bluuebunny/crossref_metadata_2025 huggingface dataset:
The influence of EGFR mutation status and PD-L1 expression in stage III unresectable non-small cell lung cancer treated with chemoradiation and consolidation durvalumab.
Authors: Nindra Udit , Stevens Samuel Xavier , Shahnam Adel , Pal Abhijit , Adam Tamiem , Yip Po Yee , Lee Jenny HJ , Boyer Michael J. , Nagrial Adnan , Kao Steven Chuan-Hao , Bray Victoria Jane
Published: June 2022

e18810

Background: The PACIFIC trial established concurrent chemoradiation followed by one year of consolidation durvalumab as the standard of care for unresectable stage III non-small cell lung cancer (NSCLC). However, the data to support the use of durvalumab in patients with EGFR mutations and low PD-L1 expression is less clear. This study adds to the available evidence by describing the survival outcomes for patients with stage III unresectable NSCLC treated with chemoradiation followed by durvalumab with a focus on their EGFR mutation and PD-L1 status. Methods: This retrospective observational study was conducted at six sites across Sydney, Australia. It included patients diagnosed with unresectable stage III NSCLC treated with chemoradiation and at least one cycle of durvalumab between January 2018 to September 2021. Patients were stratified into EGFR wild-type and mutated tumours and PD-L1 tumour proportional score (TPS) greater than or less than 1%. Survival analyses were supplemented with cox proportional hazards regression models which estimated HRs for PFS in treatment group comparisons. The proportional hazards assumption was confirmed for all cox models. All statistical analysis was done using R version 4.1.1. Results: 146 patients were included in the analysis. The median follow-up from the start of Durvalumab was 15.1 months. The median age was 66 years in the EGFR mutated and 65 years in the EGFR wild-type cohorts. 61% (n = 89) of patients were male. 10% (n = 15) of patients had EGFR mutation. 42% (n = 61) of patients had a PD-L1 TPS of < 1%. PD-L1 expression was similar in both cohorts with 47% (n = 7) of EGFR mutated patients having PD-L1 TPS of < 1% compared with 45% (n = 59) in the wild-type group. The median progression-free survival (PFS) was 7.5 months for EGFR mutated patients versus 33.9 months for EGFR wild- type patients (HR: 2.7; 95% CI: 1.2 – 5.7; p = 0.01). There was no statistically significant difference in either PFS (HR 0.7, 95% CI 0.4 – 1.7, p = 0.43) or OS (HR 0.5, 95% CI 0.4 – 4.7, p = 0.16) for patients with PD-L1 TPS of < 1% compared with PD-L1 TPS of > 1%. Conclusions: Our data adds to the growing evidence that suggests consolidation durvalumab after definitive chemoradiation may not be as efficacious in patients with EGFR-mutated tumours. PD-L1 TPS did not affect survival outcomes.
Burden of insomnia among cancer patients undergoing treatment: A retrospective claims database analysis.
Authors: Wickwire Emerson M , Juday Timothy R , Frech Feride H , Kelkar Mona Arti , Heo Jihaeng , Malhotra Manoj
Published: June 2022

e18816

Background: Almost half of all cancer patients have trouble sleeping, usually insomnia or other sleep-wake disorders. Cancer treatment can exacerbate sleep problems. This study evaluated all-cause healthcare resource utilization (HCRU) and costs in cancer patients undergoing treatment who also have insomnia relative to a matched cohort of cancer patients undergoing treatment who do not have insomnia. Methods: This retrospective study used the IBM MarketScan Commercial and Medicare Supplemental Databases (Jan 2014-Dec 2019) to identify patients: (1) age ≥18 years; (2) with ≥1 ICD-9/ICD-10 codes for insomnia OR with ≥2 prescriptions for zolpidem immediate release (IR) OR trazodone ≤150mg OR benzodiazepine; (3) with ≥12 months of continuous enrollment pre-/post-index date (earliest diagnosis or medication fill date); (4) with ≥2 ICD-9/ICD-10 codes for any cancer; and (5) ≥1 claim for oncology treatment. Patients with sleep disorders other than insomnia were excluded. The resulting patients (“insomnia cohort”) were 1:1 matched on age, sex and Elixhauser Comorbidity Index (ECI) score to patients with cancer undergoing treatment without insomnia or other sleep disorders (“control cohort”). HCRU and costs were reported per patient per month (PPPM). Generalized linear models were used to compare adjusted outcomes between cohorts. Results: For each cohort, 7,132 patients (mean age 60.8 years, 69.5% female, 13.6 ECI score) were identified. In adjusted analyses, significantly more patients in the insomnia cohort had at least one inpatient visit per month, inpatient stays were significantly longer, and mean outpatient visits were significantly higher (all p < 0.001) relative to the control cohort. The insomnia cohort had higher mean number of emergency department (ED) visits (p < 0.05); however, mean number of inpatient visits was not significantly different between cohorts. Adjusted analyses also showed significantly higher mean total PPPM costs for the insomnia cohort than the control cohort ($4,864 and $3,302, respectively; mean ratio = 1.47; p < 0.0001). Mean PPPM costs for inpatient visits, ED visits, and outpatient costs were also higher for the insomnia cohort (p < 0.001). Conclusions: Cancer patients undergoing treatment who have insomnia had more intensive HCRU and higher costs relative to those without insomnia. These results suggest that better managing insomnia in this population may have a beneficial impact on both patients and payers.
Application of value framework to phase III trials of immune checkpoint inhibitors in esophageal and gastric cancer.
Authors: Thawani Rajat , Agrawal Neha , Taflin Nicholas , Kardosh Adel , Chen Emerson Yu-sheng
Published: June 2022

