bluuebunny/crossref_metadata_2025 huggingface dataset:
A nationwide analysis of healthcare utilization and outcomes of sepsis in HIV versus non-HIV patients with Hodgkin lymphoma.
Authors: Lingamaneni Prasanth , Tariq Muhammad Junaid , Baral Binav , Shrivastava Trilok , Almani Muhammad Usman , Gupta Shweta
Published: June 2021

e19520

Background: Hodgkin lymphoma (HL) is a non-AIDS defining malignancy with a high relative risk in people with HIV compared to general population. The incidence is also higher with those with higher CD4 counts. In the US, reported mortality in HIV-HL is similar to non-HIV-HL per clinical trials, but higher in studies outside clinical trials. Sepsis is a common complication during the course of HL treatment. We attempted to explore outcomes and healthcare utilization of HIV vs Non-HIV-HL patients admitted with sepsis. Methods: We identified all adult patients with HL admitted between 2016 – 2018 from Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample (NIS) database, with a primary diagnosis of sepsis. Patients with and without HIV were identified and compared for demographic differences and primary outcomes of inpatient mortality, length of stay (LOS) and hospital charges. Secondary outcomes studied included rates of septic shock (SS), acidosis, Acute Kidney Injury (AKI), Tumor Lysis Syndrome (TLS) pancytopenia, anemia, neutropenia and protein energy malnutrition (PEM). Statistics were performed using the t-test, z-test and chi-square test. Results: We identified a total of 1140 HIV-HL and 43,120 non-HIV-HL admissions of which sepsis was a principal diagnosis in 235 (20.6%) and 5390 (12.5%) admissions respectively (p < 0.0001). Compared to non-HIV-HL, HIV-HL patients were significantly younger (47.1 vs 56.8 years, p < 0.001), more likely to be men (79% vs 57%, p < 0.001), African American (47% vs 13%) and Hispanic (23% vs 14%) (p < 0.001), more likely to be on Medicaid (34% vs 18%, p < 0.001) and from low-income zip-codes (p < 0.0001). The overall inpatient mortality was lower in HIV-HL (10.6%) vs non-HIV-HL (15.8%) (p < 0.05). However, HIV-HL was associated with increased mean LOS (12.5 vs 9.1 days, p < 0.05) and higher mean hospital charges, a $39,082 difference, for each admission of HIV-HL compared to non-HIV-HL (amounting to over $9 million over 3 years). HIV-HL also had significantly high Charlson Comorbidity index of > 10 (p < 0.05) and significantly higher rates of TLS, acidosis, AKI and PEM (all p < 0.05). All other outcomes were non-significant. Conclusions: Nationwide, HIV-HL inpatients were younger minorities from lower socio-economic status zip codes and more likely to be on Medicaid compared to non-HIV-HL cohort. HIV-HL had significantly higher rates of sepsis compared to non-HIV-HL. However, despite high rates of sepsis in HIV-HL, these patients had significantly lower mortality than non-HIV-HL group but significantly higher inpatient LOS and higher hospital charges, likely related to higher comorbidity and complication burden. Prospective studies are needed to clarify these findings and identify interventions to improve secondary outcomes and healthcare utilization in HIV-HL patients.
Real-world incidence and costs of serious infections and cardiovascular complications among patients with indolent non-Hodgkin lymphoma treated with first-line ibrutinib or bendamustine/rituximab.
Authors: Irwin Debra E. , Thompson Stephen , Ribalov Rinat , Choudhry Azhar
Published: June 2021

e19528

Background: Patients with Indolent non-Hodgkin lymphoma (iNHL) have shown positive outcomes with ibrutinib monotherapy (IM) as well as bendamustine/rituximab combination (BR) therapy, but no studies have reported on patient outcomes using real-world data. The current analysis evaluated serious infections and cardiovascular complications in iNHL patients treated with first-line IM or BR therapy using US real-world data. Methods: Administrative claims from the MarketScan® Research Databases were used to identify adult patients enrolled in commercial or Medicare supplemental insurance plans based on a first prescription fill of IM or BR therapy (the index date) from 2/1/14 to 9/1/19. Patients included in the study were diagnosed with iNHL, were treatment naïve, and were continuously enrolled for ≥12 months both prior to and following the index date. Serious infections and cardiovascular complications requiring hospitalization (diagnosis code in any position) and associated inpatient costs were evaluated during a fixed 12-month follow-up period. Statistical differences in outcome distributions and costs (reported per patient per month [PPPM]) between the groups were tested. Results: Of 1,948 iNHL patients, 147 had IM and 1,058 had BR as index therapy with ≥12 months of follow-up data. Patients receiving IM were older, more often male, and more likely to have had a lower respiratory tract infection (LRTI) or atrial fibrillation (AF) during baseline compared to BR patients, otherwise the groups had similar baseline characteristics. Hospitalization for serious infections was similar for IM and BR patients during the follow-up period (17.0% vs. 14.4%; p = 0.397); among hospitalized patients, the IM and BR groups incurred similar PPPM inpatient costs ($2,839 vs. $3,954; p = 0.188). Specifically, 7.5% of IM patients had a bacterial infection hospitalization and incurred $2,561 PPPM vs 7.6% of BR patients who incurred $3,975 PPPM (both p > 0.05); 8.8% of IM patients had a LRTI hospitalization and incurred $3,629 PPPM vs 6.1% of BR patients who incurred $4,980 PPPM (both p > 0.05). Hospitalization for cardiovascular complications was similar during follow-up for IM and BR patients (15.6% vs. 12.2%; p = 0.237); among hospitalized patients, the IM and BR groups incurred similar PPPM costs ($3,777 vs. $3,862; p = 0.948). Specifically, 7.5% of IM patients had a hospitalization for AF and incurred $4,481 PPPM vs 3.6% of BR patients who incurred $4,860 PPPM (p = 0.025 and p = 0.875, respectively). Conclusions: In a real-world setting, serious infections and cardiovascular complications requiring hospitalization, including associated costs, were similar among iNHL patients treated with first-line IM or BR over 12 months, although IM patients were more likely to have an AF-related complication.
Real-world treatment patterns and outcomes in patients with follicular lymphoma in the United States.
Authors: Ta Jamie T. , Itani Taha , Shapouri Sheila , Arndorfer Stella , Julian Cristina , d’Ario Giovanni , Sud Cheryl
Published: June 2021

