scholarly journals Hospitalizations and Emergency Department (ED) Visits after CAR-T Therapy - Real World Experience in Commercially Insured Patients

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 569-569
Author(s):  
Kelly Kenzik ◽  
P. Connor Johnson ◽  
Smita Bhatia
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Real World ◽  
Real World Data ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Underlying Malignancy ◽  
Car T ◽  
Ed Visits

Abstract Introduction: As a newly approved third line therapy for hematologic malignancies, chimeric antigen receptor (CAR)-T cell therapy can provide patients with a life-saving therapeutic option. CAR T-cell therapy carries risks of toxicities and potentially intensive health care use. However, given its relatively recent approval (approved in 2017), there is limited real world data on healthcare utilization after CAR-T cell infusion. We examined hospitalizations and ED visits for the first 12 mo after CAR-T cell infusion. Methods: We used Truven Health MarketScan database (one of the largest private health insurance claims datasets in the US) to identify commercially insured patients who received CAR-T cell infusion between Jan 2017 and Dec 2019 at age <65y. CAR-T cell therapy was identified using ICD-10 codes (Q2042, Q2041, 0540T, XW033C3, XW043C3) and national drug codes for axicabtagene ciloleucel and tisagenlecleucel. Patients were followed for hospitalizations and/or ED visits from CAR-T cell infusion to death, loss of coverage, 12 mo or 12/31/2019 (end of available data), whichever came first. The cumulative incidence of first hospitalization from CAR-T cell therapy was calculated using competing risks method. We also examined cumulative cause-specific hospitalizations per person-month at 30d, 31-90d, and >90d from infusion. Total number of ED visits and reasons for ED visits were examined by primary disease and by time from CAR-T cell infusion. Results: Overall, 204 patients (66% male) received CAR-T cell infusions (96% tisagenlecleucel) over the 3y period; median age at 1 st infusion was 55y (range 1-64). Cancer diagnoses included diffuse large B cell lymphoma (DLBCL, 62.8%), chronic lymphocytic leukemia (CLL, 12.3%), multiple myeloma (MM, 9.3%), other (15.6%). Median follow-up from CAR-T cell infusion was 3.2 mo (0-12); 11% were followed for all 12 mo. Hospitalizations: Ninety-one patients (44%) had 191 hospitalizations within 12 mo of CAR-T infusion (n=1: 47%, n=2: 24%, n >2: 28.5%); 16% of all CLL patients 12% of all DLBCL and 11% of all MM patients had >2 hospitalizations. Most prevalent reasons for hospitalization included infection (n=79; 41.3% of hospitalizations), myelosuppression (n=38; 19.9%), and management of underlying malignancy (n=35; 18.3%). The average length of stay per hospitalization was highest for infection (13.5d), followed by management of underlying malignancy (8.3d), and myelosuppression (5.9d). The cumulative incidence at 12 mo for cause-specific hospitalizations included: infection (22.2%), myelosuppression (11.9%), and managing malignancy (9.8%) (Fig 1). Overall, this cohort experienced 0.2 hospitalizations/person-mo. The majority of these hospitalizations occurred within the 1 st mo following CAR-T cell therapy (0.6/person-mo), declining to 0.11/person-mo at 31-90d, and to 0.04/person-mo at >90d (Fig 2). Infection and myelosuppression remained the most common reasons for hospitalizations across the three time periods. There were no statistically significant factors predicting hospitalization in multivariable models. ED visits: Fifty patients (25%) had 71 ED visits after CAR-T cell infusion (n=1: 76%; n=2: 14%; n>2: 10%). Reasons for ED visits included infections (n=14, 19.7%), myelosuppression (n=11, 15.5%), and cardiac emergencies (n=6, 8.5%). Median time to ED was 107d (range 8-355d). Nine ED visits occurred within the 1 st mo after CAR-T cell infusion (infection, epigastric/chest pain, thrombosis/hemorrhage [n=2 each], neutropenia, altered mental status, primary disease [n=1 each]). Conclusion: Real world data show that over the first 12 mo. after CAR-T cell therapy, 44% of the patients are re-hospitalized one or more times and 25% are seen in the emergency room. Infection is the most common reason for unplanned visits (hospitalizations or ED visits), followed by myelosuppression. The probability of these hospitalizations is highest within the first month, declining rapidly thereafter. These findings can be used to inform management strategies to mitigate unplanned healthcare utilization. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Real-World Experiences of CAR T-Cell Therapy for Large B-Cell Lymphoma: How Similar Are They to the Prospective Studies?