e18817

Background: Recent clinical trials testing use of immune-checkpoint inhibitors in esophageal and gastric carcinomas have shown both positive and negative results. Given these mixed signals, we aimed to assess outcomes and tolerability of key subgroups using the ASCO Net Health Benefit Score (NHBS) and ESMO Magnitude of Clinical Benefit Scale (MCBS). Methods: A detailed search for phase III trials investigating use of FDA-approved anti PD-1 or anti PD-L1 drugs in esophageal and gastric cancer trials was completed using www.clinicaltrials.gov followed by primary literature identification on PubMed. These studies were then independently selected, reviewed, and scored using the ASCO NHBS and ESMO MCBS by two investigators, and any discrepancy was mutually resolved. The ASCO NGBS scores were compared by primary site of cancer (esophageal vs gastric) and PD-L1 expression using the Mann-Whitney test. The ESMO-MCBS grading were compared using Fisher's Exact test. Results: Of the 45 records identified, 15 clinical trials were included. Of them, six were primarily esophageal cancer trials, and nine were primarily gastric cancer trials. Of all 15, 10 stratified their analysis based on PD-L1 expression. The ASCO NHBS score was significantly higher for esophageal cancer than gastric cancer (mean 40, range 20  56.6 vs. mean 12, range -1.1  18.4, p < .01). No difference, however, was observed in survival and response rate outcome endpoints between the two groups. Similarly, the ESMO MCBS was also higher for esophageal cancer group than gastric cancer (p < .05). Additionally, the median scores were higher in the patients with high PD-L1 expression vs low PD-L1 expression (mean 37, range 11.2  66.6 vs. mean 14, range -19.5  43.6, p < .05). Conclusions: In this cohort of drug registration trials of immune checkpoint inhibitors for upper GI cancers, we showed the ASCO NHB scores and ESMO scores were consistently higher among esophageal cancer trials than gastric cancer trials and in those with high PD-L1 expression than those with low PD-L1 expression. Oncologists should carefully discuss overall clinical value and expectations of immunotherapy benefit with their patients per cancer histology and PDL1 expression, exercising caution in cases of gastric adenocarcinoma with low PD-L1 expression.[Table: see text]
Remote patient monitoring (RPM) through smartphone application in community oncology practice.
Authors: Kuthiala Rayna , Telivala Bijoy Pankaj , Karawadia Tejas
Published: June 2022

e18828

Background: Patients with cancer receiving treatment can have symptoms related to their disease or treatment. Early recognition and appropriate intervention of these symptoms can lead to fewer emergency room visits and fewer hospitalizations with significant reduction in healthcare costs. Earlier treatment of symptoms leads to more adherence to treatment. We present data regarding reduction in healthcare costs after implementation of remote patient monitoring in our community oncology practice with 13 oncology practice sites and 29 medical oncologists in Jacksonville, Florida. Methods: We implemented RPM through a smartphone application at all our practice sites starting September 1,2021. We collected data regarding number of patients on active therapy who required inpatient admissions during the 3-month period from 9/1/2021 to 11/30/21 . We documented the number of admissions during this 3-month period in 2020, prior to implementation of RPM followed by number of admissions during the same period of time in 2021 after the implementation of RPM. The numerical difference in admissions was then multiplied by average cost of hospitalization for adult cancer patients to calculate the healthcare cost savings. Results: During the 3-month period in 2020 without RPM, there were 234 inpatient admissions. During the same time frame in 2021, after implementation of RPM, there were 199 admissions. The implementation of RPM, showed a 15 % reduction in number of inpatient admissions. Average cost of inpatient stay for a cancer patient is $22,100 as per the data from healthcare cost and utilization project. This would translate to $773,500 over 3-month period and approximately $3 million annual healthcare cost savings. The annual cost of implementation of RPM in our practice was $350,000 which includes cost of smartphone application and the required clinical staff. Conclusions: Remote patient monitoring through smartphone application can be effectively implemented in community oncology practice with significant reduction in healthcare costs. Not only does it save money, it helps improve patient experience and adherence to treatment. We will continue to collect data to see if the trend continues.
Total cost of care differences in National Comprehensive Cancer Center (NCCN) concordant and non-concordant breast cancer patients.
Authors: Sapkota Ujwal , Cavers William , Reddy Shirisha , Avalos-Reyes Elisea , Johnson Kjel Andrew
Published: June 2022

