The First Retrospective Commercial Claims-Based Analysis of CAR T Treated Patients with Relapsed or Refractory Large B-Cell Lymphoma (R/R LBCL)

Introduction: Approximately 74,000 Americans are diagnosed with Non-Hodgkin Lymphoma (NHL) each year, of whom 30% are identified as having LBCL. In recent years, two autologous anti-CD19 chimeric antigen receptor T-Cell (CAR T) therapies were approved for the treatment of patients with R/R LBCL with ≥ 2 prior systemic therapies. Objectives: To describe the demographic and clinical characteristics of the CAR T patients and to compare healthcare resource utilization (HCRU) and costs pre- and post-CAR T therapy. Methods: This pre/post-index comparison evaluated in the Optum Research Database included adult (age ≥ 18 years) commercial and Medicare Advantage (MA) enrollees, with medical benefits and evidence of medical/procedure codes indicative of CAR T therapy between 01/01/2017 and 03/31/2019. Patients must have been continuously enrolled in their commercial healthcare plan for at least 3 months prior to and 6 months after the infusion (index) unless death occurred. Patients with evidence of pre-index leukemia were excluded. Baseline demographic and clinical characteristics included age, gender, insurance type, geographic region, and comorbidities. Measures of pre/post HCRU and standardized cost (scaled as per patient per month (PPPM) values to account for variable follow-up durations) included ambulatory visits, emergency department (ED) visits, and inpatient admissions (both Intensive Care Unit (ICU) and non-ICU visits). Information on the CAR T administration index visit and length of stay (LOS) for inpatient admissions were also captured. Data analysis (descriptive statistics) was conducted using Statistical Analysis System (SAS) Version 9.4. Results: 109 patients met all inclusion criteria. The patient mean age was 59.31 (SD = 12.60), 59% were male, 70% were commercially insured, 30% MA, and the mean Quan-Charlson Comorbidity score was 3.60.Thirty patients received CAR T administration through clinical trials. Seventeen percent received CAR T therapy in a Prospective Payment System (PPS) Exempt Cancer Hospital and 83% received treatment in Inpatient PPS hospitals. The CAR T therapy index event was administered inpatient for 82% of patients and twenty patients (18%) received CAR T in the outpatient setting. The median LOS during CAR T administration was 16 days which included 52% ICU admissions. During the pre-index period, all patients experienced an ambulatory visit with an average of 15.09 visits PPPM, whereas 41% had an ED encounter for an average rate of 0.39 visits PPPM, and 44% had an inpatient stay with 0.28 PPPM. The total medical and pharmacy costs were $128K PPPM. With a median follow-up of 8.4 months, patients experienced 46% fewer ambulatory visits (average 8.14 PPPM, p-value < 0.001), 49% fewer ED visits (average 0.20 PPPM, p-value < 0.037), and 18% fewer inpatient visit rates (average 0.23 PPPM, p-value = 0.415) in the post index period (excluding the index event) than pre-index period. The mean total medical and pharmacy costs were also 49% lower at $66K PPPM (p-value < 0.008). Conclusions:Post-CAR T care was associated with lower health care utilization including fewer ambulatory visits, and ED visits and lower overall total health care costs compared to pre-CAR T care. Disclosures Purdum: Kite: Current Employment, Current equity holder in publicly-traded company. Johnson:Optum: Current Employment, Current equity holder in publicly-traded company. Bonagura:Optum: Current Employment, Current equity holder in publicly-traded company. Nyamutswa:Kite: Current Employment, Current equity holder in publicly-traded company. Elliott:Optum: Current Employment. Lal:Optum: Current Employment.

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Characteristics and Treatment Patterns of Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma Who Received ≥3 Lines of Therapies

Blood ◽

10.1182/blood-2020-140136 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 4-5

Author(s):

Jipan Xie ◽

Aozhou Wu ◽

Laura Liao ◽

Xiaoyan Du ◽

Ahmed Noman ◽

...

Keyword(s):

