Antineoplastic Regimens Research Articles

P1598: SARS-COV2 INFECTION IN FULLY VACCINATED PATIENTS WITH LYMPHOID MALIGNANCIES DURING THE “THIRD WAVE”: A SINGLE-CENTER EXPERIENCE OF 57 PATIENTS.

Background: COVID-19-related mortality rates are increased in hematological patients and those with lymphoid malignancies look particularly vulnerable to SARS-CoV-2 infection, due to the characteristics of their disease and the anti-neoplastic treatments used. Vaccines against SARS-CoV-2 have been rapidly developed. However, patients treated with anti-CD20 monoclonal antibodies have shown lower seroconversion rates after receiving mRNA SARS-CoV-2 vaccines. Several antiviral agents, such as molnupiravir and remdesivir, and some monoclonal antibodies have been also used for the management of COVID-19 in order to reduce the risk of progression to severe disease. Aims: The aim of this study was to evaluate the outcome of SARS-Cov2 infection in a population of patients affected by chronic lymphocytic leukemia (CLL), Hodgkin lymphoma (HL), B- and T-cell non-Hodgkin lymphomas (NHLs) during the so-called “third wave” of SARS-CoV-2 pandemic. Methods: We performed a retrospective analysis of 57 patients affected by CLL (n. 12), HL (n. 8), B (n. 34) and T-cell (n. 3) NHLs who experienced SARS-CoV2 infection between December, 1, 2021, and February, 26, 2022. All patients had received a complete cycle of anti-SARS-Cov2 vaccine before infection. They were diagnosed by RT-PCR or by antigen rapid test on nasopharyngeal swabs. We collected data about sex, age, histological features, anti-neoplastic regimens, symptoms, hospitalization, mortality, use of antiviral drugs or monoclonal antibodies for the treatment of COVID-19, time to SARS-CoV-2 negativity. Results: The median age of the whole group was 58 (18-94) years. Thirty-two patients (56%) were male, while 26 (44%) were female. As far as histological features are concerned, follicular lymphoma was the most frequent one (35%). Within the last 12 months before SARS-CoV-2 infection, 40 patients (70%) had received treatment for their hematological disease, 17 (30%) were on anti-CD20 maintenance, 12 (21%) on treatment with immuno-chemotherapy (ICT), 6 (11%) on ibrutinib, 3 (5%) on checkpoint inhibitors and 3 (5%) were on chemotherapy only. All patients had received two doses of anti-SARS-CoV-2 vaccines, and 77% of them a further, booster dose. The most common symptoms at presentation were fever, cough, muscle pain, headache, fatigue. Overall, 15 (26%) patients were hospitalized, and, among them, 4 (7%) were admitted to intensive care units (ICUs). Fifteen (26%) patients received an antiviral drug, while 4 (7%) hospitalized patients received monoclonal antibodies for the treatment COVID-19. Average time length to reach a negative test for SARS-CoV-2 was 17 days. Sixteen (28%) patients remained positive after 5-to-61 days and 6 (11%) patients died. At univariate analysis, CLL and Diffuse Large B-Cell Lymphoma (DLBCL) (p 0.026), as well as treatment with ICT or BTK inhibitors (p 0.002), were significantly associated to a worse overall survival (OS). Notably, maintenance therapy with anti-CD20 monoclonal antibodies as single agents had no impact on OS. Moreover, the cumulative incidence of nasopharyngeal swabs turned negative was significantly lower in patients treated with ICT (p 0.001). Booster dose and antiviral treatments did non influence neither OS, nor time to a negative viral test. Summary/Conclusion: In our study histological subtype and type of treatment, but not antiviral therapies, had prognostic impact on the outcome of SARS COV 2 infection in patients with lymphoproliferative disorders during the current phase of pandemic. These findings warrant to be further investigated in larger series.