e18833

Background: National Comprehensive Cancer Network (NCCN) treatment guideline non-concordance for breast cancer treatment has higher total costs. However, a significant knowledge gap exists regarding which cost components increase in non-concordant therapies. The purpose of this study is to evaluate the total cost of care (TCOC) and cost components for breast cancer patients who received NCCNconcordant versus non-concordant therapies. Methods: This is a retrospective study of patients throughout the United States with breast cancer at a large national Medicaid, Medicare, and commercial insurer from January 1, 2019, to December 31, 2020. NCCN regimen concordance was identified from pharmacy and medical claims and defined as concordant if the entire prescribed treatment regimen matched an NCCNregimen (Level 1 and 2a); patients not receiving an NCCN recommended regimen were deemed to be non-concordant. TCOC and its cost components were contrasted on a matched population of concordant and non-concordant patients with a ratio of 2:1. To eliminate possible selection bias and differences in baseline characteristics that could affect cost, propensity scores were developed using logistic regression and used to match patients on age, comorbidity, socioeconomic status (SES) index and treatment type (chemotherapy and radiation). Results: A total of 315 patients with breast cancer were matched. Beginning with and including the first treatment and for up to 180 days after, the TCOC in the concordant group was significantly less across all lines of business (p < 0.05). A reduction of 25%, 28% and 43% (a difference of $5,872, $6,946 and $3,542) in TCOC per member per month (PMPM) was observed in commercial fully insured (CFI), commercial self-insured (CSI) and Medicare patients, respectively. Provider administered chemotherapy spend was also significantly lower (p < 0.05) in the concordant group, a reduction of 34%, 50% and 43% (a difference of $3,615, $6,788 and $1,879) in CFI, CSI and Medicare patients, respectively. Outpatient spend was 28% lower (a difference of $4,268, p = 0.08) in CFI patients and significantly lower (p < 0.05) with reductions of 29% and 40% ($5,396 and $1,988) in CSI and Medicare patients, respectively. There were no significant differences in Inpatient and Emergency Room spend across all lines of business (p > 0.05). Conclusions: In this study, there is a correlation between breast cancer patients on NCCN concordant therapies and a lower TCOC. The savings due to medical spend highlight the importance of evidence-based guidelines in treatment determinations. Further evaluation will be needed to determine cost changes in hospitalizations and emergency room visits.
Choosing Wisely Africa: Insights from the front-lines of clinical care.
Authors: Rubagumya Fidel , Makori Kevin , Borges Hirondina , Mwanzi Sitna Ali , Karim Safiya , Msadabwe Susan Citonje , Dharsee Nazima Jaffer , Mutebi Miriam Claire , Hopman Wilma M. , Vanderpuye Verna D. , Ka Sidy , Ndlovu Ntokozo , Hammad Nazik , Booth Christopher M.
Published: June 2022

e18835

Background: A multidisciplinary Task Force of African oncologists and patient representatives published the Choosing Wisely Africa (CWA) recommendations in 2020. These recommendations identified low-value, unnecessary, or harmful practices that are frequently used in Sub-Saharan Africa (SSA). We describe agreement and concordance with the recommendations from front-line oncologists across SSA. Methods: A self-administered electronic survey was distributed to members of the African Organization for Research & Training in Cancer and oncology groups within SSA using a hierarchical snowball method. The survey captured information about awareness of CWA, agreement with recommendations, and concordance with clinical practice. Descriptive statistics were used to summarize study results. Results: 49 individuals responded to the survey; 61% (30/49) were female and 59% (29/49) were clinical oncologists. Respondents represented 14 countries in SSA; 69% (34/49) practiced exclusively in the public system. Only 43% (21/49) were aware of the CWA list and 90% (44/49) agreed it would be helpful if the list was displayed in their clinic. There was generally high agreement (Table) with the recommendations (range 84-98%); highest agreement related to staging/defining treatment intent (98%). The proportion of oncologists who implemented these recommendations in routine practice was somewhat lower (range 68-100%). Lowest rates of concordance related to: use of shorter schedules of radiotherapy (68%). Conclusions: While most frontline SSA oncologists agree with CWA recommendations, efforts are needed to disseminate the list. Agreement with the recommendations is high but there are gaps in implementation in routine practice. Further work is required to understand barriers and enablers of implementation.[Table: see text]
Impact of the oral chemotherapy pharmacist on direct cost avoidance and cost savings of oral oncolytics at an integrated health system.
Authors: Nguyen Analia
Published: June 2022

e18839

Background: The impact of oncology pharmacists on patient care have been well-documented including enhanced medication safety and efficacy, increased medication adherence, improved provider and clinic burden, and increased patient and provider satisfaction. There is a scarcity of articles relating to pharmacists’ drug cost savings or cost avoidance of oncologic drugs in an oral chemotherapy management clinic within an integrated healthcare system. Cost savings and cost avoidance studies are needed to reinforce this practice and gain support and funding from hospital administration. Methods: This retrospective, observational study analyzed interventions made by oncology pharmacists in the Pharmacist-Managed Oral Chemotherapy Clinic at Kaiser Permanente San Diego and determine the direct drug cost savings and cost avoidance effects over one year. Cost savings and cost avoidance were calculated by comparing the costs of drug utilization if no interventions were implemented versus costs of drug saved from accepted interventions for dose reduction, dose delay, temporary dose hold, therapy discontinuation, therapy conversion, formulary alternative conversion, and brand to generic conversion. Secondary outcomes included the highest and average cost avoidance per intervention, intervention type, medication, medication class, and cancer type. Additionally, interventions that did not lead to direct drug cost savings such as adverse drug reaction management, drug interaction identification, and supportive care recommendation were also recorded. The secondary endpoint was oncologist satisfaction via a six-question satisfaction survey. All documented oncology pharmacist interventions that were made in the Oral Chemotherapy Clinic from January 1 to December 31, 2021 were reviewed for study inclusion. From a report generated monthly from the electronic health record (EHR), retrospective chart review was conducted to verify whether each cost-savings intervention was truly recommended by an oncology pharmacist and if the intervention was accepted by the treating oncologist. The Average Wholesale Price (AWP) of drugs listed on Lexicomp as of November 1, 2021 was used to calculate the drug cost savings and cost avoidance. During this period, there were no changes to practice and no increased efforts to identify interventions. Results: As of September 2021, 156 interventions were identified, with a total cost savings and cost avoidance of $2,245,856. Once all data have been collected for the remainder of 2021, descriptive statistics will be used to analyze and stratify the data as appropriate. Conclusions: Pharmacist interventions in the Oral Chemotherapy Clinic led to significant overall cost savings to the health care system. It is reasonable to expect that higher cost savings will be achieved as more oral chemotherapy agents are managed by pharmacists.
Mismatched donor transplantation with post-transplantation cyclophosphamide for advanced cutaneous T-cell lymphoma: A single-center experience.
Authors: Hughes Michael Sang , Sterling Cole Harris , Varadhan Ravi , Ambinder Richard F. , Jones Richard J. , Rozati Sima , Bolanos-Meade Javier , Luznik Leo , Ambinder Alexander Joseph , Wagner-Johnston Nina D. , Fuchs Ephraim Joseph
Published: June 2022