e19534

Background: Despite the availability of new therapies for follicular lymphoma (FL), there are limited data on the real-world treatment (tx) of FL in a contemporary cohort of patients (pts). We examined tx patterns and outcomes in pts who received FL therapy in the US. Methods: This retrospective cohort study used the nationwide Flatiron Health electronic health record-derived de-identified database. During the study, the de-identified data originated from ̃280 cancer clinics (̃800 sites of care) in the US. We selected pts aged ≥18 years, with an initial FL diagnosis (ICD-9-CM: 202.0x; ICD-10-CM: C82.0x) between January 2011 and July 2020, who had received ≥1 line of therapy (LOT) for FL (follow-up ended September 2020). The initiation date of a LOT was considered the index date for analyses by LOT. Pts with evidence of clinical trial participation during the study period, high-grade (3b) FL at diagnosis, transformed aggressive lymphoma at any time before first-line (1L) FL tx, or chemotherapy/immunotherapy or stem cell transplant 12 months before 1L FL tx, were excluded. Pt characteristics at diagnosis were assessed using descriptive statistics. Tx patterns and clinical outcomes (time to next tx [TTNT] and overall survival [OS]) were reported by LOT. Median TTNT and OS were estimated using Kaplan–Meier methods. Results: Overall, 2383 pts met all eligibility criteria. Median age at FL diagnosis was 66 years; 49.2% were male, 77.5% had low-grade (1–2) FL, and 75.2% had advanced stage (III/IV) FL at diagnosis. Median follow-up was 43.1 months, and median time from diagnosis to 1L FL tx was 38 days. Most pts received up to 2 LOTs (n=2258 [94.8%]). The most common regimens across all LOTs were rituximab-bendamustine (R-benda; n=1256 [52.7%]), R monotherapy (n=812 [34.1%]), R-CHOP (n=483 [20.3%]), R-CVP (n=172 [7.2%]), and obinutuzumab (G)-benda (n=77 [3.2%]). The use of newer FL therapies was limited across all LOTs, but more common in the third-line onwards (3L+): chemotherapy-free combinations (R-/G-lenalidomide): 2.3% (all LOTs) and 19.2% (3L+); and phosphoinositide 3-kinase inhibitors: 1.6% (all LOTs) and 21.6% (3L+). In total, 111 (4.7%) pts received G-based regimens. Median TTNT after 1L and second-line onwards (2L+) was 79.4 months and 38.3 months, respectively. Median OS was not reached (NR) and 82.9 months after 1L and 2L+, respectively (Table). Conclusions: We provide a comprehensive update on real-world tx patterns and clinical outcomes in pts with FL in the US. Chemoimmunotherapy remains the standard of care across all LOTs, though the shorter durations of TTNT and OS in 2L+ may support the role of novel therapies in this setting. Tx outcomes by LOT.[Table: see text]
Evaluation of same day pegfilgrastim (PFG) or PFG-cbqv prophylaxis of chemotherapy induced (Febrile) neutropenia (CIN/FN) in bendamustine plus rituximab (BR) and CHOP+/-R regimens in patients with lymphoma and chronic lymphocytic leukemia (CLL): Real-world, single-center experience.
Authors: McBride Ali , AlRawashdh Neda , Bartels Trace , Moore Logan , Persky Daniel O , Abraham Ivo
Published: June 2021

e19541

Background: BR and CHOP+/-R regimens are considered an intermediate FN risk (10-20%) per guidelines. Patients (pts) receiving these regimens need to be assessed for FN prophylaxis using specific risk factors. Current guidelines suggest waiting 24 hours post chemotherapy (CTX) to administer PFG due to an increased FN risk. Studies have shown equivocal outcomes between same day (D1) and next day (D2) administration. We evaluated real-world outcomes associated with D1 and D2 PFG administration in pts with lymphoma and CLL treated with these two regimens. Methods: Retrospective chart review of lymphoma or CLL pts treated with CHOP+/-R or BR and PFG or a biosimilar from 11/2013 through 11/2020 at the University of Arizona Cancer Center was conducted. Two pt cohorts were analyzed based on D1 vs D2 PFG administration timing. Outcomes of interest were the incidence of FN across all CTX cycles and after cycle 1, CIN grade 3/4, hospitalizations, antibiotics administration, and CTX dose reduction or delay. A secondary analysis compared the incidence of FN in pts receiving CHOP+/-R in our study with published studies (Burris et al, 2010 and Cheng et al, 2014) of D1 PFG in lymphoma pts. Results: Of the 116 pts meeting inclusion criteria, 103 received PFG on D1 and 13 on D2 of CTX. As shown in the Table, the incidence of 1st cycle FN was 6% vs 8% (P>0.05), FN across all cycles was 4% vs 5% (P>0.05), CIN grade 3/4, hospitalization, anti-biotic administration and dose delays/reductions incidences were 11% vs 16% (P>0.05), 8% vs 11% (P>0.05), 6% vs 32% (P=0.001), 11% vs 5% (P>0.05) for D1 vs D2, respectively. The incidence of 1st cycle FN in D1 cohort was 6% vs 19% (P=0.15) and 11% (P=0.67) in our study vs Burris et al and Cheng et al, respectively. While the incidence of FN across all cycles in D1 group was 5% vs 9% (P=0.03) and 17% (P=0.001) in our study vs Burris et al and Cheng et al, respectively. Conclusions: This data provides evidence that D1 PFG/PFG-cbqv does not increase FN or delayed engraftment risk as compared to previously published studies in lymphoma and may be safe to use after CTX has been administered.[Table: see text]
Clinical outcomes in patients relapsed/refractory after ≥ 2 prior lines of therapy for follicular lymphoma: A systematic literature review and meta-analysis.
Authors: Kanters Steve , Kahl Brad S. , Wiesinger Adriana , Gurung Binu , Limbrick-Oldfield Eve , Sudhindra Akshay , Snider Julia , Patel Anik R.
Published: June 2021