Treatment Duration ◽

Therapy Group ◽

B Cell Lymphoma ◽

The Novel ◽

Publicly Traded ◽

Agent Based ◽

Analysis Group ◽

Car T ◽

Novel Agent

Introduction: Treatment options continued to evolve in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), with many novel treatments available in recent years. The current study aimed to describe characteristics and treatment patterns of patients with R/R DLBCL who received ≥3 lines of therapy (LOT) using recent real-world data. Methods: This study used the PharMetrics Plus administrative claims database to identify adult patients who had ≥1 inpatient claim or ≥2 outpatient claims for DLBCL (ICD-10: C83.3) between 10/01/2015 and 09/30/2019. Patients were selected if they had ≥6-months of continuous eligibility before the first DLBCL diagnosis (index diagnosis). To capture newly diagnosed patients, the study excluded patients who had a claim for a possible DLBCL diagnosis and other hematologic malignancies (except hematologic conditions that may transform into DLBCL) before the index diagnosis and those who had stem cell transplantation (SCT) as the first treatment without prior chemotherapy (CT). An algorithm was developed to define LOT. In general, a new LOT was indicated by addition of a new drug or re-initiation of the previous LOT after a gap of ≥90 days. Pharmacologic therapies were categorized as CT or chemoimmunotherapy (CIT) or novel agent-based therapy (including brentuximab vedotin, ibrutinib, venetoclax, lenalidomide, obinutuzumab, nivolumab and pembrolizumab). SCT was counted as consolidation therapy instead of a separate line, while chimeric antigen receptor T cells (CAR-T) was counted as a separate line with preparation included (e.g., leukapheresis, bridging therapy, and lymphodepletion). Patients who received a third LOT (3L) comprised the study population, with the index date defined as the initiation date of 3L pharmacologic therapy or the infusion date of 3L SCT or CAR-T. 3L treatment distribution was described separately before and after the first CAR-T approval for DLBCL (10/18/2017). Treatment duration of 3L pharmacologic therapies was analyzed using Kaplan-Meier (KM) analysis. The proportion of patients initiating 4L during the observed follow-up period were described for all patients receiving a 3L. Due to the limited follow-up time and a high proportion of censoring, the current data was not mature to estimate rates of 4L initiation at different time points based on the KM analysis. All analyses were conducted for the overall study population and by treatment. Results: Among the 3,559 DLBCL patients receiving ≥1L treatment, 92.3% were treated with rituximab-containing regimens and 68.9% with R-CHOP or similar in 1L. There were 160 (4.5%) patients who received ≥3 LOT, with a mean age of 58.5 years and 64.4% male. Before CAR-T approval, 51 patients received 3L: 52.9% received CT/CIT, 33.3% received novel agent-based therapy, and 13.7% received SCT. After CAR-T approval, 109 patients received 3L: 45.9%, 30.3%, 7.3%, and 16.5% received CT/CIT, novel agent-based therapy, SCT and CAR-T, respectively. There were some differences in patient characteristics across treatment groups. Specifically, CAR-T patients had a relatively lower mean Charlson Comorbidity Index (CCI) score (2.9). The novel therapy group had a shorter median time from index diagnosis to index date (10.3 months). SCT patients were younger (mean 56.6 years) but with a relatively higher mean CCI score (4.2). The median follow-up time was 5.0 months and varied across treatments: from 3.9 months for CAR-T to 5.7 months for SCT. Among patients receiving pharmacologic treatments, the median treatment duration was 3.1 months and 2.8 months for the CT/CIT and novel agent-based therapy groups, respectively. During a median follow-up time of <6 months, a total of 51 (31.9%) patients initiated 4L. The proportion was 27.8% in the CAR-T group, 28.6% in the CT/CIT group, 38.0% in the novel therapy group and 33.3% in the SCT group. Conclusions: In patients with R/R DLBCL receiving 3L treatment post CAR-T approval, about 76% were treated with CT/CIT or novel agent-based therapies, though most of the novel agents are not indicated for DLBCL. CAR-T and SCT were used in 17% and 7% of patients, respectively. Treatment duration of 3L CT/CIT or novel agent-based therapies was short. A relatively high proportion of patients moved to the next LOT during a short follow-up period. These findings highlight the unmet need for more effective treatments among R/R DLBCL patients in 3L and later lines. Disclosures Xie: Analysis Group, Inc.: Other: Employee of Analysis Group, Inc., which has received consultancy fees from ADC Therapeutics, Inc.. Wu:Analysis Group, Inc.: Other: Employee of Analysis Group, Inc., which has received consultancy fees from ADC Therapeutics, Inc.. Liao:ADCT: Current Employment, Current equity holder in publicly-traded company. Du:Analysis Group, Inc.: Other: Employee of Analysis Group, Inc., which has received consultancy fees from ADC Therapeutics, Inc.. Noman:Analysis Group, Inc.: Other: Employee of Analysis Group, Inc., which has received consultancy fees from ADC Therapeutics, Inc.. Liang:Analysis Group, Inc.: Other: Employee of Analysis Group, Inc., which has received consultancy fees from ADC Therapeutics, Inc.. Camardo:ADCT: Current Employment, Current equity holder in publicly-traded company. Chen:ADCT: Current Employment, Current equity holder in publicly-traded company.

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Prevalence of Vaso-Occlusive Crises in Patients with Sickle Cell Disease: A Retrospective US Claims Database Analysis

Blood ◽

10.1182/blood-2020-140756 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 8-9

Author(s):

Abiola Oladapo ◽

Elyse Swallow ◽

Allison Briggs ◽

Miriam L. Zichlin ◽

Bjorn L Mellgard

Keyword(s):

Health Care ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Clinical Characteristics ◽