e19045

Background: Mismatched blood or marrow transplantation (BMT) using post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease (GvHD) prophylaxis has not been well-studied in CTCL. Methods: We analyzed all patients above 18 years old with relapsed/refractory CTCL undergoing mismatched alloBMT. Primary endpoints included disease-free survival (DFS) and overall survival (OS). Secondary endpoints included time to neutrophil and platelet recovery, GvHD outcomes, and day +30 and day +60 donor chimerism. Results: From 2003-2020, 8 patients with relapsed CTCL underwent mismatched related (n=7) or mismatched unrelated (n=1) BMT. Mean age was 50 years (range 30-62); median time from diagnosis was 2 years (range 1.3-11.4). All had received prior treatment for their disease; two (25%) had received immune checkpoint inhibitors. Four (50%) were in partial response and 4 (50%) were in complete remission prior to BMT. Six received bone marrow grafts. Two received mobilized peripheral blood. Five (62.5%) achieved full donor chimerism by day 30 after BMT; 6 (75%) had achieved full donor chimerism by day 60 after BMT. One patient failed to engraft. Mean time to neutrophil recovery was 17.3 days (range 17-45); mean time to platelet recovery was 28.4 days (range 11-69). Median DFS was 11.3 months (95% confidence interval 2.6 months-not reached). Median OS was not reached. One patient developed grade 1 acute GvHD, and 2 patients developed mild chronic GvHD. There were no instances of transplantation-related mortality (TRM). At 1 year post-BMT, 4 patients had relapsed (50%), and no patients had died. At 3 years post-BMT, 7 patients had relapsed (87.5%), and 1 patient had died (12.5%). Conclusions: In our preliminary retrospective study, partially mismatched BMT with PTCy-based GVHD prophylaxis for advanced-stage CTCL was associated with minimal GvHD, no TRM, and good long-term survival. Investigation into relapse reduction is warranted.[Table: see text]
Expression of CD47 and CALR in myeloproliferative neoplasms: Potential new therapeutical targets.
Authors: Rinaldi Ciro Roberto , Boasman Kristian , Simmonds Matthew
Published: June 2022

e19075

Background: Myeloproliferative neoplasms (MPN) are myeloid malignancies characterized by overproduction of mature blood cells, hyperplastic bone marrow and tendency to evolve into acute myeloid leukaemia. In solid tumours, calreticulin (CALR) overexpression produces a pro-phagocytic signal and is counteracted by concomitant expression of anti-phagocytic CD47, reflecting an apoptosis vs survival mechanism. Increases of both CALR and CD47 on the cell membrane have been observed in response to chemotherapy, however their role in myeloid malignancies is poorly understood. Methods: Investigate the expression and cellular localisation of CALR and CD47 in untreated and treated patients with essential thrombocythemia (ET), polycythemia vera (PV) myelofibrosis (MF), in comparison with healthy controls. Mononuclear cells were collected by Ficoll separation, from peripheral blood of 30 MPN (8 PV, 16 ET, 6 MF); 18 MPN patients received cyto-reductive therapies (Hydroxyurea, Anagrelide or Ruxolitinib); and 4 controls. Cells were fractionised into 4 compartments: membrane, cytoplasm, cytosol and nucleus. Proteins were extracted using TRIzol, with CALR and CD47 protein expression analysed by western blotting. Results: Total CALR and CD47 protein expression increased in MPN samples compared with controls (CALR- 7.9 vs 5.1; CD47- 2.7 vs 2.2 fold, respectively). CD47 showed higher expression of its overall protein on MPN cell membranes when compared with CALR (22% vs 13.9%). We observed a significant reduction of CALR expression in all MPN subtypes when patients were treated with cyto-reductive agents (ET- untreated 43.3% vs treated 2%, PV- 3.6% vs 2.2%, ET- 21% vs 11%). Interestingly we have observed a significant increase in CD47 cell membrane expression after treatment in MF and PV (CD47 in MF- untreated 11.8% vs treated 34.3%, PV-11.4% vs 35.9%), suggesting an anti-phagocytic effect induced by cytotoxic drugs. In ET cell membranes however, CD47 expression is reduced after cyto-reductive treatment (22% vs 16.6%), suggesting instead a prophagocytic effect. Conclusions: CD47, but not CALR, is overexpressed on the membrane of patients with MPN, suggesting a role for CD47 as a strong antiphagocytic signal responsible for immune survival in MPN. We observed a significant difference in CD47 expression across different MPN subtypes with a significant increase in CD47 expression in PV and MF but not ET. The use of anti-CD47 antibodies could represent a new strategy to enhance the treatment response in particular in PV and MF.
Characteristics of patients with hematologic malignancies without seroconversion post-COVID19 third vaccine dosing (3V): Real-world data from large midwestern healthcare system.
Authors: Hallmeyer Sigrun , Thompson Michael A. , Fitzpatrick Veronica , Liao Yunqi , Mullane Michael P. , Medlin Stephen Charles , Cleland Katherine , Rodriguez Tulio , Citronberg Robert , Weese James L.
Published: June 2022