PB2283: COVID-19 (SARS-COV-2 INFECTION) IN LYMPHOMA PATIENTS

Background: Observations from initial case series suggested that cancer patients in general might have an unfavorable outcome following coronavirus disease 2019 (COVID-19), due to their underlying conditions and cytotoxic treatments. Lymphoma patients may be especially vulnerable, due to the immunodeficiency and immune dysregulation caused by the lymphoma itself and the antitumor treatments. Aims: analysis of the flow of coronavirus disease (COVID-19) in cases of the patients with non-Hodgkin’s lymphoma and Hodgkin’s lymphoma on the background of specific treatment. Patients with lymphoma appear particularly vulnerable to SARS-CoV-2 infection, only partly because of the detrimental effects of the anti-neoplastic regimens (chemotherapy, pathway inhibitors, monoclonal antibodies) on the immune system. Methods: The National Cancer Institute conducted a retrospective analysis of the course of the disease on COVID-19 from March 2020 to October 2021. The study included 87 patients. The average age of the patients was 30.4 years (from 23 to 75 years old). 60 patients had non-Hodgkin’s lymphoma, 19 patients had Hodgkin’s lymphoma, and 8 had multiple myeloma. Results: Coronavirus disease in 85 % of the patients was confirmed by PCR, in 15% - by IFM (detected IgM). Severe cases of coronavirus disease were observed in 19.23 %, moderate severity - in 53.8% of the patients, light- in 26.9%. Covid-19 pneumonia was diagnosed in 74.71% of the patients. The duration of coronavirus disease ranged from 7 to 60 days, on average of 26.56 days, in cases of 22 patients (25.28 %) - more than 30 days. 18 patients (20.68%) died due to complications of coronavirus disease. Fatalities were more common among patients with DBCL - 29.16 %, and among patients with recurrent and refractory forms of the disease - 33.33 %. The type of anticancer therapy affected the outcome of the disease, mortality was more common among patients receiving chemotherapy RB and RdaEPOCH regimens, respectively 31.57 % and 40%. Among of toxicity after continued special treatment in 11.5 % patients were recorded complications - pulmonitis, 8 patients with thromboembolic complications, 1 patient developed pulmonary embolism. Patients after infection before the start of special treatment required a recovery period, which averaged 21.7 days, ranging from 7 to 60 days. Summary/Conclusion: COVID-19 infection is of particular concern for morbidity and mortality of patients with lymphoma due to their immunodeficiency status and 11.5% caused by the disease itself and / or its treatment. Patients with lymphoproliferative diseases are more likely to have moderate COVID-19 disease, mortality from complications is higher than in cases of the population and makes up 20.68%.

S280: B-CELL MALIGNANCIES TREATED WITH TARGETED DRUGS AND SARS-COV-2 INFECTION. A EUROPEAN HEMATOLOGY ASSOCIATION SURVEY (EPICOVIDEHA)

Background: Patients with lymphoproliferative diseases (LPD) appear particularly vulnerable to SARS-CoV-2 infection, partly because of the effects of the anti-neoplastic regimens (chemotherapy, signaling pathway inhibitors, and monoclonal antibodies) on the immune system. The real impact of COVID-19 on the life expectancy of patients with different subtypes of lymphoma and targeted treatment is still unknown. Aims: The aim of this study is to describe and analyse the outcome of COVID-19 patients with underlying LPD treated with targeted drugs such as monoclonal antibodies (obinutuzumab, ofatumumab, brentuximab, nivolumab or pembrolizumab), BTK inhibitors (ibrutinib, acalabrutinib), PI3K inhibitors (idelalisib), BCL2 inhibitors (venetoclax) and IMIDs, (lenalidomide). Methods: The survey was supported by EPICOVIDEHA registry. Adult patients with baseline CLL or non-Hodgkin Lymphoma (NHL) treated with targeted drugs and laboratory-confirmed COVID-19 diagnosed between January 2020 and January 2022 were selected. Results: The study included 368 patients (CLL n=205, 55.7%; NHL n=163, 44.3%) treated with targeted drugs (Table 1). Median follow-up was 70.5 days (range 19-159). Most used targeted drugs were ITKs (51.1%), anti-CD20 other than rituximab (16%), BCL2 inhibitors (7.3%) and lenalidomide (7.9%). Of note, only 16.0% of the patients were vaccinated with 2 or more doses of vaccine at the onset of COVID-19. Pulmonary symptoms were present at diagnosis in 244 patients (66.2%). Severe COVID-19 was observed in 47.8 % patients while 21.7% were admitted to to intensive care unit (ICU), being 55 (26.8%) CLL patients and 25 (15.3%) NHL patients. More comorbidities were reported in patients with severe-critical COVID-19 compared to those with mild- asymptomatic infection (p=0.002). This difference was relevant in patients with chronic heart diseases (p=0.005). Overall, 134 patients (36.4%) died. Primary cause of death was COVID-19 in 92 patients (68.7%), LPD in 14 patients (10.4%), and a combination of both in 28 patients (20.9%).Mortality was 24.2% (89/368) at day 30 and 34.5%(127/368) at day 200. After a Cox multivariable regression age >75 years (p<0.001, HR 1.030), active malignancy (p=0.011, HR 1.574) and admission to ICU (p<0.00, HR 4.624) were observed as risk factors. Survival in patients admitted to ICU was 33.7% (LLC 38.1%, NHL 24%). Mortality rate decreased depending on vaccination status, being 34.2% in not vaccinated patients, 15.9-18% with one or two doses, decreasing to 9.7% in patients with booster dose (p<0.001). There was no difference in OS in NLH vs CLL patients (p=0.344), nor in ITKs vs no ITKs treated patients (p=0.987). Additionally, mortality rate dropped from the first semester 2020 (41.3%) to last semester 2021 (25%). Image:Summary/Conclusion: - Our results confirm that patients with B-malignancies treated with targeted drugs have a high risk of severe infection (47.8%) and mortality (36.4%) from COVID-19. - Presence of comorbidities, especially heart disease, is a risk factor for severe COVID-19 infection in our series. - Age >75 years, active malignancy at COVID-19 onset and ICU admission were mortality risk factors. - COVID-19 vaccination was a protective factor for mortality, even in this population with humoral immunity impairment. - The learning curve in the management of the infection throughout the pandemic and the development of COVID-19 treatments showed benefit in this particularly vulnerable population.