e19548

Background: Patients with follicular lymphoma (FL) can have high response rates to early lines of treatment. However, among FL patients relapsed/refractory (r/r) after ≥2 prior lines of therapies (LOT), remission tends to be shorter and there is limited treatment guidance. This study sought to evaluate the clinical outcomes for r/r FL after ≥2 prior LOT using currently available treatment options. Methods: Electronic databases were searched on June 2, 2020. Eligible studies were comparative or non-comparative interventional or observational studies of systemic therapies among adults with FL r/r after ≥2 prior LOT. Prior LOT must have included anti-CD20 monoclonal antibodies and alkylating agents, in combination or separately. Overall response rate (ORR) and complete response (CR) were analyzed using inverse-variance weighting with Freeman-Tukey double-arcsine transformations. Kaplan-Meier (KM) analysis for progression-free survival (PFS) and overall survival (OS) were conducted using digitized curves and the Guyot algorithm. Survival analyses were stratified by ≥2 prior LOT and ≥3 prior LOT groups and were restricted to the observational cohorts as a sensitivity analysis. Results: The meta-analysis included 12 studies published from 2014-2020. Sample size for response outcomes was 340, for survival outcomes with ≥2 prior LOT was 1024 and for ≥3 prior LOT was 502. The estimated ORR in the ≥2 prior LOT group was 56.0% (95% confidence interval [CI]: 47.2 – 64.5) and proportion of patients with CR was 12.2% (95% CI: 8.0 – 17.3). The median OS was 54.4 months (95% CI: 45.8 – 76.0) and median PFS was 10.3 months (95% CI: 9.3 – 11.1). The 24-month OS decreased from 66% in the ≥2 prior LOT group to 60% in the ≥3 prior LOT group (Table 1), with a similar trend in PFS at 24-month (28% vs 24%). Conclusions: This study found that few r/r FL patients with ≥2 prior LOT achieve CR, and despite some benefit, approximately 1/3 of patients die within 24 months. The shorter median PFS with increasing prior LOT suggest treatment durability is suboptimal in later LOT. These findings indicate that patients are underserved by current treatments, demonstrating a need for new treatments that can achieve high rates of response that are durable in this disease.[Table: see text]
Healthcare resource use (HRU) by infusion setting of chimeric antigen receptor T-cell (CAR-T) in patients with relapsed and refractory (r/r) diffuse large B-cell lymphoma (DLBCL): A retrospective cohort study using CMS 100% Medicare database.
Authors: Zhao Jing , Bollu Vamsi , Yang Hongbo , Dalal Anand , Tesfaye Mimi , Ma Qiufei , Lax Angela , Lim Stephen
Published: June 2021

e19550

Background: Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CAR-T therapies that were approved for r/r DLBCL in 2017 and 2018, respectively. While majority of the CAR-T infusions occur at inpatient (IP) setting in clinical trials, CAR-T infusions can also occur in the outpatient (OP) setting. This study aimed to compare the real-world HRU between IP vs. OP infusion of CAR-T among patients with r/r DLBCL. Methods: Adult patients with r/r DLBCL receiving tisa-cel or axi-cel were selected from the CMS 100% Medicare data from 2017 to 2019 and classified into IP and OP cohorts based on CAR-T infusion setting. Number of IP, OP, intensive care unit (ICU) visits, IP days, and ICU days by month post-CAR-T infusion were compared between cohorts using generalized linear models, adjusting for age, sex, race, and National Cancer Institute comorbidity index. Average length of stay (LOS) per IP episode during the first month was also described. Results: A total of 430 patients receiving CAR-T (380 IP and 50 OP) were identified. Among those with CAR-T regimen identifiable in the OP cohort, 90.2% received tisa-cel and 9.8% received axi-cel. Mean age at CAR-T infusion in IP and OP cohorts was 70.8 and 68.4 years, respectively. Most of the CAR-T infusions occurred in 2019 (66.6% in IP cohort and 74.0% in OP cohort). During the first month post-CAR-T infusion, OP cohort had significantly lower number of IP visits, IP days, ICU stays, and ICU days compared to the IP cohort. Average LOS per IP episode was 14.2 days in the IP cohort and 7.1 days in the OP cohort. Number of IP visits, IP days, and ICU days were nominally lower while number of OP visits were nominally higher in the OP cohort compared to the IP cohort in subsequent months (Table). Conclusions: Over 90% of the patients treated with CAR-T in the OP setting received tisa-cel. Patients receiving CAR-T in the OP setting had lower resource use of IP and ICU compared to patients receiving CAR-T in the IP setting.[Table: see text]
Health care utilization and outcomes of sepsis in HIV versus non-HIV patients with Burkitt Lymphoma: A nationwide analysis.
Authors: Baral Binav , Tariq Muhammad Junaid , Lingamaneni Prasanth , Baranwal Anmol , Shrivastava Trilok , Almani Muhammad Usman , Gupta Shweta
Published: June 2021