e19513

Background: Patients (Pts) with hematologic malignancies (HM) are at greater risk of severe morbidity and mortality caused by COVID19 and show a lower response to the two-dose COVID19 mRNA vaccine series. The primary vaccine series now includes a third dose of the COVID19 vaccine (3V) for immunocompromised Pts. The objective of this study was to explore the characteristics of HM patients who had no change in SARS-CoV-2 spike protein titer levels post 3V (-/-) to gain a better understanding of the drivers of serostatus. Methods: This retrospective cohort study analyzed Pt data on SARS-CoV-2 spike IgG antibody titers pre- and post- 3V across the healthcare system. This study included 268 fully vaccinated HM Pts diagnosed with HM between October 31, 2019 and January 31, 2022 and had a negative serostatus prior to 3V. Post 3V titers were obtained 21 days after 3V. Demographics, association between characteristics and seroconversion status, and odds ratios were all assessed (table). Results: Pts with Non-Hodgkin lymphoma (NHL) had 6 times the odds of not seroconverting compared to multiple myeloma (MM) (CI 1.88 – 19.12, P = .0010). NHL also have about 14 times the odds of not seroconverting compared to Pts diagnosed with other HM conditions, which included: neoplasms of uncertain behavior and disorders of white blood cells (CI 1.72 – 112.44, P = .0021). 90% of seronegative Pts showed no spike IgG antibody reaction to 3V as indicated by pre- and post- 3V index values. Demographics, previous COVID19 infection, and vaccine type were not significantly associated with seroconversion. Conclusions: HM patients who are not seroconverting after 3V, suggest a prioritized population for continued increased behavioral precautions, additional vaccination efforts, including a fourth dose of an mRNA COVID19 vaccine, as well as passive immunity boosting through monoclonal and polyclonal antibodies.[Table: see text]
Safety and efficacy of allogeneic CAR-T cells in B-cell malignancies: A systematic review and meta-analysis.
Authors: Chattaraj Asmi , Rehman Mohammad Ebad Ur , Khan Israr , Franco Diana , Ibrahim Atif , Khanam Razwana , Tahir Nayha , Iqbal Qamar , Waqar Syed Hamza Bin , Pachika Pranali Santhoshini , Khan Rafiullah , Anwer Faiz
Published: June 2022

e19530

Background: Immunotherapy with chimeric antigen receptor T (CAR-T) cells has proven effective in recent trials for patients with B cell malignancies, who relapsed after stem cell transplantation. Genetically modified allogeneic CAR T-cells used in advanced B cell malignancy engage with multiple target allo-antigens along with CD19 and/or CD20, leading to elimination of malignant B cells resulting in a potent graft versus malignancy effect with avoidance of tumor escape. Some concerns regarding their use exist like life-threatening graft-versus-host disease (GVHD) and rapid clearance by the host immune system. This study summarises the efficacy and safety of allogeneic CAR-T therapy in B cell malignancies. Methods: A systematic literature search was conducted on PubMed, Embase, Cochrane and Clinicaltrials.gov from inception to Jan 26, 2022, using MeSH terms and keywords for B cell malignancies and CAR-T therapy. We also screened the data presented in various conferences and handpicked references from previous systematic reviews. Outcomes of interest were complete remission (CR), 1-year overall survival (OS), GVHD, cytokine release syndrome (CRS), and immune effector cell associated neurotoxicity (ICANS). Proportional outcomes were pooled using a random effects model (Freeman-Tukey double arcsine transformation) in OpenMetaAnalyst software. Results: The initial search retrieved 1247 articles. After excluding reviews, duplicates and non-relevant articles, we included data from 9 clinical trials (n = 146 patients). The most common malignancy was acute lymphoblastic leukemia (125 patients, 86%). The median age of patients ranged from 19 to 49 years. All patients received CD19 targeting therapy and the cell dose administered ranged from 0.4×10^6 to 5×10^8 cells/kg. CR was reported in 93 of 146 patients, with a pooled rate of 63% (95% CI 47.4 - 78.6%; I2 78.5%). The pooled 1-year OS was 57.3% (95% CI 30.8 - 82%; I2 79.2%). The pooled proportion of GVHD was 9.4% (95% CI 3.1- 15.6%; I2 47.6%). The pooled CRS and ICANS rates were 59.3% (95% CI 30.5 - 88.1%; I2 95.2%) and 15.4% (95% CI 4.6 - 26.3%; I2 72.7%), respectively. Conclusions: Allogeneic CAR-T therapy has demonstrated acceptable efficacy and safety in B cell malignancies, with CR being reported in about 60% of patients and GVHD in < 10% of patients. Although allogeneic CAR-T cells are showing promise, several trials are ongoing and we need longer follow up.[Table: see text]
Prognostic role of neutrophil-to-lymphocyte ratio in patients with diffuse large B-cell lymphoma.
Authors: Kushtova Luiza B. , Frantsiyants Elena M. , Bandovkina Valeria A. , Kozel Yuliya Yu. , Dmitrieva Viktoria V. , Kozyuk Olga V. , Snezhko Aleksandr V. , Malinin Sergey A. , Chalkhakhyan Lusegen Kh. , Kaminskiy Gennadiy V. , Duritskiy Maksim N. , Gabrichidze Petr N. , Vladimirova Liubov Yu , Lysenko Irina B. , Nikolaeva Nadezhda V. , Kit Oleg I.
Published: June 2022