Management Practice and Drug Related Problems and Its Contributing Factors Among Cervical Cancer Patients at Oncologic Center in Ethiopia: A Hospital-Based Retrospective Study.

IntroductionIn cervical cancer therapy, there is a high prevalence of drug-related problems (DRPs) due to the high toxicity and complexity of most antineoplastic regimens. However, there is a paucity of data about DRPs among patients with cervical cancer in Ethiopia. Hence, the present study was aimed at investigating management practices and DRPs among patients diagnosed with cervical cancer.MethodsA registry-based retrospective cohort study was employed among cervical cancer patients at the oncology center of Felege Hiwot Comprehensive Specialized Hospital (FHCSH). All patients with a histologically confirmed diagnosis of cervical cancer from January 2016 to December 2020 were included. Relevant information was recorded by reviewing medical records. The possibility of DRPs was evaluated by comparing with standard guidelines. Logistic regression analysis was employed.ResultsA total of 184 cervical cancer patients were included, with a mean age of 50.2±10.7 years. A total of 216 DRPs were identified from 93 cervical cancer patients, translating to a prevalence of 50.5% and a mean of 2.32±1.11 DRPs per patient. ADR (27.3%), DDI (25%), and the need for additional drug therapy (22.2%) were the most prevalent DRPs. DRPs were associated with the presence of co-morbidity (AOR = 4.23, 95% CI = 1.78–10.05, p = 0.001), complications (AOR = 2.99, 95% CI = 1.28–6.99, p = 0.011), being treated with ≥5 medications (AOR = 5.1, 95% CI = 2.38–10.95, p < 0.001), being stage II (AOR = 0.14, 95% CI = 0.02–0.90, p = 0.038), and stage III (AOR = 0.04, 95% CI = 0.01–0.32, p = 0.003).ConclusionCisplatin-based chemotherapy was the frequently used therapeutic option. Co-morbidity and complication status, number of medication and stage of cancer were significantly associated with DRPs. The study highlights the need of clinical pharmacy services to optimize drug therapy and reduce DRPs.

Anti-neoplastic drugs for malignant pleural effusion in non-small cell lung cancer: A meta-analysis.

e21060 Background: Malignant pleural effusion (MPE) occurs in 7-23% of advanced non-small cell lung cancer (NSCLC) patients with overall survival (OS) of 8.5 months only. The optimum anti-neoplastic regimen in MPE is yet to be determined. Thus, we conducted a meta-analysis to determine the optimum anti-neoplastic agent in managing MPE in NSCLC. Methods: We searched PubMed, Scopus, CENTRAL, ASCO, ESMO, and IASLC meetings libraries to retrieve relevant trials. We included single-arm and controlled trials in which patients with MPE were treated by anti-neoplastic drugs such as chemotherapy and/or targeted therapy. Patients treated with radiotherapy were excluded. Primary and secondary endpoints were efficacy and safety, respectively. Meta-analysis was conducted for the primary endpoint estimated by OS and objective response rate (ORR). In addition, subgroup analysis was conducted to investigate the effect of route of administration (ROA) and randomization on ORR. Results: We included 11 trials with a total of 542 patients. There were 5 randomized clinical trials, 5 phase II trials, and 1 phase I trial with a total of 16 relevant arms. Five arms used single-agent chemotherapy (SC), 11 combined therapy (CT) and 6 arms bevacizumab-based (BEVA) therapy. The ROA was intrapleural (IP) in 10 arms and intravenous (IV) in 6 arms. We pooled 124 patients from 5 trials that reported ORR results for SC patients. The pooled ORR was 41.7% (95% CI: 32.8 to 50.8%) with no heterogeneity ( I2 = 0%, p = 0.47). Pooling of 396 patients who underwent CT in 10 studies results in an ORR of 64.1% (95% CI: 52.7 to 74.8%) with a high heterogeneity rate ( I2 = 84%, p&lt; 0.01). Analysis of BEVA studies yielded an ORR of 62.2% (95% CI: 43.5 to 79.2%), representing 133 patients from 5 trials. The table shows the effect of randomization and ROA on ORR. One-year OS was reported in 4 studies that used CT; pooled 1-year OS estimate for 216 patients was 81.2% (95% CI: 75.5 to 86.4%). As for grade 3/4 AEs, the occurrence of nausea/vomiting (N/V) was higher in CT than SC (14% vs 2%). Chest pain rate was similar (9.8% vs 7.0%), leukopenia was higher in BEVA than SC (19.1% vs 9.8%), and neutropenia was more prevalent in BEVA than CT (22.1% vs 8.1%). Incidence of any-grade N/V was more common in BEVA than SC (42.9% vs 19.3%). Conclusions: Both CT and BEVA-based regimens were effective and safe in treating MPE. IP was superior to IV in CC and BEVA based regimens. ORR was higher in randomized trials, suggesting a better response of MPE under optimum clinical conditions. Further trials of these agents are needed to confirm these results.[Table: see text]

Dental Evaluation Prior to Cancer Therapy.