e19561

Background: Burkitt lymphoma (BL) is an aggressive AIDS-defining malignancy, the incidence of which has not declined over the last 2 decades despite use of antiretroviral therapy. HIV-BL is more advanced at diagnosis compared to non-HIV-BL with increased risks of immunosuppressive chemotherapy (Lancet Hematology 2020;7(8):e594-e600). We attempted to explore and quantify the prevalence, outcomes and healthcare utilization of HIV-BL vs non-HIV-BL patients admitted with sepsis. Methods: Healthcare Cost and Utilization Project (HCUP) National Inpatient Sample (NIS) database was queried to identify all adult HIV and non-HIV admissions with BL between 2016–2018 with a primary diagnosis of sepsis. The groups were compared for demographic differences, inpatient mortality, length of stay (LOS) and hospital charges. Secondary outcomes studied included rates of septic shock (SS), acidosis, acute kidney injury (AKI), tumor lysis syndrome (TLS), pancytopenia, anemia, neutropenia, protein energy malnutrition (PEM) and history of bone-marrow/stem-cell transplant. Statistics were performed using the t-test, z-test and chi-square test. Results: A total of 2310 HIV-BL admissions comprising 205 (8.9%) with sepsis and 11,950 non-HIV-BL admissions with 865 (7.2%) with sepsis (p = 0.006) were identified. Compared to non-HIV cohort, HIV-BL patients were significantly younger (mean age 43.6 versus 55.3 years, p = 0.001) with few over 65 years old (2.4% vs 36%, p = 0.001). Both groups had similar gender ratio, but a higher number of HIV-BL admissions were African American (AA) (51.4% vs 4.9%, p = 0.001), on Medicaid (31.7% vs 15.6%, p < 0.0001), from lowest quartile income zip codes (p < 0.0001) and more likely to be treated at teaching hospitals (73.2% vs 54.9%, p < 0.0001). The overall inpatient mortality was 21.9% in HIV-BL vs 15.6% in non-HIV-BL (p = 0.02). HIV-BL reported increased mean LOS (9 vs 8 days, p = NS) and average $39,599 more in hospital charges for each HIV-BL admission compared to non-HIV-BL with sepsis (amounting to over $8 million over 3 years). The rates of anemia, neutropenia, TLS, AKI, SS, TLS and PEM were similar (p = NS) between the groups. Conclusions: Nationwide, HIV-BL patients had significantly higher rates of sepsis despite being significantly younger. They were also more likely to be AA from lower socioeconomic zip codes and more likely to be on Medicaid. The mean inpatient LOS and hospital charges, although not statistically significant, were higher in HIV-BL compared to their non-HIV counterparts. Also, the difference in total charges for all HIV-BL admissions amounted to over $8 million extra compared to non-HIV-BL in 3 years. These trends need to be evaluated in prospective studies to help identify interventions to improve clinical outcomes and healthcare utilization.
Clinical utility of interim CT scans in patients receiving bendamustine and rituximab for first line treatment of follicular lymphoma.
Authors: Manji Farheen , Bhella Sita , Prica Anca A. , Kridel Robert , Kukreti Vishal , Kuruvilla John , Crump Michael
Published: June 2021

e19565

Background: Interim imaging with computed tomography scanning (CT) has been performed during most clinical trials of chemoimmunotherapy in patients with follicular lymphoma (FL) receiving first line systemic therapy. Based on this, interim imaging is commonly performed, but there is little evidence of its utility in clinical practice. Methods: The objective of this study was to retrospectively review outcomes of interim CTs (iCT) in adult patients with biopsy proven FL (grade 1-3a, 3b excluded) who received first line therapy with bendamustine and rituximab (BR) at Princess Margaret Cancer Centre from January 1 2013- December 31 2018. Baseline patient characteristics at diagnosis and treatment were retrieved from a prospectively populated database, and results of interim, end of treatment and end of maintenance therapy (if applicable) imaging were assessed. Disease response was assessed using Lugano response criteria as partial response (PR), complete response (CR), stable disease (SD) or progressive disease (PD). Descriptive statistics and Kaplan Meier Survival functions with a log rank test were used to analyze the data. The study was approved by the Princess Margaret Research Ethics Board. Results: A total of 108 patients were identified: mean age at diagnosis 61 years (IQR 52.4-69.5), 83% with stage III/IV disease, 27.8% bulky ( > 10cm) and median FLIPI score 2. Median follow up was 55.9 months (6.6-100.1 months). Of them, 101 patients (93.5%) had interim imaging done between cycle 2 and cycle 5 , most commonly CT scan (n = 98, 97.0%). The majority of iCTs showed a PR (n = 81, 80.1%), with a minority showing a CR (n = 11, 10.9%) and SD (n = 2, 1.9%). Seven patients had PD noted on iCT. Four patients had a second malignancy identified on biopsy of lesions found on iCT (thymoma, poorly differentiated carcinoma, lung adenocarcinoma and spindle cell tumour), 2 of whom were symptomatic at the time of iCT. Three patients had biopsy proven transformation to diffuse large B cell lymphoma (DLBCL); 2 were symptomatic at the time of iCT and only 1 had asymptomatic PD. The 3 year progression free survival (PFS) for all patients was 87.55%. Patients with a PR on iCT had similar 3 year PFS compared to those with CR (87.25% vs 90.00%, p = .52) as well as overall survival (94.80% vs 88.89%, p = .88). Conclusions: In this cohort, iCT was not useful for identifying patients with asymptomatic early progression of FL during treatment with BR. The majority of patients receiving systemic treatment for FL have at least a PR to BR on iCT, which is not associated with inferior PFS or OS compared to those with CR. Patients with symptomatic or asymptomatic PD during treatment warrant biopsy to identify histologic transformation or other malignancies. The rate of second cancers identified on iCT will be further explored in a cohort of FL patients treated with R-CVP and R-CHOP.
Prevalence and outcomes of sepsis in HIV versus non-HIV patients with diffuse large B-cell lymphoma: A nationwide analysis.
Authors: Tariq Muhammad Junaid , Baral Binav , Lingamaneni Prasanth , Gannamani Vedavyas , Almani Muhammad Usman , Gupta Shweta , Rubinstein Paul G.
Published: June 2021