e19560

Background: Diffuse large B-cell lymphoma (DLBCL) represents about 30-40% of all cases of non-Hodgkin lymphoma. The addition of rituximab to standard chemotherapy significantly improves survival, yet 30% of advanced-stage patients relapse. The International Prognostic Index (IPI) is used to evaluate the prognosis, but it cannot always accurately predict the outcome of therapy. The neutrophil-to-lymphocyte ratio (NLR) has recently been recognized as a prognostic factor in various types of solid tumors. The purpose of this study was to assess the prognostic value of NLR in DLBCL patients. Methods: Patients with DLBCL (n = 47) were recruited, including 31 patients in remission and 16 patients with relapsed DLBCL. All patients received 6-8 cycles of R-CHOP. Clinical parameters were studied, including IPI and complete blood count before treatment and after each chemotherapy cycle. Results: IPI predicted unfavorable outcome in 3 (18.75%) patients with relapses, and favorable outcome and high treatment efficacy in 13 (81.25%) patients. Among patients in remission, IPI predicted unfavorable outcome in 2 (6.5%) patients and favorable outcome in 29 (93.5%) patients. NLR calculation showed 100% low treatment efficacy for patients with relapses (NLR =4.1±0.51). At the same time, NLR predicted favorable outcome in 22 (70.96%) patients in remission (NLR =1.9±0.20), and relapses in 9 (29.04%) patients (NLR =4.83±0.55). 7 (22.6%) of the patients at risk developed relapses within 6-10 months after good treatment effects. Conclusions: Thus, NLR can be used as a prognostic factor in patients with DLBCL.
Tisagenlecleucel in the treatment of aggressive large B-cell lymphoma: A review of literature.
Authors: Devarkonda Vishal , Balmuri Shravya , Ponna Pramod Kumar , Devarashetty Sindhu Priya
Published: June 2022

e19563

Background: Tisagenlecleucel is an anti-CD19 chimeric antigen receptor T-cell therapy approved for refractory diffuse large B-cell lymphoma(DLBCL) in May 2018. However, a recently concluded phase 3 international trial showed that Tisagenlecleucel was not superior to standard salvage therapy with aggressive lymphoma that was refractory to or progressing within 12 months after first-line treatment. Also, recently the availability of long-term outcomes from earlier trials makes it an excellent time to evaluate the Sustained response(SR) and Adverse effects associated with it. Methods: A comprehensive literature search was done of Pubmed, Embase, and Cochrane. Results: We included three trials which included two multicenter trials and one case series. Schuster et al. in their single-center case series demonstrated that Tisagenlecleucel infusion in patients with refractory diffuse large B-cell lymphoma on median follow-up at 28.6 months showed Complete remission(CR): 43%; 95% CI(18-71) Sustained remission(SR): 86%; 95% CI(13 to 98), Severe cytokine-release syndrome(CRS): 18%. On further median follow-up at 60.7 months showed a CR: 46%, overall response rate(ORR): 58%, Progression-free survival(PFS): 31% (95% CI:14-51). Good recovery in humoral and cellular response. The limitation of the trial was a relatively small number of enrolled patients. JULIET trial, a more extensive multicenter phase 2 trial involving 93 patients, demonstrated that Tisagenlecleucel infusion in patients with refractory diffuse large B-cell lymphoma on 14 months median follow-up showed an ORR: 52% (95% CI, 41 to 62), CR: 40%, Partial response(PR): 12%. On further median follow-up at 40.3 months showed CR: 39%, ORR: 53·0% (95% CI 43·5–62·4). Grade 3-4 CRS: 23%. BELINDA Trial also an extensive multicenter phase 3 trial involving 322 patients which involved patients with aggressive B cell lymphoma that was refractory to or progressing within 12 months after first-line therapy showed infusion of Tisagenlecleucel with optional bridging treatment or salvage chemotherapy and autologous HSCT Showed similar Medial event-free survival(MEFS) at three months for both groups. Progression at six weeks was 25.9% in Tisagenlecleucel vs. 13.8% in the control group. Conclusions: Tisagenlecleucel infusion is shown to have a high rate of durable response in relapsed or refractory diffuse large B-cell lymphoma in adults. Long-term follow-up showing satisfactory ORR with good recovery in cellular and humoral function. However, infusion of Tisagenlecleucel with optional bridging therapy or salvage chemotherapy and autologous HSCT inpatient with aggressive B cell lymphoma that was refractory to or progressing within 12 months after first-line therapy showed Tisagenlecleucel is not superior to standard salvage therapy needing additional studies to evaluate the benefits when used as a second-line agent.
Factors associated with death from lymphoma in a single center study.
Authors: Ma Helen , Ricks-Oddie Joni , Streja Elani , Eapen Ann , Gupta Pankaj
Published: June 2022