2021 ◽  
Vol 4 (3) ◽  
pp. 150-159
Author(s):  
Kevin Tang ◽  
Loretta J. Nastoupil
Keyword(s):  
Clinical Trials ◽  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
Real World ◽  
Response Rates ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

ABSTRACT Chimeric antigen receptor (CAR) T cell therapy has emerged as a revolutionary treatment option for highly aggressive B cell malignancies. Clinical trials of CD19 CAR T cells for the management of relapsed and/or refractory non-Hodgkin lymphoma (NHL) have shown markedly improved survival and response rates. The goal of this review is to evaluate whether the results from these clinical trials are reflective of real-world practices through the analysis of published literature of the commercially available CAR T cell products. We have found that despite the significantly different patient characteristics, the adverse events and response rates of real-world patients were similar to those of the clinical trials. Of interest, several groups excluded from the clinical trials, such as patients with HIV infection, chronic viral hepatitis, and secondary CNS (central nervous system) lymphoma, had case reports of promising outcomes.

Real-world adverse events associated with CAR T-cell therapy among adults age ≥ 65 years

2020 ◽  
Author(s):  
Marjorie E. Zettler ◽  
Bruce A. Feinberg ◽  
Eli G. Phillips Jr ◽  
Andrew J. Klink ◽  
Sonam Mehta ◽  
...  
Keyword(s):  
T Cell ◽  
Adverse Events ◽  
Cell Therapy ◽  
Real World ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

scholarly journals Patterns of leukocyte recovery predict infectious complications after CD19 CAR-T cell therapy in a real-world setting

2021 ◽  
Vol 0 ◽  
pp. 0-0
Author(s):  
Astha Thakkar ◽  
Zhu Cui ◽  
Stephen Zachary Peeke ◽  
Nishi Shah ◽  
Kith Pradhan ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Real World ◽  
Infectious Complications ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Real World Setting ◽  
Car T Cell Therapy ◽  
Car T

scholarly journals Real-World Treatment of Patients with Large B-Cell Lymphoma in the United States with Chimeric Antigen Receptor T-Cell Therapy

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4096-4096
Author(s):  
Kristin M. Zimmerman Savill ◽  
Andrew J Klink ◽  
Djibril Liassou ◽  
Dhruv Chopra ◽  
Jalyna Laney ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Real World ◽  
T Cell Therapy ◽  
Cell Therapies ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
The Us ◽  
Trial Setting