e19567

Background: With the advent combined anti-retroviral therapy (ART), the survival of people living with HIV has improved, thereby increasing their prevalence, while concurrently decreasing the incidence AIDS defining malignancies. Despite its decrease, AIDS-related Diffuse Large B-Cell Lymphoma (DLBCL) remains the 3rd most common malignancy in the HIV population and an important cause of cancer related morbidity and a leading cause cancer attributed mortality. Currently the treatment modalities between HIV and non-HIV DLBCL are similar, however a comparison of the infectious complications has never been assessed. We aim to explore the prevalence and outcomes of sepsis in persons living with HIV and DLBCL versus the non-HIV DLBCL patient population. Methods: We identified all adult DLBCL patients admitted between 2016–2018 from The Nationwide Inpatient Sample (NIS) with a primary diagnosis of sepsis. Patients with and without HIV were identified and compared for demographic differences and primary outcomes of inpatient mortality, length of stay (LOS) and hospital charges. Secondary outcomes studied included rates of septic shock, acidosis, Acute Kidney Injury (AKI), Tumor Lysis Syndrome (TLS) pancytopenia, anemia, neutropenia, protein energy malnutrition (PEM) and history of bone-marrow/stem-cell transplant. Statistics were performed using t-Test, chi-square test and multivariable logistic regression. Results: There was a total of 5740 HIV-DLBCL and 158,445 non-HIV-DLBCL inpatient admissions of which 480 (8.4%) and 16085 (10.1%) respectively had sepsis (p < 0.0001). Compared to non-HIV cohort, HIV-DLBCL patients were significantly younger (47.5 versus 67 years, p < 0.001), more likely to be male (66.7% vs 55.3%, p = 0.02), Black (43% vs 7.7%) or Hispanic (18% vs 11%) (p < 0.001), more likely to be on Medicaid (44.9% vs 8.2%, p < 0.001) and lived-in low-income zip-codes (p < 0.0001). Overall adjusted inpatient mortality was not significantly different between HIV and non-HIV groups (14.6% vs 16.9%, p = NS). But HIV-DLBCL patients had significantly high Chalrson co-morbidity index (p < .0001), longer inpatient LOS (8.75 vs 8.65 days, p < 0.0001) and higher total hospital charges (average $5338 higher for each admission, p < 0.0001). HIV-DLBCL cohort also reported significantly higher TLS (7.3% vs 2.6%, p = 0.005) and PEM (42.7% vs 28.9%, p = 0.004). Other secondary outcomes were not significantly different between the groups. Conclusions: Demographic differences between the two cohorts are reflective of known racial & socio-economic disparities associated with HIV. Lower rates of sepsis in HIV cohort were not translated into improved inpatient mortality. Longer LOS and hospitalization charges in HIV patients likely due to high comorbidity burden.
Real-world evidence (RWE) study of CAR-T agents in leukemia and lymphoma patients.
Authors: Lal Lincy S. , Blauer-Peterson Cori , DaCosta Byfield Stacey , Malin Jennifer
Published: June 2021

e19573

Background: Chimeric antigen receptor T (CAR T) cell products are considered gene treatments, producing long term results, with just one infusion. Real world evidence on the two available CAR T cell products, tisagenlecleucel (T) and axicabtagene ciloleucel (AC) are limited in leukemia and lymphoma patients, specifically at the individual product level. This study presents treatment outcomes and resource utilization of these products from a payer perspective. Methods: Patients with evidence of CAR T administration per claims algorithm and from documentation from a prior authorization program from January 1, 2017 to May 30, 2020 were included; the CAR T administration was the index event. Baseline demographics and clinical characteristics, healthcare resource utilization (HCRU) for the CART T administration and pre and post CAR T administration for a fixed 6-month period, and previous treatments were captured and presented by product, using descriptive analytics. Results: The study population included 148 patients, mean age (SD): 57.4 (16.9), with 34% female, and 64% Commercial patients versus 36% Medicare patients, with a mean follow-up of 319 days (SD: 210). There were 15 leukemia patients, 119 lymphoma patients, and 14 patients with other indication in the study population; 71(48%) had evidence of being on a clinical trial during the study. The mean Charleson Comorbidity score at baseline was 3.9. Major comorbidities included anemia (71%), diseases of the heart (72%). 29(20%) patients were treated with T of which 24% were for leukemia and 76% for lymphoma and 67 (46%) were treated with AC of which 100% were for lymphoma, and 52 (35%) patients did not differentiate between products. Majority of the CAR T administration took place inpatient (84%). Baseline 6-month HCRU was 52% ER visits and 59% hospitalizations, compared to post 6-month utilization at 45% ER visits and 49% hospitalizations for the total population. 118 (80%) patients had evidence of prior treatment indicating that the CAR T was at least in the second line setting or higher. The most common priming chemotherapy was cyclophosphamide-fludarabine in 69 (47%) patients. Of the total population, 72% did not have any evidence of further treatment in the available follow-up time, specifically, 47% in the leukemia and 76% in the lymphoma populations, respectively. Conclusions: Majority of patients have evidence of prior treatments before the CAR T index date, indicating relapse. There is evidence of decrease in the HCRU subsequent to treatment, compared to pre period and 72% do not have subsequent treatment in the available follow-up time, indicating a high level of efficacy.
Safety of subcutaneous daratumumab in the treatment of plasma-cell disorders: A single-center experience.
Authors: Kye Jung , Seyer Magdalena , Patel Samit , Kim Eun-Jeong , Hewitt Rhonda , Liedtke Michaela , Iberri David Joseph
Published: June 2021