Cell Disease ◽

Publicly Traded ◽

Database Analysis ◽

Claims Database ◽

Blood Disorder ◽

The Mean

Introduction: Sickle cell disease (SCD) is an inherited blood disorder affecting ~100,000 individuals in the US. SCD is considered a chronic, lifelong condition that requires comprehensive management. Vaso-occlusive crises (VOCs) are the most common complications of SCD, resulting in intense pain and potential irreversible organ damage. The objective of this study was to characterize the demographic and clinical characteristics of patients with SCD. Methods: A retrospective database analysis was conducted using data from the IBM MarketScan Commercial Claims and Medicare-Supplemental Claims database (July 1, 2013 to June 30, 2018). Patients were included if they met the following criteria: ≥2 diagnoses of SCD on different claims between July 1, 2013 and January 1, 2017, ≥6 years of age on January 1, 2017, and continuous enrollment throughout the 1-year study period (January 1, 2017 to December 31, 2017). Descriptive statistics were used to assess patient demographics (age and sex) and clinical characteristics (Charlson Comorbidity Index [CCI] and other selected comorbidities). In addition, the following outcomes were assessed: the proportion of patients who experienced ≥1 VOC, the frequency of VOCs by care setting, the duration of inpatient VOCs, the monthly VOC risk, and the time between subsequent VOCs. Results: A total of 8174 patients met the inclusion criteria. The mean (± standard deviation [SD]) age was 40.8 (±19.5) years and 63.5% of the patients were female. The mean (±SD) CCI was 0.6 (±1.3), with chronic pulmonary disease, diabetes, renal disease, cerebrovascular disease, and stroke identified as the most common comorbidities. Approximately 20% (n=1659) of patients experienced ≥1 VOC and the mean monthly VOC risk was 0.07 (±0.19). Among patients with ≥1 VOC, the mean (±SD) number of VOCs was 5.2 (±7.7) and the median (interquartile range) time from first to second VOC was 2.4 (0.5-8.2) months. Approximately 18% (n=1461) of patients experienced ≥1 VOC managed in an outpatient setting and 10% (n=844) of patients experienced ≥1 VOC managed in an inpatient setting. Approximately 8% (n=646) of patients experienced ≥1 inpatient and ≥1 outpatient VOC during the study period. Among patients with ≥1 outpatient VOC, the mean (±SD) number of outpatient VOCs was 4.6 (±6.9); among patients with ≥1 inpatient VOC, the mean (±SD) number of inpatient VOCs was 2.2 (±2.3) and the mean (±SD) inpatient VOC duration was 6.6 (±6.4) days. Conclusions: VOCs are common complications of SCD, affecting a subset of patients who often experience recurrent VOC episodes requiring professional health care. VOCs are associated with a significant disease burden on the patient and, potentially, the health care system. Disclosures Oladapo: Takeda:Current Employment, Current equity holder in publicly-traded company.Swallow:Analysis Group, Inc.:Current Employment.Briggs:Analysis Group, Inc.:Current Employment.Zichlin:BMS:Other: Employee of Analysis Group Inc., which received consulting fees.Mellgard:Baxalta US Inc., a Takeda company:Current Employment, Current equity holder in publicly-traded company.

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Real-World Treatment Patterns, Healthcare Resource Utilization and Associated Costs Among Patients with Chronic Myeloid Leukemia in Later Lines of Therapy

Blood ◽

10.1182/blood-2020-136074 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 8-9

Author(s):

Ehab L. Atallah ◽

Rodrigo Maegawa ◽

Dominick Latremouille-Viau ◽

Carmine Rossi ◽

Annie Guerin ◽

...

Keyword(s):