Abstract Introduction: The advent of chimeric antigen receptor (CAR) T-cell therapy has represented one of the most innovative therapeutic advances in oncology in recent years. Impressive clinical responses to CAR T-cell therapy observed in patients in clinical trials have led to the Food and Drug Administration (FDA) approval of five CAR T-cell therapies in the US since 2017 to treat large B-cell, mantle cell, and follicular lymphomas, as well as acute lymphoblastic leukemia (ALL) and multiple myeloma. The first two CAR T-cell therapies approved by the FDA, axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel), have now been on the US market for the treatment of patients with large B-cell lymphoma (LBCL) since 2017 and 2018, respectively, allowing for assessment of their use in real-world clinical practice. Given the complex logistics of the manufacturing, distribution, administration and unique toxicity of CAR T-cell therapies, initial use was limited to larger centers with prior experience with CAR T-cell therapy clinical trials. With greater use and availability of multiple CAR T-cell therapies, real-world evaluation of the clinical profiles, treatment patterns, and outcomes of LBCL patients treated with CAR T-cell therapies may inform clinical, regulatory, and drug development decision making, ultimately helping to improve patient outcomes. This real-world claims-based study aimed to describe characteristics and treatment outcomes of patients with diffuse LBCL (DLBCL) treated with the CAR T-cell therapies axi-cel or tisa-cel in the non-trial setting. Methods: Patients with at least 1 claim for axi-cel or tisa-cel made prior to 03/31/21 and a diagnosis code of DLBCL were identified from the Symphony Integrated Dataverse (IDV), a large US claims database containing linked longitudinal prescription, medical, and hospital claims. The IDV contains claims for 280 million active unique patients representing over 63% of prescriptions with full lifecycle data, 62% of medical claims, and 25% of hospital claims volume in the US. Patients were excluded from analysis if axi-cel or tisa-cel was the first therapy identified for the patient since diagnosis of DLBCL within the claims database, if treatment was received as a part of a clinical trial, if there were no supporting claims around CAR T-cell therapy in the claims database, if next line of therapy was received within 30 days of a sole claim for axi-cel or tisa-cel, or if data supported a diagnosis of ALL. Patient characteristics and treatment patterns were summarized using descriptive statistics. Results: Among a total of 88 eligible patients with DLBCL identified in this study, 52% (n=46) received axi-cel and 48% (n=42) received tisa-cel. At the time of treatment with axi-cel or tisa-cel therapy, median patient age was 63 years (range, 20-78 years) and commercial insurance was the primary payer for 83% of patients (n=73). The majority (n=59, 67%) of patients were male. Patients with DLBCL treated with axi-cel or tisa-cel were distributed across each of the 4 US census regions, with 27% from the Northeast, 11% from the South, 32% from the Midwest, and 30% from the West. . Axi-cel or tisa-cel was received a median of 14 months following patients' initial diagnosis of DLBCL and for the majority (n=54, 61%) of patients, axi-cel or tisa-cel-related claims were associated with administration of CAR T-cell therapy in the outpatient setting (Table). Prior to axi-cel or tisa-cel, 57% of patients (n=50) received 2 or more lines of systemic therapy. Within a median follow-up period of 7.8 months, 17% of patients (n=15) received systemic therapy following axi-cel or tisa-cel treatment. Conclusions: In the first few years of US market availability, the CAR T-cell therapies axi-cel and tisa-cel have been used to treat patients with LBCL outside of the clinical trial setting. While the majority of patients in this real-world claims-based study received axi-cel or tisa-cel in an outpatient setting, hospital claims are underrepresented in the database utilized. Despite short follow-up (less than 8 months from initiation of these CAR T-cell therapies), approximately one in 6 patients appear to have relapsed disease, based on the need for subsequent systemic therapy. Further research is warranted to understand real-world clinical outcomes among patients treated with CAR T-cell therapy outside the trial setting. Figure 1 Figure 1. Disclosures Zimmerman Savill: Roche/Genentech: Ended employment in the past 24 months; Cardinal Health: Current Employment. Klink: Cardinal Health: Current Employment, Current holder of stock options in a privately-held company. Liassou: Cardinal Health: Current Employment. Chopra: Cardinal Health: Current Employment. Laney: Cardinal Health: Current Employment. Gajra: Cardinal Health: Current Employment, Current equity holder in publicly-traded company.

scholarly journals Neurological Adverse Events Following CAR-T Cell Therapy: A Real-World Analysis of Adult Patients Treated with Axicabtagene Ciloleucel or Tisagenlecleucel