e19566

Background: It is well known that age, stage, and performance status are important prognostic factors in predicting survival of patients diagnosed with lymphoid malignancies. At the VA Healthcare System, many patients have comorbidities and poor performance status. We evaluated the association of clinical outcomes with lymphoma stage, subtype and performance status in US Veterans. Methods: This retrospective study included patients diagnosed with a lymphoid malignancy including diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), and peripheral T-cell lymphoma (PTCL) from January 2008 - December 2021 at the VA Long Beach Healthcare System (n = 221). Endpoints included clinically relevant hematological and non-hematological adverse events (AE), and death from lymphoma (with death from other causes as competing events). Variables of interest included aggressive lymphomas (DLBCL and PTCL, n = 85) vs indolent lymphomas (CLL, FL, MZL and MCL, n = 149), stage (early [0-2] vs advanced [3-4]), age at diagnosis (continuous variable), and performance status (Eastern Cooperative Oncology Group [ECOG] scale: good [0-2] vs poor [3-4]). Logistic regression and Cox models with Fine and Gray competing risk were performed. Results: In patients receiving first line therapy, performance status, disease type, stage, and age at diagnosis did not predict development of clinically relevant AEs with an odds ratio [OR] of 4.1 (p = 0.12, 95% CI 0.70-24), 0.36 (p = 0.06, 95% CI 0.12-1.0), 1.5 (p = 0.39, 95% CI 0.58-4.0), and 1.0 (p = 0.12, 95% 0.99-1.1), respectively. Patients with worse performance status (ECOG 3-4) and advancing age did not have a statistically higher risk of dying from lymphoma vs other causes: performance status: HR 1.7, p = 0.26, 95% CI 0.67-4.3 and age: HR 1.02, p = 0.11, 95% CI 1.0-1.1. In a multivariate analysis, patients with more advanced stage and aggressive subtype were more likely to die from lymphoma vs other causes (hazard ratio [HR] 4.1; p < 0.001, 95% CI 2.2-7.8 and 3.1; p = < 0.0001, 95% CI 1.7-5.5), respectively. Conclusions: The fact that performance status may not predict the development of AEs with first line therapy for lymphoid malignancies is relevant to clinical decision making. However, our findings need confirmation in larger prospective studies.
Treatment of patients with hematological malignancies and left-ventricular assisted device (LVAD) managed cardiomyopathy.
Authors: Cervoni-Curet Frances Natalia , Rios Adan , Yohannan Binoy
Published: June 2022

e19581

Background: An estimated 2-3% of individuals who undergo advanced heart failure therapies, such as left ventricular assist devices (LVAD) or orthotopic heart transplantation (OHT), have an antineoplastic-related cardiomyopathy. We investigated the incidence and clinical outcomes of non-ischemic or dilated cardiomyopathies on LVAD patients who have been diagnosed with lymphomas or leukemias in our institution between years 2015 - 2022. Methods: We found four cases of patients with newly diagnosed hematological malignancy who had existing underlying LVAD-dependent cardiomyopathy in our center. One patient was excluded due to loss to follow up. The other three patients were treated in the heart failure unit while concurrently managed by LVAD specialists. One patient required administration of continuous 72hr-infusion of doxorubicin to minimize the risk of right-sided ventricular failure. The response to treatment was assessed with use of PET-CT scans, bone marrow biopsies and serological markers per standard of care guidelines. Results: The median age was 54.6 years. Two were African Americans, one Caucasian and one Hispanic (lost to follow up). All patients were males. Of these four individuals, two were diagnosed with Non-Hodgkin Lymphomas (one Peripheral T-cell lymphoma, one Diffuse Large B-cell lymphoma), one with Chronic Lymphocytic Leukemia (CLL) and one with Acute Promyelocytic Leukemia (APL). Three patients completed or have ongoing chemotherapeutic treatment. All have achieved complete remission (CR 3/3) of their diseases. Conclusions: To date, there is no significant volume of data showing the administration of chemotherapy on patients with concurrent LVAD-dependent cardiomyopathies. The Peripheral T-cell lymphoma patient received anthracycline therapy via a continuous 72-hour infusion with close LVAD monitoring at the heart failure unit. After completion of total 6 cycles in 2021, he still is in complete remission. Our CLL patient, has also completed 5 cycles of rituximab and venetoclax while also maintaining disease remission. The APL patient has completed 5 cycles of arsenic trioxide and ATRA with also a complete remission of his leukemia. LVAD-dependent cardiomyopathy patients concurrently diagnosed with malignant hematological diseases, can be considered for treatment with antineoplastic therapies. Durable remission rates can be achieved while undergoing aggressive cardiovascular care.
Weekend effect on TLS admission in patients with acute leukemia and lymphoma: Nationwide analysis of mortality, HD, demographics and health care utilization.
Authors: Obeidat Khaldun , Tariq Muhammad Junaid , Gupta Shweta
Published: June 2022

e19582

Background: Tumor lysis syndrome (TLS) is a well-known complication of hematological malignancies including leukemia and lymphoma which can occur after chemotherapy or spontaneously, early recognition of TLS can be challenging sometimes. We attempted to evaluate the Weekend effect on TLS outcomes. Methods: Healthcare Cost and Utilization Project National Inpatient Sample (HCUP-NIS) was queried to identify TLS admissions between 2016-2018 in patients with diagnosis of acute leukemia and lymphoma. We studied socio-demographic differences, all-cause mortality, acute renal failure and dialysis. Secondary outcomes included mean length of stay (LOS), mean total hospital charges (THC). Statistics were performed using the t-test, univariate and multinomial logistic regression. Results: A total 1595 TLS admissions were identified (51% in lymphoma and 49% in acute leukemia), weekend admissions were 14.4% of total admissions. There was no significant difference in the baseline characteristics between the 2 groups including mean age, sex, race, median household income national quartile for patient zip code, insurance, region of hospital and location/teaching status of the hospital. Total 195 (12%) patients died in the total study group; Mortality rate among patients with lymphoma was 16% while those with leukemia was 9%. Overall mortality rate among the Weekend group compared to weekday group was insignificantly higher (20% vs 11% with P = 0.11, aOR 1.4 CI 0.56-3.46 p = 0.53). Mortality in the Weekend group was significantly higher in patients with lymphoma (30% vs 13% P = 0.04) while in leukemia patients there was no significant weekend effect (8% vs 9% P = 0.83). Total 1170 patients developed acute renal failure (aOR 1.56 Cl 0.64-3.9 p 0.32) of which 30 required dialysis, none of them was admitted in the weekend group. Mean LOS for the whole cohort was 6.47 days and mean THC was $94,954 with no significant difference between the 2 groups. Conclusions: All-cause mortality was significantly higher in patients with TLS and lymphoma admitted on the weekend (p = 0.04) compared to weekday while no weekend effect was found in TLS admissions in leukemia. Further studies are needed to clarify if this higher mortality may be associated with delay in TLS diagnosis over weekend admissions in lymphoma patients.
Post hoc analysis of a long-term safety extension study: Responses to siltuximab in idiopathic multicentric Castleman disease patients receiving on-label dosing.
Authors: Rossi Jean-Francois , Zinzani Pier Luigi , Casper Corey , Voorhees Peter M. , Fayad Luis , Kanhai Karan , Kurzrock Razelle , Van Rhee Frits
Published: June 2022