A comprehensive oral examination and dental care prior to the start of cancer therapy is the standard of care in many cancer centers. This is because good oral health will likely minimize the undesirable complications such as opportunistic infections during cancer therapy. As the considerations differ between anti-neoplastic regimens, this chapter discusses the indications and rationale when planning and executing a treatment plan for patients undergoing various cancer therapies.

Hyperpigmented Scleroderma-like Lesions under Combined Pembrolizumab and Pemetrexed Treatment of Non-Small Lung Cancer

Immune checkpoint inhibitors (ICI) and other antineoplastic treatment regimens can trigger cutaneous immune-related adverse events (irAEs). There is a tendency for underreporting of such cases, as cutaneous irAEs are typically perceived as mild and transient. However, more serious cutaneous irAEs can occur which, despite their lower frequency, deserve attention and require specific care. Here, we report a case of extensive hyperpigmented scleroderma-like lesions (SLL) on the lower extremities under combination treatment with pembrolizumab and pemetrexed in a patient with metastatic non-small cell lung cancer. The present case in conjunction with a review of the current literature underscores the potential risk of developing SLL under treatment with anti-PD-1 antibody and/or pemetrexed. Moreover, it is possible that this particular combination treatment synergistically increases the risk of SLL. As a result, more such cases may arise in the future, as ICI/pemetrexed combination treatment might be employed more often. As drug-induced SLL usually require systemic treatment with high dose-corticosteroids, physicians should be aware of SLL as an irAE when cancer patients present with sclerotic and/or fibrotic skin lesions.

COVID-19 (SARS-CoV-2 infection) in lymphoma patients: A review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection now has a global resonance and represents a major threat for several patient populations. Observations from initial case series suggested that cancer patients in general might have an unfavorable outcome following coronavirus disease 2019 (COVID-19), due to their underlying conditions and cytotoxic treatments. More recently, data regarding the incidence and clinical evolution of COVID-19 in lymphomas have been reported with the aim to identify those more frequently associated with severe complications and death. Patients with lymphoma appear particularly vulnerable to SARS-CoV-2 infection, only partly because of the detrimental effects of the anti-neoplastic regimens (chemotherapy, pathway inhibitors, monoclonal antibodies) on the immune system. Here, we systematically reviewed the current literature on COVID-19 in adult patients with lymphoma, with particular emphasis on disease course and prognostic factors. We also highlighted the potential differences in COVID-19 clinical picture according to lymphoma subtype, delivered treatment for the hematological disease and its relationship on how these patients have been managed thus far.

COVID-19 infection in pediatric patients treated for cancer.

BackgroundCOVID-19, the novel coronavirus, has caused a global pandemic affecting millions of people around the world. Risk factors for critical disease in adults are advanced age and underlying medical comorbidities, including cancer. Data are sparse on the effect of COVID-19 infection on pediatric patients with cancer during their active antineoplastic therapy. The optimal management of antineoplastic treatment during COVID-19 infection in this unique population is controversial.AimTo describe the severity and clinical course of COVID-19 infection in pediatric patients with cancer during active antineoplastic treatment and to study their course of treatment.MethodsClinical and laboratory data were collected from medical files of patients diagnosed with COVID-19, confirmed by polymerase chain reaction (PCR), who received active antineoplastic treatment between March 2020 and May 2021 in a large tertiary pediatric medical center.ResultsEighteen patients with diverse pediatric cancers are described. They were infected with COVID-19 at different stages of their antineoplastic treatment regimen. Eight had an asymptomatic COVID-19 infection, nine had mild symptoms, and one had severe disease. All of them recovered from COVID-19 infection. Two patients experienced delays in their antineoplastic treatment; none of the other patients had delays or interruptions, including patients who were symptomatic for COVID-19.ConclusionIn pediatric patients with cancer who test positive for COVID-19, yet are asymptomatic or have mild symptoms, the continuance of antineoplastic therapy may be considered.