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1952-1952 ◽  
Author(s):  
Ajeet Gajra ◽  
Marjorie E Zettler ◽  
Eli G Phillips Jr. ◽  
Andrew J Klink ◽  
Jonathan K. Kish ◽  
...  
Keyword(s):  
Clinical Trials ◽  
T Cell ◽  
Adverse Events ◽  
Cell Therapy ◽  
Real World ◽  
Case Reports ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Introduction: Neurotoxicity is a major adverse event (AE) of CAR-T therapy with diverse presentation. When severe, it can be fatal, and may lead to neurologic sequelae as well as contribute to increased health care utilization, driving up cost of therapy. In clinical trials, the most common neurologic AEs with axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tis-cel) included encephalopathy, headache, tremor, dizziness, aphasia, delirium, insomnia and anxiety. Fatal and serious cases of cerebral edema, leukoencephalopathy and/ or seizures have been reported with both agents. In this real-world analysis, we reviewed post-marketing case reports from the FDA Adverse Events Reporting System (FAERS). Database involving axi-cel or tis-cel for large B cell lymphoma (LBCL), with the dual objectives of characterizing the various components of neurotoxicity and assessing the association of neurological (neuro) AEs with demographic and treatment factors as well as with other AEs reported with CAR-T cell therapy use. Methods: The FAERS database contains anonymized reports of product-related AEs, classified using the Medical Dictionary for Regulatory Activities (MedDRA) and categorized as serious or non-serious. The FAERS database was queried for cases involving axi-cel or tis-cel (and their respective trade names) from the FDA approval date for the LBCL indication (October 18, 2017 for axi-cel; May 1, 2018 for tis-cel) through March 31, 2019. Cases were excluded if patient age was unknown or if the case was reported outside the US. Of all patients reported to have neuro AEs, the frequency of various components was collected. The association of neuro AEs with patient age, concomitant AEs and key lab abnormalities were evaluated by Fisher's exact test, using a two-sided α=0.05 to determine statistical significance. Median age in each subgroup was compared using the Mann-Whitney U test. Results: In the 397 case reports identified, the majority of reactions (376, 95%) were classified as serious. Overall, 258 (65%) were reported to have neuro AEs, with "neurotoxicity" reported in 170 cases (66%); encephalopathy including CAR-T cell-related, metabolic and toxic in 92 cases (36%); seizures including status epilepticus, myoclonus and partial seizures in 12 cases (5%); stroke including cerebrovascular accident, hemiparesis, basal ganglia, brain stem, cerebellar and cerebral infarcts, motor dysfunction, facial and cranial nerve paralysis in 13 cases (5%); speech disorders including terms of aphasia, dysarthria, speech and language impairment in 55 cases (21%); amnesia and memory impairment in 18 cases (7%); brain or spinal cord edema and increased intracranial pressure in 6 cases (2%). Peripheral neuropathy was reported in 5 cases (2%). Symptoms of headache, tremors, dizziness and somnolence were reported in 30 (12%), 41 (16%) 3 (1%) and 34 (13%) cases respectively. Confusional state, delirium or agitation were reported in 61 cases (24%). Neuro AEs were associated with use of axi-cel vs. tis-cel (69% vs. 24%, p <0.01) and with age ≥65 years (43% vs. 36% in age <65, p=0.02) but did not impact death or hospitalization (Table). Neuro AEs were associated with cytokine release syndrome (CRS, 67% vs. 49% without, p<0.01) as well as with cardiac AEs including tachycardia (p<0.01). There was an association of psychiatric AEs with neuro AEs though some (delirium, agitation, hallucination) may be considered a part of the neuro AEs. There were no associations of febrile neutropenia, thrombocytopenia, serum ferritin and C-reactive protein with neuro AEs (all p values>0.05). Conclusions: Neuro AEs were common with CAR-T cell therapy in the real world and largely resembled those reported in clinical trials. Neuro AEs were associated with the agent used, age ≥65 as well as the presence of CRS, cardiac and psychiatric AEs but not with any of the laboratory values studied. The limitations of this study include its retrospective nature, potential under-reporting to FAERS and the relatively small number of patients in the tis-cel group due to its later approval and shorter time available for uptake compared to axi-cel. Despite these limitations, our findings can serve to inform clinicians' decision making when treating adult patients with CAR-T cell therapy. Further research is needed to better discern the etiopathology and biomarkers of neuro AEs in CAR-T cell therapy. Disclosures Gajra: Cardinal Health: Employment. Zettler:Cardinal Health: Employment. Phillips Jr.:Cardinal Health: Employment. Klink:Cardinal Health: Employment. Kish:Cardinal Health: Employment. Mehta:Cardinal Health: Employment. Feinberg:Cardinal Health: Employment.