e19586

Background: Siltuximab is the only FDA- and EMA-approved therapy for idiopathic multicentric Castleman disease. Its long-term efficacy and safety were established in a 6-year extension study featuring patients who responded to treatment or had stable disease in a phase 1 or phase 2 trial. However, dosage could be adjusted at physician discretion; of 60 patients, 33 remained on the on-label dosing of 11 mg/kg administered every 3 weeks. To assess the safety and efficacy of on-label dosing, we performed a post hoc analysis in patients who maintained this dosing. Methods: A mixed-effects model was used to analyze longitudinal measurements for tumor response, C-reactive protein (CRP), hemoglobin (Hb), erythrocyte sedimentation rate (ESR), fibrinogen, albumin, and platelet counts at multiple time points. Adverse events (AEs) were also assessed. Greenhouse–Geisser correction was used to ensure that the assumption of sphericity was met for the mixed-effects model. Tukey post hoc correction was applied to determine significant differences between specific time points. Results: Of the 33 patients on 3-week dosing, one transitioned to receiving siltuximab every 6 weeks for 25 cycles but restarted 3-weekly dosing due to suspected progressive disease (PD). Disease control was observed in 31 of the 33 patients (93.9%) at their last on-study assessment (complete response [CR] in 9 [27.3%]). Quantitative analyses were performed on the 32 patients who maintained 3-weekly dosing until their last on-study assessment. Siltuximab led to sustained mean levels of CRP, Hb, ESR, fibrinogen, albumin, and platelet counts for the duration of the study. In the 19 patients with residual IL-6 activity at screening (CRP levels > 4 mg/L) there was an overall reduction in CRP from baseline at multiple time points. This group showed a trend towards improved total Hb levels, which increased by 9.43% (adjusted p = 0.048) at cycle 31, and some demonstrated an improvement in ESR, fibrinogen, and albumin levels. All patients reported AEs, mostly grade 1 or 2, with no deaths. At point of enrolment into the extension study, the three most common AEs were hypertension (36.4%), fatigue (42.4%), and pain (51.5%). Conclusions: Our findings show that long-term on-label dosage of siltuximab sustains an improved inflammatory profile and disease control.[Table: see text]
Population-wide patterns of care in mantle cell lymphoma in Australia: An analysis of the pharmaceutical benefits scheme dataset.
Authors: Tam Constantine Si Lun , Zhao Fei-Li , Liu Tom , Gauba Raj , Chuen Li Shu , Tang Boxiong
Published: June 2022

e19587

Background: The treatment landscape in patients with mantle cell lymphoma (MCL) is changing with the introduction of Bruton’s tyrosine kinase inhibitors (BTKis) and bendamustine in Australia. We sought to analyze the practice impact of the introduction of publicly funded novel agents in MCL. The objective of this study was to describe the evolving treatment patterns of Australian patients with MCL over the last 10 years using population-wide prescription records. Methods: Patients who initiated a treatment for MCL between 01/01/2011 and 07/31/2021 were extracted from the Services Australia 10% Pharmaceuticals Benefits Scheme (PBS) dataset, which includes the dispensing records for 10% of the Australian population. This dataset captures all publicly funded treatments in Australia. The index date was defined as the commencement of any drug for MCL. First-line (1L) therapy was defined as the first treatments prescribed for MCL. A patient was defined as relapsed/refractory (R/R) if they had commenced a drug which was in a different therapeutic category, or if they re-started the same regimen after a gap of more than 180 days. Descriptive analyses were conducted to examine the use of treatment regimens for the overall 10-year population by line of therapy. Analyses by calendar year were also performed to assess the changes in the treatment patterns. Results: Overall, 241 patients with MCL were identified over the study period. The majority of patients were male (68.4%), age > 60 years (84.9%), and most being aged 70-79 years (42.1% of total). Many patients were receiving comedications at baseline, including antihypertensives (44.1%), anticoagulants (14.5%), and/or antipsychotics or antidepressants (12.5%). In the overall population (2011-2021), the majority of patients had received 1L treatment with bendamustine-rituximab (BR, 53.9%), rituximab plus other regimens (27.6%), or rituximab monotherapy (11.2%). The most commonly used regimens in R/R patients at any subsequent episode of treatment included BTKi (66.3%), rituximab monotherapy (52.8%) or rituximab plus other regimens (31.5%). A trend in adoption of novel agents was observed throughout the years following their PBS listing. Analysis by calendar year showed that from 2011 to 2020 for 1L therapy, the use of BR increased from 0% to 50% and use of rituximab-containing regimen except BR decreased from 100% to 16.7%; use of BTKi increased in R/R patients from 0% to 74.7%. Conclusions: MCL treatment patterns have significantly changed in Australia since the introduction of BTKis and bendamustine-containing regimens. The use of rituximab-containing regimens except BR in 1L MCL has decreased and use of BTKis in R/R patients has increased.