Role of Cardioprotective Medications in Patients with Reduced Global Longitudinal Strain Undergoing Autologous Hematopoietic Stem Cell Transplant to Prevent Post-Transplant Cardiac Morbidity

Background: Cardiotoxicity is one of the side effects of many antineoplastic treatments. Establishing a baseline cardiac function prior to initiating therapy is of paramount importance and may be the limiting factor to choose a certain antineoplastic treatment regimen. Echocardiographic strain techniques including Global Longitudinal Strain (GLS) measurements are sensitive for detecting preclinical cardiac dysfunction and is a predictor for future reduction in ejection fraction and long-term outcome. Autologous transplant is performed as a consolidation strategy for many hematological malignancies and patients who undergo transplant are treated with high doses of chemotherapy including alkylating agents, which can affect cardiac function along with the strain of pancytopenia. Literature that describes the effects of transplant on cardiac function in patients who have reduced Global Longitudinal Strain is scarce if any at all. Most of the data for low GLS in patients receiving cardiotoxic medications suggest poor long-term morbidity and mortality.Objective and design: We present a case series of 3 patients diagnosed with multiple myeloma undergoing an autologous stem cell transplant as part of their treatment with reduced global longitudinal strain on pre-transplant assessment. These patients were treated with cardioprotective medications (Beta Blockers and/or ACEi/ARBs) before and while undergoing conditioning chemotherapy and subsequently autologous stem cell transplant and were followed until day 100.Results: Follow up in the post-transplant period showed improvement of GLS with and none of these patients demonstrated any signs or symptoms of cardiovascular morbidity.Conclusion: Reduced GLS should therapy in patients undergoing ASCT and cardioprotective medications may have a role in reducing cardiac morbidity and mortality in these patients. Our patients displayed improved GLS in the post-transplant period suggesting the need for further research and streamlining the role of cardio-oncology and cardioprotective treatment in similar situations. [Display omitted] DisclosuresRaval: Abbvie Pharmaceuticals: Speakers Bureau; Adaptive Biotechnologies: Consultancy; ADCT Therapeutics: Consultancy, Speakers Bureau; Alexion Pharmaceuticals: Speakers Bureau; Amgen Biotechnology Company: Research Funding; Astellas Pharmaceuticals: Speakers Bureau; Astrazeneca Pharmaceuticals: Consultancy, Speakers Bureau; Beigene Pharmaceuticals: Speakers Bureau; Bristol Meyers Squibb Pharmaceuticals: Consultancy; Epizyme Pharmaceuticals: Consultancy, Speakers Bureau; Genetech Biotechnology Company: Research Funding; GlaxoSmithKline Pharmaceuticals: Consultancy; Incyte Pharmaceuticals Corporation: Speakers Bureau; Jazz Pharmaceuticals: Consultancy; Karyopharm Therapeutics: Consultancy; Morphosys Biotech Company: Speakers Bureau; Sanofi Genzyme: Consultancy; Seagen Biotechnology Company: Research Funding; Takeda Pharmaceuticals: Consultancy, Speakers Bureau.

Pembrolizumab in endometrial cancer: Where we stand now.

Recently, immunotherapy has shown promising results in solid tumors. To the best of our knowledge, this is the first systematic review of published literature synthesizing all the available data and evaluating both the efficacy and safety of pembrolizumab in endometrial cancer. The present study was performed in accordance with the PRISMA guidelines. Eligible articles were identified by searching the MEDLINE and ClinicalTrials.gov databases, using a predefined combination of the terms ‘endometrial cancer’ and ‘pembrolizumab’. Overall, nine articles incorporating data from 712 patients were eligible. Pembrolizumab was demonstrated to be an effective and safe therapeutic option for the management of advanced/metastatic endometrial cancer. Results of ongoing trials evaluating either pembrolizumab alone or in combination with other antineoplastic regimens are expected to confirm its efficacy in this setting of patients. Pembrolizumab appears to be both durable and robust in endometrial cancer. However, there is an emerging need for novel predictive biomarkers to guide clinical practice.

Chemotherapy roadmaps in pediatric oncology: A digital electronic medical record integrated solution.

Delivery of antineoplastic regimens in the pediatric setting is facilitated by a paper roadmap. Paper roadmaps are the key safety tool required for safe ordering. Electronic medical record systems offer technological solutions for ordering antineoplastic regimens, however, do not offer a solution that integrates paper roadmaps digitally. A multidisciplinary project team implemented real-time clinician scanning of paper roadmaps into the electronic medical record. The rate of missing roadmaps decreased from an average of 1.6 to 0.8 per week. Pharmacists gained 3 h of productivity daily. Providers spend an average of 35-45 s and a total of seven clicks each time a roadmap is scanned. Overall, the clinical systems analyst spent less than 1 h of total build time. Implementing roadmap scanning decreased the rate of missing roadmaps, increased pharmacist productivity, and required a nominal amount of analyst and provider time. In addition, this solution allows for concurrent viewing of the roadmap files from any connected computer, facilitating an easier co-signature process for providers, pharmacists, and nurses. These results suggest that implementing real-time scanning of roadmaps can improve oncology care efficiency while maintaining the same safety rigor that paper roadmaps offer.

