverse events, and facilitate tumoral cell elimination. This study aims to review key pathways involved in tumor development and shed light on single-cell sequencing. It also intends to address the shortcomings of immune checkpoint inhibitors, i.e., their varied response rates among cancer patients and increased risk of autoimmunity development, via applying the data from the single-cell sequencing of immune cells.

scholarly journals Comparing the efficacy and side-effects of PDLASTA® (Pegfilgrastim) with PDGRASTIM® (Filgrastim) in breast cancer patients: a non-inferiority randomized clinical trial

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Safa Najafi ◽  
Maryam Ansari ◽  
Vahid Kaveh ◽  
Shahpar Haghighat
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Single Dose ◽  
Side Effects ◽  
Randomized Clinical Trial ◽  
Cancer Patients ◽  
Injection Site Reaction ◽  
Study Groups ◽  
Breast Cancer Patients ◽  
Significant Difference

Abstract Background The objective of this study was to compare the efficacy and side effects of a single dose (Pegfilgrastim or PDL) or repeated six daily injections (Filgrastim or PDG) during chemotherapy courses in breast cancer patients in a non-inferiority clinical trial. Methods In this randomized clinical trial, 80 patients were recruited and allocated randomly to two equal arms. In one group, a single subcutaneous dose of PDL was injected the day after receiving the chemotherapy regimen in each cycle. The second arm received a subcutaneous injection of PDG for six consecutive days in each cycle of treatment. The side effects of GCF treatment and its effect on blood parameters were compared in each cycle and during eight cycles of chemotherapy. Results Hematologic parameters showed no significant differences in any of the treatment courses between the two study groups. The comparison of WBC (p = 0.527), Hgb (p = 0.075), Platelet (p = 0.819), Neutrophil (p = 0.575), Lymphocyte (p = 705) and ANC (p = 0.675) changes during the eight courses of treatment also revealed no statistically significant difference between the two study groups. Side effects including headache, injection site reaction and muscle pain had a lower frequency in patients receiving PDL drugs. Conclusion It seems that PDL is non-inferior in efficacy and also less toxic than PDG. Since PDL can be administered in a single dose and is also less costly, it can be regarded as a cost-effective drug for the treatment of chemotherapy-induced neutropenia. Trial registration IRCT20190504043465N1, May 2019.

The burden of polypharmacy and drug–drug interactions in older cancer patients treated with immunotherapy

2021 ◽  
pp. 107815522110120
Author(s):  
Deniz C Guven ◽  
Gozde Kavgaci ◽  
Oktay H Aktepe ◽  
Hasan C Yildirim ◽  
Taha K Sahin ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Cancer Patients ◽  
Injury Risk ◽  
Checkpoint Inhibitors ◽  
High Rate ◽  
Potentially Inappropriate Medications ◽  
Inappropriate Prescription ◽  
Prescription Practices ◽  
Increased Risk ◽  
Older Cancer Patients

Introduction Polypharmacy is a common problem in older cancer patients, although the data about polypharmacy and potentially inappropriate prescription practices is limited in patients treated with immune checkpoint inhibitors (ICIs). Therefore, we aimed to evaluate the polypharmacy frequency and drug-drug interactions in older cancer patients (≥65 years) treated with ICIs. Methods A total of 70 geriatric patients with advanced cancer were included. The polypharmacy was defined as regular use of 5 or more drugs. The START/STOPP Criteria Version 2 was used for the potentially inappropriate medications (PIM) and potential prescription omissions (PPO). The Medscape Drug Interaction Checker was used for potential drug-drug interactions. Results The patients had a median of 6 regular drugs, and polypharmacy was present in 77.1%. The polypharmacy risk was significantly increased in patients over 75 years of age (p = 0.028) and with opioid use (p = 0.048). The 50% of patients had category D or X interactions. Patients with higher Charlson Comorbidity Index had significantly increased risk for drug interactions (CCI ≤10 vs. >10, p = 0.017). The PIMs were present in 44.3% and the PPOs in 68.6% of the patients. While the overall survival and immune related adverse events were similar according to polypharmacy, in patients using seven or more drugs, the acute kidney injury risk was increased (HR: 4.667, p = 0.038). Conclusion In this study, we observed a high rate of polypharmacy and inappropriate prescription practices in ICI-treated patients. These issues pointed out the need for improved general medical care and attention for better comedication management in ICI-treated patients.

scholarly journals An Exploration of Heart Failure Risk in Breast Cancer Patients Receiving Anthracyclines with or without Trastuzumab in Thailand: A Retrospective Study

2021 ◽  
Vol 11 (3) ◽  
pp. 484-493
Author(s):  
Jukapun Yoodee ◽  
Aumkhae Sookprasert ◽  
Phitjira Sanguanboonyaphong ◽  
Suthan Chanthawong ◽  
Manit Seateaw ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Cancer Patients ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Breast Cancer Patients ◽  
Ventricular Ejection Fraction ◽  
Factors Associated ◽  
Palliative Intent ◽  
Increased Risk

Anthracycline-based regimens with or without anti-human epidermal growth factor receptor (HER) 2 agents such as trastuzumab are effective in breast cancer treatment. Nevertheless, heart failure (HF) has become a significant side effect of these regimens. This study aimed to investigate the incidence and factors associated with HF in breast cancer patients treated with anthracyclines with or without trastuzumab. A retrospective cohort study was performed in patients with breast cancer who were treated with anthracyclines with or without trastuzumab between 1 January 2014 and 31 December 2018. The primary outcome was the incidence of HF. The secondary outcome was the risk factors associated with HF by using the univariable and multivariable cox-proportional hazard model. A total of 475 breast cancer patients were enrolled with a median follow-up time of 2.88 years (interquartile range (IQR), 1.59–3.93). The incidence of HF was 3.2%, corresponding to an incidence rate of 11.1 per 1000 person-years. The increased risk of HF was seen in patients receiving a combination of anthracycline and trastuzumab therapy, patients treated with radiotherapy or palliative-intent chemotherapy, and baseline left ventricular ejection fraction <65%, respectively. There were no statistically significant differences in other risk factors for HF, such as age, cardiovascular comorbidities, and cumulative doxorubicin dose. In conclusion, the incidence of HF was consistently high in patients receiving combination anthracyclines trastuzumab regimens. A reduced baseline left ventricular ejection fraction, radiotherapy, and palliative-intent chemotherapy were associated with an increased risk of HF. Intensive cardiac monitoring in breast cancer patients with an increased risk of HF should be advised to prevent undesired cardiac outcomes.

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