e20007

Background: Daratumumab (Dara) is a CD38-directed monoclonal antibody approved for the treatment of patients with multiple myeloma (MM) and light-chain amyloidosis (AL). Infusion-related reactions (IRRs) have been reported in 28-56% of individuals receiving the conventional intravenous (IV) formulation, necessitating slow infusions and frequent use of rescue medications to mitigate complications. Recently subcutaneous (SC) Dara received approval in MM, and randomized data suggests a lower rate of IRRs compared to IV Dara. Guidelines regarding post-injection monitoring with SC Dara are not well established. This retrospective study aims to evaluate the safety of SC Dara in patients with MM and AL, and to suggest guidelines for monitoring following SC Dara administration. Methods: This single-center retrospective study included patients treated with MM or AL receiving SC Dara between June 2020 and December 2020. The primary outcome of the study was incidence of IRRs. Secondary outcomes include timing and severity of IRRs based on CTCAE version 4.0. Results: A total of 82 patients received SC Dara during the study period. Of these 82, forty-nine (60%) had previously received Dara (Dara-exposed), and 33 patients (40%) were Dara-naïve. Eight of the 82 patients (9.8%) experienced an IRR. All were grade 1 (n=5, 63%) or grade 2 (n=3, 38%) in severity. Seven patients in the Dara-naïve group experienced an IRR (21%), and one patient in the Dara-exposed group (2%) experienced injection-site erythema with the second SC dose after transitioning from IV. Three patients experienced reactions immediately after SC Dara administration, and four patients experienced delayed reactions >4 hours after SC Dara administration (median 11.9 hours; range 5-24). Among those with delayed reactions, three experienced reactions after being discharged from the treatment area but symptoms resolved without any intervention. Conclusions: In this single-center study of patients receiving SC Dara, IRRs occurred in about 10% of patients, and were more likely with a patient’s first dose of SC Dara. All reactions were mild to moderate in severity and could be managed in the outpatient setting. We suggest that Dara-naïve patients receiving their 1st SC Dara dose be monitored for one hour after SC Dara administration. Monitoring does not appear necessary for patients transitioning from IV to SC Dara or receiving subsequent doses of SC Dara. [Table: see text]
Recent updates on bispecific T-cell engager (BiTE) antibodies in relapsed and refractory multiple myeloma.
Authors: Rafae Abdul , Wahab Ahsan , Ehsan Hamid , Christy Joshua , Saleem Tabinda , Kandah Emad , Ali Rabia , Malik Mustafa Nadeem , Ali Sundas , Saeed Sara , Anwer Faiz
Published: June 2021

e20034

Background: Bispecific T-cell engager (BiTE) antibodies are currently being studied for various hematological malignancies including relapsed and refractory multiple myeloma (RRMM). BiTE antibodies that target CD3 on T cells and antigens GPRC5D, BCMA or FcRH5 on myeloma cells are being studied in RRMM patients (pts). Methods: A comprehensive literature search was done on Pubmed, Embase, and Cochrane. The data presented in various conferences (ASH, ASCO) were also included. Results: Six clinical trials are currently evaluating anti-BCMA, anti CD3 BiTE in RRMM. Madduri et al. reported ORR of 39% in 49 pts treated with REGN5458 an anti BCMA and CD3 BiTE antibody. Grafall et. al reported an ORR of 73% with Teclistamab at 1500µg/kg SC. Harrison et al. reported ORR of 83% in 9 pts treated with 9mg of AMG 701. Lesokhin et al. reported an ORR of 33% among 18 RRMM pts at all dose levels and ORR of 75%. at dose level of 215μg/kg weekly (n=4), and 360 μg/kg weekly (n=4). Rodriguez et al. reported an ORR of 80% among 15 RRMM pts treated with TNB-383B at the dose of 40-60mg IV every 3 weeks. Topp et al reported an ORR of 70% among 10 pts treated with AMG420/BI-836909 at MTD of 400µg/d. Chari et al reported results of Talquetamab which targets GPRC5D which showed an ORR of 66% in 55 evaluable pts. ORR at RP2D (405 µg/kg SC) was 69% in 19 pts treated at this dose. Cohen et al reported results on BFCR4350A, an anti FcRH5 BiTE which showed an ORR of 53% at dose ≥3.6/20mg Q3W. Cytokine release syndrome (CRS) is a serious side effect of BiTE antibodies and was reported in 39%, 64%, 65%, 61%, 45%, 38%, 54% and 76% in studies by Madduri et al, Grafall et al., Harrison et al., Lesokhin et al., Rodriguez et al., Topp et al., Chari et al., and Cohen et al., respectively. Most of the CRS cases were grade 1-2 and resolved either by themselves or required treatment with tocilizumab and steroids. Other most common side effects are reported in table. Conclusions: The most recent data on BiTE antibodies in RRMM has shown promising results with good tolerability. However, the trials are ongoing and a longer follow up is needed.[Table: see text]
Choosing optimal therapy for relapsed refractory multiple myeloma: A systematic review and network meta-analysis.
Authors: Nadeem Mahum , Gupta Samiksha , Naqvi Syed Arsalan Ahmed , Riaz Irbaz Bin , Chakraborty Rajshekhar , Aljama Mohammed A. , Husnain Muhammad
Published: June 2021

e20037

Background: Several treatment options are available for relapsed refractory multiple myeloma(RRMM). However, in the absence of direct-comparative trials, it is unclear how to choose optimal therapy in RRMM. We conducted a network meta-analysis (NMA) to assess the comparative efficacy of different treatment options in RRMM. Methods: Standard electronic databases were searched for abstract and full-text publications of phase 2/3 randomized controlled trials (RCTs) assessing treatment regimens in RRMM. Progression free survival (PFS) , overall survival (OS), complete response (CR), and very good partial response (VGPR) were analyzed. Mixed treatment comparisons were made using fixed-effect network meta-analysis (NMA) within the frequentist framework due to sparse direct evidence. Sensitivity analyses were conducted using the Bayesian approach. Publication bias was assessed by visual inspection of comparison-adjusted funnel plots. P-score plots were used to assess relative rankings of the treatments. R statistical software v 4.0.3 was used to conduct the analyses. Results: After a review of 1137 citations, A total of 37 relevant studies were included in systematic review and 30 studies were analyzed in the network meta-analysis (29 contributed for PFS; 18 for OS; 23 for CR; 25 for VGPR). Mixed treatment comparisons showed high likelihood of PFS benefit with triplet regimens; Isatuximab-Carfilzomib-Dexamethasone (Isa-Kd; P-score: 0.98), followed by Daratumumab-Carfilzomib-Dexamethasone (DKd; P-score: 0.93), Daratumumab-Bortezomib-Dexamethasone (DVd P-score: 0.92), Elotuzumab-Pomalidomide-Dexamethasone (EPd); P-score: 0.84), and Isatuximab-Pomalidomide-Dexamethasone (Isa-Pd; P-score: 0.80) when compared to monotherapy and different doublet regimens. Isa-Kd and DKd continued to show significant PFS advantage when compared to Kd doublet. High likelihood of OS benefit was observed with Carfilzomib-Lenalidomide-Dexamethasone (KRd); P-score: 0.86) followed by Kd (P-score: 0.83), and DVd (P-score: 0.82). However, trials did not consistently report data for OS and most of the mixed treatment comparisons were statistically insignificant. Similar results were observed for CR and VGPR with triplet regimens showing better likelihood for achieving CR and VGPR. Conclusions: This NMA provide most updated evidence on different treatment options in RRMM and can serve as a contemporary guidance in the absence of head-to-head trials. The weight of current evidence favors the use of triplet regimens. Isa-Kd, DKd, DVd, EPd and Isa-Pd showed no statistically significant difference in terms of PFS in RRMM.
Recent updates on three drug combination regimen for relapsed refractory multiple myeloma.
Authors: Saleem Tabinda , Rafae Abdul , Christy Joshua Jonathan , Kuriakose Kiran , Malik Mustafa Nadeem , Kandah Emad , Qurashi Hafiz , Ali Rabia , Anwer Faiz
Published: June 2021