REVIEW ON THE SIGNIFICANCE OF QUINAZOLINE DERIVATIVES AS BROAD SPECTRUM ANTI-CANCER AGENTS.

Cancer is one of the major causes of human mortality worldwide. A number of approved antineoplastic medications and treatment regimens are already working in the field, and several new compounds are in different phases of clinical trials. An extensive series of anticancer drugs exist in the market, and studies explained that these molecules are associated with different types of adverse side effects. The reduction of the cytotoxicity of drugs to normal cells is a major problem in anticancer therapy. Therefore, researchers around the globe are involved in the development of more efficient and safer anticancer drugs. An interesting output of extensive research is that the quinazoline scaffold and its various derivatives can be explored further as a significant class of cancer chemotherapeutic agents that has already shown promising activities against different tumors. In general, quinazoline derivatives have already occupied a crucial place in modern medicinal chemistry. Quinazoline is one of the most studied moieties in medicinal chemistry due to the wide range of biological properties such as the anticancer, antibacterial, anti-inflammatory, antimalarial and antihypertensive activities. The anticancer activity of this scaffold has been well established.

Drivers of Treatment Patterns in Patients with Chronic Lymphocytic Leukemia (CLL) Treated with B-Cell Receptor Inhibitors (BCRis) — a Medical Chart Review Study

Drivers of Treatment Patterns in Patients with Chronic Lymphocytic Leukemia (CLL) Treated with B-Cell Receptor Inhibitors (BCRis) — a Medical Chart Review Study

Early Cardiovascular Toxicity with Treatment of Follicular Lymphoma Is Associated with Shorter Overall Survival

Introduction: The clinical course of follicular lymphoma (FL) is characterized by recurrent relapses and progressively shorter remissions, with many patients surviving beyond one decade from initial diagnosis. During this time, patients will receive several courses of therapy, which can be complicated by significant toxicities, particularly in elderly patients with multiple comorbidities. While the incidence and outcomes of cardiovascular toxicities observed in subjects with aggressive lymphomas treated with anthracycline based chemotherapy are well known, there is limited information regarding the incidence of cardiovascular events (CVE) in FL patients, many of whom have historically received similar antineoplastic regimens. We conducted a retrospective study to observe the incidence of CVE in FL patients from the time of diagnosis and their effect on patient outcomes.Patients and Methods: We accessed the Hematologic Malignancies Database of University Hospitals Seidman Cancer Center to identify patients diagnosed with FL between 2002 and 2014. We collected patient data including baseline demographics and risk factors, disease characteristics, treatments prescribed and outcomes, including response, relapse, and incidence of CVE. Multivariate logistic regression modeling was performed to identify risk factors associated with incidence of CVE. Cumulative incidence (with death as competing risk) was used to estimate the incidence of CVE. The Kaplan-Meier method was used to assess overall survival (OS) and progression-free survival (PFS). Two-tailed log-rank test compared OS and PFS curves. All analyses were performed using IBM SPSS Statistics 2015.Results: Two hundred and twenty-seven FL patients were included for analysis. Median age at diagnosis was 60 years, with 161 patients presenting with advanced stage FL (71%). Approximately two thirds of patients had intermediate or high-risk disease by FLIPI at diagnosis (n= 147, 65%). Decreased ejection fraction at diagnosis was identified in 5 patients (2.2%). Baseline characteristics and initial therapy choice are summarized in Table 1. A total of 143 patients (63%) received chemo-immunotherapy as part of their initial therapy, which included an anthracycline in 99 subjects (44%).After a median follow up of 66 months, 52 patients (23%) have died. Forty-two patients (18.5%) presented with CVE, with 2 and 5 - year cumulative incidence of 6.4 % (95% CI, 3.9-10.6%) and 13.5% (95% CI, 9.5-19.2%) respectively. Twenty- three patients (10%) developed congestive heart failure while 9 (4%) had an acute coronary syndrome or required coronary artery disease revascularization. Multivariate analysis (Table 2) identified age > 60 years, male gender, prior history of coronary artery disease and anthracycline treatment were independent risk factors for CVE.Patients who were prescribed systemic or local therapy after initial diagnosis of FL had a higher cumulative incidence of CVE than patients who were observed initially (5-year cumulative incidence 15.8% vs 9.6 %, respectively) (p=0.043). In addition, subjects who received anthracycline-based therapy at any point in the treatment course presented a higher cumulative incidence of CVE than those never treated with anthracyclines (5-year cumulative incidence 19.1% vs 8.2%, respectively) (p=0.019). The 5-year OS of patients who developed a CVE within 2 years of diagnosis was 56% (95% CI, 27.3-85.6%) versus 85% (95% CI, 80.1-90.3%) in patients who did not develop an early CVE (p=0.048) (Figure 1)Conclusion: Cardiovascular events in patients diagnosed with FL have a significant effect on their OS. Patients who require treatment are at increased risk of developing cardiovascular events, particularly those treated with anthracycline-based chemo-immunotherapy. Continued investigation is necessary to determine whether novel therapies have the same effect in cardiovascular risk. Interventions to identify, monitor and ameliorate cardiovascular risk factors in patients with FL should be investigated to improve survival. [Display omitted] DisclosuresMalek:Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees; Celgene: Speakers Bureau. Cooper:Novartis: Research Funding. de Lima:Celgene Corporation: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees. Caimi:Abbvie: Equity Ownership; Incyte: Equity Ownership; Celgene: Speakers Bureau; Seattle Genetics: Equity Ownership.