Medical Costs ◽

Healthcare Resource Utilization ◽

Treatment Patterns ◽

Publicly Traded ◽

Pharmaceutical Corporation ◽

Analysis Group ◽

Ed Visits ◽

The Mean ◽

Line Of Therapy

Introduction: Despite advances in tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukemia (CML), there remains a sizeable proportion of patients (pts) with CML in chronic phase who are refractory or intolerant to these agents. A good understanding of the most recent real-world patterns of care in these pts is necessary in order to provide context for assessing the potential benefits of new treatments undergoing clinical development. The aim of this study was to evaluate treatment patterns in CML pts cycling through TKI therapies achieving later lines of therapy, and to estimate their healthcare resource utilization (HRU) and costs. Methods: Adult pts with CML in the United States who received at least 3 lines of TKI therapy were identified in the IBM MarketScan Commercial and Medicare Supplement databases (Q1/2001-Q2/2019). Treatment patterns were observed from CML diagnosis. Pt characteristics were measured during the 6 months prior to third line (3L) initiation (baseline period). All-cause HRU (inpatient [IP] admissions and days, days with outpatient [OP] services, and emergency department [ED] visits) and costs (medical and pharmacy) were measured 1) during the course of 3L therapy (from 3L initiation to termination) and 2) between 3L initiation and end of follow-up (stem cell transplant [SCT], or end of data availability/health plan coverage). HRU was reported using monthly incidence rates per 100 pts (IR/100pts); costs (2019 USD) were evaluated per-pt-per-month (PPPM) from a payer's perspective. Results: Of the 48,168 pts identified with CML, a total of 296 CML pts initiated 3L therapy; median age was 58.5 years (30% were aged ≥65 years) and 50% were female. The mean follow-up period from CML diagnosis was 57.8 months and from 3L initiation was 24.5 months. Most pts had their first CML diagnosis in or after 2010 (71%) and achieved 3L in or after 2014 (50%). At baseline, the mean modified Charlson Comorbidity Index score (excluding CML) was 1.6 with 24% of pts with a score ≥3, 64% of pts had a moderate or severe Darkow Disease Complexity Index, and the most prevalent comorbidities were hypertension (45%) and diabetes (25%); 21% of pts (i.e., ≥1 indicator of congestive heart failure, cirrhosis, or end-stage renal disease, or ≥75 years old). The most common sequences of TKIs from first line (1L) to 3L were imatinib → dasatinib → nilotinib (28%), imatinib → nilotinib → dasatinib (16%), imatinib → dasatinib → imatinib (9%), and dasatinib → imatinib → nilotinib (5%). The mean duration of 1L, second line (2L), and 3L therapy was 14.9, 10.4, and 15.6 months, respectively; 62% of pts were still in 3L at the end of follow-up. Only one patient received SCT after 3L. The most common TKIs received at each line were imatinib in 1L (65%), dasatinib in 2L (49%), and nilotinib in 3L (36%). The mean treatment-free period (time between line of therapy termination and next line initiation) between 1L and 2L was 1.3 months, 2.6 months between 2L and 3L, and 1.5 months between 3L and 4L. During 3L therapy, pts had a monthly IR/100pts of 3.4 IP admissions, 21.2 IP days, 248.8 OP days, and 10.2 ED visits (Figure 1A). Pharmacy costs accounted for 69% of the mean total costs of $15,192 PPPM, with medical costs accounting for the remainder (Figure 1B). In 3L therapy and later, pts had a monthly IR/100pts of 3.5 IP admissions, 28.7 IP days, 252.2 OP days, and 10.0 ED visits (Figure 1A). Pharmacy costs accounted for 49% of the mean total costs of $18,767 PPPM, with medical costs mainly driven by IP costs (Figure 1B). Conclusions: This study characterized CML pts receiving later lines of therapy, a clinical population which has not been previously well studied with important unmet treatment needs as they repetitively fail TKI therapy. Although the majority of pts were likely fit for SCT, SCT was rare. In addition, pts quickly switched to the subsequent line of therapy, both facts suggesting that an important proportion of pts were intolerant to previous TKIs. While pharmacy costs accounted for nearly half of the total cost burden during 3L, the proportion of medical costs PPPM took more importance following 3L therapy, with IP costs being the primary cost drivers for this increase. These findings support the need for better treatment options in pts with CML undergoing later lines of therapy. Disclosures Atallah: Novartis Pharmaceutical Corporation: Consultancy; Jazz: Consultancy; Pfizer: Consultancy; Takeda: Consultancy, Research Funding; Abbvie: Consultancy; Genentech: Consultancy. Maegawa:Novartis Pharmaceutical Corporation: Current Employment, Current equity holder in publicly-traded company. Latremouille-Viau:Novartis Pharmaceutical Corporation: Consultancy, Other: Dominique Latremouille-Viau is an employee of Analysis Group, Inc. which received consultancy fees from Novartis.; Sanofi Genzyme: Consultancy, Other: Dominique Latremouille-Viau is an employee of Analysis Group, Inc. which received consultancy fees from Sanofi Genzyme.. Rossi:Novartis Pharmaceutical Corporation: Consultancy, Other: Carmine Rossi is an employee of Analysis Group, Inc. which received consultancy fees from Novartis.. Guerin:Abbvie: Consultancy, Other; Sanofi Genzyme: Consultancy, Other: Annie Guerin is an employee of Analysis Group, Inc. which received consultancy fees from Sanofi Genzyme.; Novartis Pharmaceuticals Corporation: Consultancy, Other: Annie Guerin is an employee of Analysis Group, Inc. which received consultancy fees from Novartis.. Patwardhan:Novartis Pharmaceutical Corporation: Current Employment, Current equity holder in publicly-traded company.

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SAT0267 ROLE OF AGGRESSIVE IMMUNOSUPPRESSION ON SUBGLOTTIC STENOSIS IN GRANULOMATOSIS WITH POLYANGIITIS: RETROSPECTIVE ANALYSIS OF A MONOCENTRIC COHORT

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2582 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1076.1-1077

Author(s):

L. Moroni ◽

L. Giudice ◽

G. A. Ramirez ◽

S. Sartorelli ◽

A. Cariddi ◽

...

Keyword(s):