e20039

Background: Two drug regimens comprising proteasome inhibitors, immunomodulatory agents, or a monoclonal antibody are the standard of care for multiple myeloma. However, due to the increased relapse incidence, multiple different combination therapies are under study to treat relapsed and refractory multiple myeloma (RRMM). Methods: A comprehensive data search was done across various data sets, including PubMed, Cochrane, and Embase, using MeSH terms and keywords to include all phase III clinical trials involving three-drug regimens in the last five years. Results: We report eleven clinical trials evaluating three-drug combination regimens vs. two-drug regimens for RRMM. In 2015 Stewart et al. reported ORR of 87.1% vs. 66.7% in 396 patients treated with Carflizomib (K), Lenalidomide (R), and dexamethasone (d) compared to 396 patients treated with Rd alone. Lonial et al. reported ORR of 79% vs 66% for Eltozumab + Rd (n321) vs Rd (n=325). In 2016 San-Miguel et al. treated 387 patients with bortezomib, panobinostat + d, and 381 patients with bortezomib + d, with ORR of 40.3% vs. 35.8%. Shah J et al. compared Pembrolizumab, pomalidomide + d (n=125) to pomalidomide + d (n=124) with ORR of 34% vs 40% respectively. In 2018, Elotuzumab, pomalidomide (P) + d (n=60) vs. Pd (n=57) combination studied by Dimopoulos et al. resulted in an ORR of 53% vs. 26%. In 2019 Schjesvold et al. compared isatuximab, Pd (n=154), with Pd (n=153) with an ORR of 60% and 35%, respectively. Most recently, in 2020, Kumar et al. reported ORR of 82% with venetoclax, bortezomib (V) +d (n=194) compared to ORR of 68% with Vd (n=97). Mateos et al. reported ORR of 85% with VDd (n=251), vs 63% with Vd (n=247). Bahlis et al. reported ORR of 92.9% in 268, and Suzuki et al. reported ORR of 90.2% in 52 patients treated with DRd vs. ORR of 76.4% in 283 and ORR of 72.1% in 44 patients treated with Rd alone. In another trial, Dimopoulos et al. resulted in an ORR of 53% with KDd (n=312) compared to 75% with Kd (n=154). A summary of adverse effects is listed in table. Conclusions: Three drug regimen showed better results compared to two-drug regimens with a similar safety profile. A longer follow-up of these trials is needed to confirm this.[Table: see text]
Differences in disease characteristics and outcomes in older versus younger adults with multiple myeloma.
Authors: Jacobs Michael , Langerman Spencer , Jakubowiak Andrzej J. , Chiu Brian C , Derman Benjamin Avi
Published: June 2021

e20041

Background: Older adults are underrepresented in clinical trials in multiple myeloma (MM), as are the risk prognostication schema derived from them, which limits their generalizability to this age group. Despite appropriate fitness, older adults may not be offered the same therapies as their younger counterparts. In this study, we compared disease characteristics and their associations with outcomes in older and younger adults with MM. Methods: We obtained data for newly diagnosed MM patients from the MM Research Foundation CoMMpass registry (version IA16), a prospective observational study with highly annotated clinical data, cytogenetics, and longitudinal outcomes. Chi-square or Fisher’s exact test were used for comparisons of categorical variables. Progression free survival (PFS) and overall survival (OS) curves were constructed using the Kaplan–Meier method and compared with the log-rank test. Cox proportional hazard models were computed to estimate hazard ratio (HR) and 95% confidence interval (CI) for association between pre-treatment variables and outcomes. Results: 1,143 patients were analyzed, including 853 patients (pts) under age 70 years (< SEV) and 290 pts age 70+ years (SEV+). SEV+ had a higher frequency of ISS score 3 (p < 0.001), lower estimated glomerular filtration rate (median 57.6 vs 74.7 mL/min/1.73m2, p < 0.001), and worse ECOG performance status (PS) (p = 0.01). Of the cytogenetic abnormalities analyzed [del17p, gain1q, t(4;14), t(8;14), t(14;16), t(14;20), and hyperdiploidy], SEV+ had higher frequency of gain1q (42% vs 33%, p = 0.02) and t(14;20) (3% vs 1%, p = 0.03) compared with younger adults. SEV+ received less proteasome inhibitor + immunomodulatory imide triplet induction therapy (27% vs 55%, p < 0.001) and less frontline autologous stem cell transplant (ASCT) (22% vs 59%, p < 0.001). SEV+ were less likely to achieve >complete response to induction therapy compared to < SEV (32% vs 18%, p < 0.001). SEV+ had worse PFS (HR 1.8, 1.6-2.2, p < 0.001) and OS (2.3, 1.8-2.9, p < 0.001) compared to < SEV. On multivariate analysis, increasing ISS, gain1q, high risk gene expression profiling (UAMS70), and lack of triplet induction with frontline ASCT were associated with both poorer PFS and OS in < SEV. For SEV+, multivariate analysis revealed that increasing ISS, t(14;16), and lack of triplet+ASCT were associated with inferior PFS, while age, male sex and increasing ISS were associated with inferior OS. Conclusions: Older adults have a greater prevalence of ISS 3, gain1q, and t(14;20) compared with younger adults but only ISS translates into inferior PFS or OS within this group. Increased access to triplet induction therapy and expanding access to frontline ASCT among older adults may help to improve outcomes in this growing subset of patients.
In-depth genomic characterization of programmed cell death ligand 1 (PD-L1) expression in Chinese lung adenocarcinoma patients.
Authors: Kang Li , Liu Jun , Li Jia , Wu Lin , Xiao Yajie , Du Haijian , Zhao Zhikun , Li Xiaoting , Wu Dongfang , Zhao Zhuxiang , chen bolin
Published: June 2021