Patient and caregiver experience with an online, open-access, standardized, evidence-based, cancer drug and supportive care educational platform.

e18811 Background: An open-access, web-based platform was developed to provide standardized, evidence-based information, that is cancer regimen-specific and supportive care focused. Online content was provided in the English language only for more than 200 anti-neoplastic regimens. A survey was conducted to determine reasons adult patients and their caregivers seek internet-based cancer drug information, and to evaluate if there is an unmet need for improved oncology therapy education. Methods: Between February 2020 and January 2021, patients and caregivers completed an online anonymous, English language survey deployed on the website www.chemoexperts.com. Results: A total of 1,021 website users responded. The majority of users were from North America (75%). Female respondents comprised 65% of the population and users self-identified as being a patient (67%), or family member/caregiver (33%). The mean age of respondents was 60.7 years (+ 16.2). Roughly two-thirds (66.4%) had a college degree. The majority of respondents reported they were either currently receiving (59.6%), or planning to receive (27.4%) treatment, however patients of all education levels, and in all phases of treatment (before, during, and after) sought online drug information. Clinical drug information education was reportedly provided by a doctor (68.9%), nurse (40.9%), physician assistant or nurse practitioner (23.8%), or pharmacist (15%), while 23% did not receive any education from clinical staff. Modes of education received by participants included printed material (73.9%), teaching in person (52.3%), and/or other internet sites (27.5%). Reasons for visiting the website were reported as follows: seeking additional information (92%), did not know what questions to ask (12%), looking at treatment alternatives (10%), forgot to ask questions (5%), not enough information given (11%), not enough time to ask questions (5%), and afraid to ask questions (2%). Respondents could mark all reasons. Among content sections, the percentage of users reported the side effect section as being the most useful. However, section usefulness varied based upon age, phase of treatment, and baseline education level. Overall, 86% reported finding the information they were looking for on the website. Conclusions: The majority of respondents received education from a health care provider, but not all. It is possible that the current pandemic prevented some patients from receiving education when in-person teaching was not available. However, many patients and caregivers still use the internet to seek additional drug information. These data highlight a continued unmet need for patients using online sources when searching for cancer drug and supportive care information. Further work is required to determine whether supplemental online, education can improve outcomes while reducing adverse effects.

Treatment Decisions for Patients with Cancer during the COVID-19 Pandemic.

Patients with cancer have been disproportionally affected by the COVID-19 pandemic, with high rates of severe outcomes and death. Similarly, treatment decisions in this vulnerable population have been altered to a major degree during the past year, with significant disruption of care reported. Although complex, therapeutic choices in patients with cancer in times of COVID-19 are critical, as they may save thousands of lives. A mounting body of evidence, in addition to clear recommendations by multiple international societies, can help oncologists decide appropriately the necessity to administer antineoplastic regimens, helping to avoid a surge in cancer-related deaths in the upcoming months.

Using betaxolol for the prevention of paronychia induced by epidermal growth factor receptor inhibitors: a case-control cohort study.

High rates of posttreatment discomfort, infection, recurrence, and increased time to return to work have been noted after nail plate avulsion resulting from epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)-induced paronychia, which may even interrupt the course of treatment for EGFR-TKI therapy. Thus, we conducted this study to determine how effectively a topical β-blocker, betaxolol, prevents EGFR-TKI-induced paronychia. This case-control cohort study included a total of 131 non-small-cell lung cancer patients. The prevention group comprised 40 patients treated with topical betaxolol 0.25% solution to prevent paronychia while they received EGFR-TKI therapy. The control group comprised 91 patients who did not preventively use topical betaxolol 0.25% solution while receiving EGFR-TKI therapy. The patients' age, gender, antineoplastic regimen, duration of antineoplastic treatment before the appearance of lesions, number of involved digits (fingernails or toenails) with lesions, grading of paronychia, and pain score were recorded. In terms of the cumulative incidence of paronychia, significant differences (P<0.01) were noted at both the 2nd and 3rd months after starting EGFR-TKIs. Furthermore, the average visual analogue scale scores were 3.125 and 6.29 in the prevention group and control group, respectively (P<0.01). The average grades of paronychia were 1.5 and 2.12 in the prevention group and control group, respectively (P<0.01). The average numbers of involved digits were 2.25 (range: 1-5 digits) in the prevention group and 3.03 (range: 1-7) in the control group (P=0.07). Preventively using topical betaxolol can significantly decrease the incidence, VAS score, and grading of EGFR-TKI-induced paronychia.