Medical Treatment ◽

Clinical Characteristics ◽

Granulomatosis With Polyangiitis ◽

Balloon Catheter ◽

Subglottic Stenosis ◽

Damage Accrual ◽

The Mean ◽

The One

Background:Subglottic stenosis (SGS) is defined as airway narrowing below the vocal cords and is a common and potentially life-threatening manifestation of Granulomatosis with Polyangiitis (GPA), with an estimated prevalence of 16-23% (1). Balloon catheter dilation is effective in GPA-related SGS, but relapses are frequent. Little is known about the role of immunosuppression in this setting.Objectives:to analyse the clinical characteristics of a monocentric GPA cohort, describe phenotype differences among patients with and without SGS and investigate the role of surgical and medical treatments on relapse risk and general outcome.Methods:Biopsy-proven patients with SGS were identified by review of medical charts among a cohort of patients with GPA, classified according to the algorithm of the European Medicine Agency (2). The clinical characteristics of patients with SGS were retrospectively collected over a median follow-up time of 15.9 years and compared to those of patients without SGS.Results:Fourteen patients with SGS-GPA were identified, with a female to male ratio of 1:1 and a prevalence of 29.2% among the cohort. The mean ± SD age at GPA onset was 30.8 ± 14.4 years, with a mean time from GPA diagnosis to SGS onset of 4.7 ± 4.2 years. ANCA were positive in 78.6% (54.0% anti-PR3, 18.1% anti-MPO and 27.9% IFI only). The mean Birmingham Vasculitis Activity Score (BVAS) at onset was 10.0 ± 5.6. The main clinical manifestations associated with SGS were crusty rhinitis (100%), sinusitis (78%), pulmonary disease (72.7%), otitis/mastoiditis (50%), glomerulonephritis (42.9%), orbital pseudotumor (28.6%). Six patients (42.9%) received medical treatment only, other six (42.9%) had one to three balloon dilations and two (14.2%) underwent four or more procedures. Eight patients had no SGS relapse (maximum one dilation) and they all received immunosuppression with rituximab (RTX), cyclophosphamide (CYC) or azathioprine (AZA). All patients who received no immunosuppression, methotrexate (MTX) or mycophenolate (MMF) had at least one relapse. Patients treated with MTX or MMF had a mean relapse-free survival of 13.1 months, which was comparable to the one of patients not receiving medical treatment (40.2 months; p=NS) and shorter than the one of patients receiving CYC or RTX (153.2 months; p=0.032). CYC use also inversely correlated with the number of surgical procedures (r=-0.691, p=0.006). Compared to patients without SGS (31 consecutive patients with at least 4 years of follow-up), patients with SGS-GPA had an earlier disease onset (mean age 30.8 vs 50.4 years; p<0.001), but with lower BVAS (mean 10.0 vs 15.3; p=0.013) and showed a higher prevalence of crusty rhinitis (100% vs 67.7%; p=0.019). No difference was observed in damage accrual over time between the two groups.Conclusion:Subglottic stenosis is highly prevalent in patients with GPA and may define a milder disease subset occurring more frequently in younger patients. MTX and MMF might be insufficient to prevent SGS relapses requiring balloon dilation. Aggressive immunosuppression (CYC or RTX) might have a non-redundant role in this setting and reduce the risk of relapses.References:[1]Quinn KA, et al. Subglottic stenosis and endobronchial disease in granulomatosis with polyangiitis. Rheumatology 2019; 58 (12), 2203-2211.[2]Watts R, et al. Development and validation of a consensus methodology for the classification of the ANCA associated vasculitides and polyarteritis nodosa for epidemiological studies. Ann Rheum Dis 2007; 66: 222-7.Disclosure of Interests:Luca Moroni: None declared, Laura Giudice: None declared, Giuseppe Alvise Ramirez: None declared, Silvia Sartorelli: None declared, adriana cariddi: None declared, Angelo Carretta: None declared, Enrica Bozzolo: None declared, Lorenzo Dagna Grant/research support from: The Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR) received unresctricted research/educational grants from Abbvie, Bristol-Myers Squibb, Celgene, Janssen, Merk Sharp & Dohme, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI., Consultant of: Prof Lorenzo Dagna received consultation honoraria from Abbvie, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI.

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POS0826 SKIN LIMITED IGA VASCULITIS IN ADULTS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1383 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 666.1-666

Author(s):

A. Hočevar ◽

J. Ostrovrsnik ◽

K. Perdan-Pirkmajer ◽

M. Tomsic ◽

Z. Rotar

Keyword(s):

Clinical Characteristics ◽

Systemic Disease ◽

Elevated Serum ◽

Skin Lesions ◽

Current Smoker ◽

P Value ◽

Symptom Duration ◽

Iga Vasculitis ◽

Reactive Protein

Background:IgA vasculitis (IgAV) could be limited to skin or evolve into a systemic disease, affecting characteristically joints, gastrointestinal tract and/or kidneys.Objectives:We aimed to look for differences between adult IgAV patients with disease limited to skin compared to systemic IgAV.Methods:Medical records of histologically proven adult IgAV cases, diagnosed between January 2010 and December 2020 at our secondary/tertiary rheumatology centre were analyzed.Results:During the 132-month observation period we identified 328 new IgAV cases (59.5% males, median (IQR) age 64.3 (45.1; 76.1) years). Ninety-four (40.2%) patients had skin limited disease, and the rest systemic IgAV.Clinical differences between skin limited and systemic adult IgAV are presented in table 1. Adults with IgAV limited to skin were significantly older, had less commonly skin lesions above the waistline and a lower level of C reactive protein compared to patients with a systemic disease. There were no differences in the frequency of skin necroses between the compared IgAV subgroups. The frequency of potential vasculitis triggers (prior infections, new medications, malignancy) was similar between the compared subgroups.Table 1.Clinical characteristics of IgA vasculitis patients with skin limited and systemic diseaseClinical characteristicsSkin limited IgAV (94)Systemic IgAV (234)P valueMale gender (%)54.361.50.263Age (years)*68.0 (55.0-80.5)61.5 (41.7-75.8)0.007Current smoker (%)13.821.80.123Antecedent infection (%)28.733.80.434New medication23.423.51.0History of cancer12.810.70.569Symptom duration (days)*7 (5-21)8 (5-14)0.756Purpura above waistline36.255.60.002Skin necroses (%)52.145.70.329ESR /mm/h) *32 (18-52)34 (17-53)0.873CRP (g/l) *13.5 (1-32)30 (11-68)<0.001Elevated serum IgA (%)50.649.10.892Legend: * median and IQR;Follow up data were available for 250 (76.2%) patients. During the follow up of median (IQR) 12.5 (6.8 – 22.4) months 35 patients relapsed (13/70 (18.6%) with skin limited IgAV and 22/180 (12.2%) with systemic IgAV, p= 0.224).Conclusion:Skin limited IgAV was associated with older age and less extensive skin puprura in adults. However, relapses of purpura were as common as in systemic IgAV.Disclosure of Interests:None declared

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Long-Term Follow-Up of Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy

Journal of Clinical Oncology ◽

10.1200/jco.20.01467 ◽

2020 ◽

Vol 38 (32) ◽

pp. 3805-3815

Author(s):

Kathryn M. Cappell ◽

Richard M. Sherry ◽

James C. Yang ◽

Stephanie L. Goff ◽

Danielle A. Vanasse ◽

...