e20500

Background: Immune checkpoint blockades have revolutionized anticancer treatments for lung cancers, and PD-L1 expression has been served as crucial predictive biomarkers for immunotherapies. However, PD-L1 expression has been found to be influenced by some extrinsic or intrinsic factors in vitro or to be associated with other biomarkers in vivo. Methods: An amount of tumor tissues was taken from a biopsy or surgery for PD-L1 expression assay and genomic profiling in Chinese lung adenocarcinoma patients using extend targeted sequencing panel. In-depth retrospective analyses of clinical features, gene alternations, singling pathways and immune signatures was conducted in negative group (TPS < 1%), intermediate group (1% ≤ TPS < 50%), and high group (TPS ≥ 50%). Clinical responses to selected mutation were also evaluated from public database such as TCGA and MSKCC. Results: A total of 248 Chinese patients with lung adenocarcinoma was retrospectively identified and included in this study, consisting of negative group (n = 124, 50%), intermediate group (n = 93, 38%), and high group (n = 38, 12%). High tumor mutation burden was significantly as associated with high PD-L1 expression. In addition, PD-L1 expression was highly related with gene alternations such as PRKDC, KMT2D, ERBB2 and SETD2. Moreover, signaling pathways of DDR, TP53, cell cycles and NOTCH also obviously related with PD-L1 expression. Besides, most of patients in high PD-L1 group were determined as high-grade immune subtypes (C2-C4), showing significant higher levels of IFN-gamma, CD8+ T-cells, NK cells, NK CD56 dim cells, Th1 cells, Th2 cells (P < 0.0001). Moreover, the prognostic value of SETD2 mutation was slight positive with overall survival from MSKCC cohort (HR 1.92 [95%CI 0.90-4.10], P = 0.085), and the percentage of IFN-gamma was significantly higher in SETD2 mutant group than in wild-type subgroup ( P < 0.01). Conclusions: This study illustrated in-depth genomic profiles and immune signatures of PD-L1 expression in Chinese lung adenocarcinoma patients, which might interpret more potential molecular mechanisms for anti-cancer immunotherapy in NSCLC. In addition, SETD2 may be potential biomarkers for predicting patients’ prognosis.
Longitudinal analysis of dynamic changes of T-lymphocytes during multimodal treatment of patients with inoperable stage III NSCLC.
Authors: Hofer Thomas Philipp , Käsmann Lukas , Pelikan Carolyn , Mathur Saloni , Eze Chukwuka , Taugner Julian , Tufman Amanda , Reinmuth Niels , Belka Claus , Noessner Elfriede , Manapov Farkhad
Published: June 2021

e20503

Background: Acute lymphocytopenia is associated with poor survival in solid cancers treated with multimodal therapy. A prospective analysis of peripheral blood mononuclear cells (PBMCs) during multimodal treatment in inoperable stage III NSCLC patients was performed to assess a correlation of T-lymphocytes changes with 6-months progression-free survival rates (PFS6M). Methods: Twenty patients at median age of 65.5 years (range 33-77), 85% male, 55% with adenocarcinoma and 40% with squamous cell carcinoma, were prospectively enrolled in this study. Eighteen (90%) patients received platinum-based concurrent chemo-radiotherapy (cCRT); seven (35%) patients additional concurrent and/or sequential immune check-point inhibition (four patients nivolumab and three durvalumab); patients treated with nivolumab received induction chemotherapy. Thoracic irradiation (TRT) was applied in all patients with median cumulative dose in equivalent 2Gy fractions (EQD2) of 64Gy (range: 52-65Gy). Peripheral blood was collected 5-10 days before treatment begin (A1), on the last day of TRT (RTend), and during follow-up. Samples were analyzed using polychromatic flow cytometry. Results are reported for three time-points: A1, RTend, and 6 months after TRT (C3) or the last sample available before that time-point. Results: From A1 to RTend, 16 (80%) patients experienced severe T-cell (CD3+, CD3+CD4+, CD3+CD8+) depletion, including 3 (15%) patients who received two doses of concurrent nivolumab. T-lymphocyte nadir was independent of the absolute numbers of PBMCs before treatment begin. In two patients, T-cell count remained stable, and increased in two other patients. No correlation of dynamic changes from A1 to RTend with PFS6M was observed. From RTend to C3, T-lymphocytes recovered in 11 (55%) patients; in 6 (30%) T-cell count further decreased or remained at very low levels. For total CD3 T-cells, CD3+CD4+ and CD3+CD8+ subsets, progressive disease in the first six months after TRT was associated with a decrease of median values (P = 0.03 for total CD3+ and CD3+CD4+, P = 0.08 for CD3+CD8+ T-cells). In contrast, an increase of all medians was associated with PFS6M (P = 0.007 for total CD3+, P = 0.002 for CD3+CD4+, P = 0.06 for CD3+CD8+ T-cells). Conclusions: There is a significant difference between patients with regards to T-lymphocytes recovery after the end of TRT, which is predictive for PFS6M, with poor median recovery observed in patients with early progress.