Immune Dysfunction and Multiple Treatment Modalities for the SARS-CoV-2 Pandemic: Races of Uncontrolled Running Sweat?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic threat with more than 11.8 million confirmed cases and more than 0.5 million deaths as of 3 July 2020. Given the lack of definitive pharmaceutical interventions against SARS-CoV-2, multiple therapeutic strategies and personal protective applications are being used to reduce the risk of high mortality and community spread of this infection. Currently, more than a hundred vaccines and/or alternative therapeutic regimens are in clinical trials, and some of them have shown promising results in improving the immune cell environment and controlling the infection. In this review, we discussed high-performance multi-directory strategies describing the uncontrolled deregulation of the host immune landscape associated with coronavirus disease (COVID-19) and treatment strategies using an anti-neoplastic regimen. We also followed selected current treatment plans and the most important on-going clinical trials and their respective outcomes for blocking SARS-CoV-2 pathogenesis through regenerative medicine, such as stem cell therapy, chimeric antigen receptors, natural killer (NK) cells, extracellular vesicular-based therapy, and others including immunomodulatory regimens, anti-neoplastic therapy, and current clinical vaccine therapy.

Abstract 5025: Antifungal ketoconazole inhibits tumor-specific transcription factor tGLI1 leading to suppression of breast cancer stem cells and brain metastasis

Abstract Breast cancer is the second leading cause of brain metastases in women; patients with breast cancer brain metastasis (BCBM) survive only 6-18 months following diagnosis. Current standard of care options for BCBM include stereotactic radiosurgery, whole-brain radiotherapy, and surgical resection. Cancer stem cells are thought to be one of the driving forces behind not only distant metastasis, but also late-stage recurrence. The hedgehog pathway has been identified as an important mediator of stem cells, however, FDA-approved therapies targeting this pathway have demonstrated limited efficacy in breast cancer clinical trials. Despite our current knowledge of breast cancer stem cells (BCSC), there remains a significant challenge in managing patients with metastatic breast cancer, underscoring the need to identify novel, actionable targets. Our laboratory discovered an alternative splice variant of glioma-associated oncogene homolog 1 (GLI1), termed truncated GLI1 (tGLI1), that is a tumor-specific gain-of-function transcription factor and terminal effector of the hedgehog pathway that is preferentially expressed in most BCBM samples and recurrent gliomas. Recent results established that tGLI1 promotes BCSC and is associated with preferential metastasis to the brain and radioresistance, justifying tGLI1 as an ideal therapeutic target for BCBM patients. To identify tGLI1-targeting agents, we screened 1,520 compounds across three commercial drug libraries and found ketoconazole (KCZ), an FDA-approved imidazole antifungal and component of previously studied anti-neoplastic regimens, selectively killed tGLI1-expressing breast cancer cells with increased efficacy against BCSC in vitro. tGLI1 knockdown abolished the ability of KCZ to target BCSC, indicating that KCZ-mediated suppression of BCSC is dependent on tGLI1. Intracardiac mouse studies showed KCZ selectively inhibited circulating tGLI1-positive breast cancer cells from developing into brain metastases and suppressed the progression of existing brain metastases. Mass spectrometry demonstrated KCZ effectively penetrated the blood-brain barrier (BBB) and blood-tumor barrier (BTB). Mechanistic studies suggest that KCZ-dependent cell kill is, in part, mediated through disruption of the functional tGLI1-STAT3 interaction. Furthermore, modification of KCZ side chains produced derivative compounds that retained tGLI1-selectivity in both in vitro models of BCSC and in vivo models of BCBM with increased BBB penetrance. Collectively, our preclinical results demonstrate that KCZ is an effective inhibitor of BCSC and brain metastasis of tGLI1-positive breast cancer. Based on these promising preclinical data, we opened a window-of-opportunity study in patients with BCBM and recurrent gliomas to determine if KCZ treatment alters tGLI1 signaling in humans (NCT03796273). Citation Format: Daniel L. Doheny, Sherona R. Sirkisoon, Tadas Rimkus, Dongqin Zhu, Noah R. Aguayo, Alexandria Harrison, Marlyn Anguelov, Sara Manore, Fei Xing, Linda J. Metheny-Barlow, Kounosuke Watabe, Alexandra Thomas, Adrianna Henson Masters, Roy Strowd, Hui-Wen Lo. Antifungal ketoconazole inhibits tumor-specific transcription factor tGLI1 leading to suppression of breast cancer stem cells and brain metastasis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5025.