Keyword(s):

T Cell ◽

Cell Therapy ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

T Cell Therapy ◽

Car T Cell ◽

Car T

PURPOSE Anti-CD19 chimeric antigen receptors (CARs) are artificial fusion proteins that cause CD19-specific T-cell activation. Durability of remissions and incidence of long-term adverse events are critical factors determining the utility of anti-CD19 CAR T-cell therapy, but long-term follow-up of patients treated with anti-CD19 CAR T cells is limited. This work provides the longest follow-up of patients in remission after anti-CD19 CAR T-cell therapy. METHODS Between 2009 and 2015, we administered 46 CAR T-cell treatments to 43 patients (ClinicalTrials.gov identifier: NCT00924326 ). Patients had relapsed B-cell malignancies of the following types: diffuse large B-cell lymphoma or primary mediastinal B-cell lymphoma (DLBCL/PMBCL; n = 28), low-grade B-cell lymphoma (n = 8), or chronic lymphocytic leukemia (CLL; n = 7). This report focuses on long-term outcomes of these patients. The CAR used was FMC63-28Z; axicabtagene ciloleucel uses the same CAR. Cyclophosphamide plus fludarabine conditioning chemotherapy was administered before CAR T cells. RESULTS The percentages of CAR T-cell treatments resulting in a > 3-year duration of response (DOR) were 51% (95% CI, 35% to 67%) for all evaluable treatments, 48% (95% CI, 28% to 69%) for DLBCL/PMBCL, 63% (95% CI, 25% to 92%) for low-grade lymphoma, and 50% (95% CI, 16% to 84%) for CLL. The median event-free survival of all 45 evaluable treatments was 55 months. Long-term adverse effects were rare, except for B-cell depletion and hypogammaglobulinemia. Median peak blood CAR-positive cell levels were higher among patients with a DOR of > 3 years (98/µL; range, 9-1,217/µL) than among patients with a DOR of < 3 years (18/µL; range, 0-308/μL, P = .0051). CONCLUSION Complete remissions of a variety of B-cell malignancies lasting ≥ 3 years occurred after 51% of evaluable anti-CD19 CAR T-cell treatments. Remissions of up to 9 years are ongoing. Late adverse events were rare.

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Cytokine release syndrome and neurological event costs in lisocabtagene maraleucel–treated patients in the TRANSCEND NHL 001 trial

Blood Advances ◽

10.1182/bloodadvances.2020003531 ◽

2021 ◽

Vol 5 (6) ◽

pp. 1695-1705

Author(s):

Jeremy S. Abramson ◽

Tanya Siddiqi ◽

Jacob Garcia ◽

Christine Dehner ◽

Yeonhee Kim ◽

...

Keyword(s):

Health Care ◽

T Cell ◽

B Cell Lymphoma ◽

Cytokine Release ◽

Cytokine Release Syndrome ◽

System Perspective ◽

Cell Therapies ◽

Car T Cell ◽

Car T ◽

Grade 3

Abstract Chimeric antigen receptor (CAR) T-cell therapies have demonstrated high response rates in patients with relapsed/refractory large B-cell lymphoma (LBCL); however, these therapies are associated with 2 CAR T cell–specific potentially severe adverse events (AEs): cytokine release syndrome (CRS) and neurological events (NEs). This study estimated the management costs associated with CRS/NEs among patients with relapsed/refractory LBCL using data from the pivotal TRANSCEND NHL 001 trial of lisocabtagene maraleucel, an investigational CD19-directed defined composition CAR T-cell product with a 4-1BB costimulation domain administered at equal target doses of CD8+ and CD4+ CAR+ T cells. This retrospective analysis of patients from TRANSCEND with prospectively identified CRS and/or NE episodes examined relevant trial-observed health care resource utilization (HCRU) associated with toxicity management based on the severity of the event from the health care system perspective. Cost estimates for this analysis were taken from publicly available databases and published literature. Of 268 treated patients as of April 2019, 127 (47.4%) experienced all-grade CRS and/or NEs, which were predominantly grade ≤2 (77.2%). Median total AE management costs ranged from $1930 (grade 1 NE) to $177 343 (concurrent grade ≥3 CRS and NE). Key drivers of cost were facility expenses, including intensive care unit and other inpatient hospitalization lengths of stay. HCRU and costs were significantly greater among patients with grade ≥3 AEs (22.8%). Therefore, CAR T-cell therapies with a low incidence of severe CRS/NEs will likely reduce HCRU and costs associated with managing patients receiving CAR T-cell therapy. This clinical trial was registered at www.clinicaltrials.gov as #NCT02631044.

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Systematic Literature Review of the Clinical Evidence in Relapsed/Refractory (R/R) Large B-Cell Lymphoma

Blood ◽

10.1182/blood-2019-127664 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5821-5821

Author(s):

David G. Maloney ◽

Fei Fei Liu ◽

Lisette Nientker ◽

Cathelijne Alleman ◽

Brian Hutton ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

T Cell Therapy ◽

Car T Cell ◽

Large B Cell Lymphoma ◽

Car T ◽

Large B Cell

Introduction: Large B-cell lymphoma (LBCL) is the most common subtype of non-Hodgkin lymphoma. Frontline treatment is curative in ~60% of patients (pts); however, ~30% of pts relapse and ~10% are refractory to frontline treatment. Treatment options for pts with relapsed/refractory (R/R) disease, especially in the third-line or greater (3L+) setting, have been primarily salvage chemotherapies (CTs). Recently, 2 CAR T cell products, axicabtagene ciloleucel (Yescarta®) and tisagenlecleucel (Kymriah®), and the antibody-drug conjugate, polatuzumab vedotin (Polivy®), were approved in the 3L setting. A systematic literature review (SLR) of R/R LBCL was conducted to identify relevant evidence on clinical outcomes in LBCL pts, including these new therapies, within the second-line and greater (2L+) or 3L+ setting, and to define the unmet medical need. Methods: This SLR was conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions and European Union Health Technology Assessment requirements. The review identified randomized and nonrandomized/observational studies within R/R LBCL, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma grade 3B (FL3B), primary mediastinal large B-cell lymphoma (PMBCL), DLBCL transformed from indolent lymphomas, and R/R DLBCL with secondary central nervous system (SCNS) involvement. Sources were EMBASE, MEDLINE, The Cochrane Library, and clinical conferences (ASCO, ESMO, EHA, ASH, ICML, AACR, and EORTC) from Jan 2000 to Apr 2019. Results : Following screening of 8683 database records and additional sources, 103 publications covering 78 unique studies were identified. Studies identified were characterized by line of treatment and R/R LBCL subtype (Figure). OS, PFS, DOR, OR, and safety observed from the identified studies were described. Disease subtypes, pt eligibility criteria, and length of follow-up varied notably across studies. In the 3L+ population, 11 salvage CT and 2 CAR T cell therapy studies reported survival outcomes. With salvage CT, the reported ORR across studies ranged from 0% to 54%, while CR ranged from 5.6%-31%. Median OS (mOS) ranged between 3-9 months, with one outlying study reporting mOS at 20 months. Median PFS (mPFS) reported within the salvage CT studies ranged from 2-6 months. Among CAR T cell therapies, pts treated with axicabtagene ciloleucel (n=101) reported a CR rate of 58% and median DOR (mDOR) was 11.1 months after a median follow-up of 27.1 months. mPFS was 5.9 months and mOS was not reached. At a median follow-up of 19.3 months, pts treated with tisagenlecleucel (n=115) had a CR of 40% but the mDOR was not reached. mOS was 11.1 months for all infused patients. In the 2L+ transplant-eligible population (36 studies), pts who received high-dose CT + HSCT achieved mOS between 9 months to 5 years. In the transplant noneligible population, 16 studies reported mOS between 3-20 months. Studies involving mixed transplant-eligible and noneligible populations (30 studies) reported mOS of 1-17 months. A few studies with limited sample sizes were found to report outcomes in LBCL subtypes (eg, PMBCL, SCNS lymphoma, DLBCL transformed from non-FL indolent lymphoma, FL3B). In the 3L+ setting, 1 study reported that mOS was not reached after a median of 6.6 months. In the 2L+ setting, 4 studies reported mPFS and mOS outcomes ranging between 2-9 months and 10-16 months, respectively. Among studies assessing safety of salvage CTs in R/R LBCL, neutropenia, leukocytopenia, thrombocytopenia, and infections were the most commonly reported adverse events (AEs), with neutropenia being the most reported. Among the 3 studies reporting safety outcomes of CAR T cell therapy, data suggest that hematologic AEs (possibly related to lymphodepleting CT), cytokine release syndrome, and neurotoxicity are the most reported. Conclusions : Despite the availability of new therapies for 2L+ and 3L + LBCL, examination of the current evidence has shown that there exists a high unmet need for additional therapeutic options that provide favorable benefit/risk and durable response for these patients. Furthermore, limited data are available for the rarer subtypes of LBCL. Both findings represent important treatment gaps for R/R LBCL that must be addressed in future research geared toward improvement of the current treatment landscape. Disclosures Maloney: Juno Therapeutics: Honoraria, Patents & Royalties: patients pending , Research Funding; Celgene,Kite Pharma: Honoraria, Research Funding; BioLine RX, Gilead,Genentech,Novartis: Honoraria; A2 Biotherapeutics: Honoraria, Other: Stock options . Liu:Celgene Corporation: Employment. Nientker:Celgene Corporation: Consultancy; Pharmerit Cöoperatief U.A.: Employment. Alleman:Pharmerit Cöoperatief U.A.: Employment; Celgene Corporation: Consultancy. Garcia:Celgene: Employment, Equity Ownership.

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Lack of Prognostic Significance of Pre-Treatment Total Metabolic Tumor Volume (TMTV) in Diffuse Large B-Cell Lymphoma (DLBCL)

Blood ◽

10.1182/blood-2018-99-113791 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1720-1720

Author(s):

Mayur Narkhede ◽

Sadaf Qureshi ◽

Maryam Yazdy ◽

Roxanna Juarez ◽

Giuseppe Esposito

Keyword(s):

Ct Scan ◽

B Cell ◽

Prognostic Significance ◽

B Cell Lymphoma ◽

Pet Ct ◽

The Mean ◽

Pre Treatment ◽

Pet Ct Scan ◽

Stage Stage

Abstract Background DLBCL is the most common non-Hodgkin lymphoma (NHL), making up about 30%-40% of NHL in the U.S. PET-CT is recommended as the most accurate imaging technique in DLBCL for staging and response assessment. Pretreatment assessment of PET-CT scan derived metrics such as TMTV has been shown to correlate with PFS and/or overall survival (OS) in DLBCL (Sasanelli 2014) We attempted to replicate this finding using EFS at 24 months as a primary endpoint and compare it with pre-treatment TMTV, TLG and cell of origin (COO). Methods 47 pts with newly diagnosed DLBCL and treated with R-CHOP at our institution between 2014 to 2018 were identified from our electronic medical record system for retrospective analysis after IRB approval. All pts had a pretreatment PET-CT scan available for TMTV measurement. All pts had a pretreatment biopsy which were reviewed along with their clinical information regarding treatment outcome and follow up. Patients were classified as to germinal center B cell (GCB) and non-GCB based on immunochemistry using the Hahn's algorithm. PET-CT scans were reviewed by two nuclear medicine physicians using synovia software, and measurements for TMTV and TLG were recorded. TMTV was calculated using a threshold of 41% of the max pixel value (based on prior studies) to draw the volume of interest (VOI) for a lesion. Pooled t-test was performed to compare TMTV, TLG and COO with EFS at 24 mos. Chi-Square test compared TMTV with COO Results Median age of pts was 58 years, with a median duration of follow up of 26 months. There were 33% with limited stage (Stage I or II) and 67% were advanced stage (Stage III or IV). The mean pretreatment TMTV and pretreatment TLG was 295cm3 and 4519 units. 49% were GCB subtype and 47 % non-GCB. Amongst all patients 19.2 % had an event within 24 mos. When TMTV was compared to EFS at 24 months the mean TMTV was 304 for those who had an event versus 294 without (p=0.95). TLG compared to EFS at 24 months showed a mean TLG of 3391 for those who had an event versus 4914 without (P=0.40). GCB and non-GCB had mean TMTV of 264 and 339 respectively with p =0.59. COO when compared to TLG had means of 4365 and 4933 for GCB and non-GBB respectively with p=0.79.Whereas there was no correlation between stage and COO (p=0.4296) TMTV correlated with Ann Arbor staging (p=0.0002). Conclusion This retrospective study failed to demonstrate a correlation between pre-treatment TMTV, TLG, COO and EFS at 24 months revealing the lack of prognostic significance of pretreatment PET scan derived metrics in DLBCL. Prior studies with TMTV did not evaluate EFS at 24 months as an endpoint and therefore, longer follow up might be needed to demonstrate prognostic significance of pretreatment TMTV minimizing it clinical significance. The different subtypes of DLBCL based on COO as assessed by Hahns algorithm also did not differ in their disease burden as measured by TMTV. Disclosures No relevant conflicts of interest to declare.

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Observations on radiological correction of acetabular dysplasia by Dega transiliac osteotomy

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20171831 ◽

2017 ◽

Vol 5 (5) ◽

pp. 1991

Author(s):

Wazir Fahad Jan ◽

Sanjay Sarup ◽

Mohd Yahya Dar ◽

Alamgir Jahan ◽

Ovais Nazir Khan

Keyword(s):

Acetabular Dysplasia ◽

Mean Value ◽

P Value ◽

Preoperative Period ◽

Radiological Parameters ◽

Male Patients ◽

The Mean ◽

Paediatric Orthopaedic ◽

Age Range

Background: Several osteotomies have been described for the correction of acetabular dysplasia associated with variable outcomes. The purpose of our study was to evaluate the effect of Dega transiliac osteotomy in radiological correction of acetabular dysplasia by assessing the change in various radiological parameters from preoperative period to postoperative period and at a follow up of two years.Methods: This was a prospective observational study conducted on 35 patients of either sex, in the age range of 18 months to 8 years, presenting to the paediatric orthopaedic OPD, of Artemis Health Institute, Gurgaon, Haryana, India between January 2012 and September 2014 in whom a diagnosis of acetabular dysplasia was made. All the patients underwent Dega transiliac osteotomy and the effectiveness of this osteotomy in the correction of acetabular dysplasia was assessed by measuring various radiological parameters preoperatively, postoperatively, and at a follow up of two years. The various radiological parameters included acetabular index (AI), centre edge angle of wiberg (CEAW), reimer’s extrusion index (REI) and the shenton’s line (SL).Results: In present study sample of 35 cases, 29 had DDH, 4 were secondary to cerebral palsy and 2 had developed dysplasia following septic arthritis of the hip. The sex distribution showed 19 females and 16 male patients. All the patients underwent Dega transiliac osteotomy at a mean age of 42.94±21.68 months. The mean value of AI improved from 42.43±4.77 degrees in preoperative period to 19.86±2.45 degrees at follow up. The mean value of CEAW improved from - 32.49±21.60 degrees in preoperative period to 32.06±5.48 degrees at follow up. The mean value of REI, improved from 91.06±21.43 % in preoperative period to 0.29±1.18 % at follow up. The SL was broken in all the 35 patients preoperatively, while at follow up it was continuous in all the patients. These changes in all the four parameters were statistically highly significant (p value<0.001).Conclusions: Thus results of present study demonstrate that Dega osteotomy is a safe, effective and versatile surgical procedure for the treatment of acetabular dysplasia secondary to DDH and other disorders. Since the majority of the patients included in this study had the diagnosis of DDH, the results of this study are more representative of dysplasia associated with DDH.

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