Real-World Analysis of Adverse Events Associated with CAR T-Cell Therapy Among Adults Age ≥65 Years

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1951-1951 ◽  
Author(s):  
Marjorie E Zettler ◽  
Bruce A Feinberg ◽  
Eli G Phillips Jr. ◽  
Andrew J Klink ◽  
Sonam Mehta ◽  
...  
Keyword(s):  
T Cell ◽  
Adverse Events ◽  
Cell Therapy ◽  
Real World ◽  
Age Group ◽  
T Cell Therapy ◽  
Younger Patients ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Introduction: Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tis-cel) are chimeric antigen receptor (CAR) T-cell therapies that target CD19-expressing B cells. Both therapies have been approved by the United States (US) Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory large B-cell lymphoma (LBCL) after at least 2 lines of systemic therapy. The median age at diagnosis of diffuse LBCL is 66 years, with over half the cases occurring in patients over age 65. Patients >65 years have worse survival than younger patients. Despite this predilection for older age, only one quarter of the patients in the pivotal trials supporting approval of the 2 therapies were age 65 or older. An analysis of the safety of axi-cel in the pivotal ZUMA-1 trial showed no significant differences between the age <65 and ≥65 subgroups; however, the small number of older patients included on the original clinical trials due to the constraints of the stringent eligibility criteria limits the generalizability of these findings (Sano et al, Blood 2018 132:96). In this analysis, we reviewed post-approval adverse events (AEs) involving axi-cel or tis-cel for LBCL and compared reactions and outcomes by age utilizing the FDA Adverse Events Reporting System (FAERS) Database, which was created to support FDA's post-marketing safety surveillance program for drug and therapeutic biologic products. Methods: The FAERS database contains anonymized reports of product-related AEs, classified using the Medical Dictionary for Regulatory Activities (MedDRA) and categorized as serious or non-serious. The database was queried for cases involving axi-cel or tis-cel (and their respective trade names) from the FDA approval date for the LBCL indication (October 18, 2017 for axi-cel; May 1, 2018 for tis-cel) through March 31, 2019. Cases were excluded if the age of the patient was unknown. Cases reported outside the US were excluded. Patient characteristics and adverse events were summarized using descriptive statistics. Comparisons of rates of AEs by age group were made using Fisher's exact test; statistical significance was determined at a two-sided α=0.05. Results: A total of 397 cases were retrieved (360 involving axi-cel, 37 involving tis-cel). The median age of the patients involved was 62 years (range 18-81), with 153 (39%) of the patients age 65 or older. The vast majority of reactions (376, 95%) reported to FAERS were classified as serious. Overall, 141 (36%) cases resulted in hospitalization; 33 (8%) cases had an outcome categorized as life-threatening; 46 (12%) cases resulted in death; 6 (2%) resulted in disability. The most common reaction in each age group was cytokine release syndrome (CRS), reported in 64% and 56% of patients <65 and ≥65 groups, respectively (Table). When a composite definition for CRS was utilized by including individual clinical features that comprise CRS, a higher proportion of patients <65 were noted to have CRS (80% vs. 67%, p<0.01). Pyrexia (41% vs. 24%, p<0.01), tachycardia (17% vs. 8%, p=0.01), hospitalization (42% vs. 25%, p<0.01) and elevated ferritin levels (3% vs. 0%, p=0.03) were significantly more common among the younger age group. Patients ≥65 had a significantly higher proportion of cases of neurotoxicity (50% vs. 39%, p=0.04); atrial fibrillation was also reported more frequently in the older age group compared to younger patients (8% vs. 3%, p=0.02). Conclusions: This large-scale post-marketing report of CAR T-cell therapy associated AEs in the real world suggests differences based on age: patients ≥65 had a higher incidence of neurotoxicity and atrial fibrillation while younger patients had increased incidence of some CRS components, especially pyrexia and tachycardia. There was no demonstrable difference in deaths between the 2 groups, but younger patients had higher rates of hospitalization. This report provides real-world evidence for use of CAR T-cell therapy in patients ≥65 and can inform clinical care based on patterns of AEs observed. Potential under-reporting of cases to the FAERS database, the retrospective design of this study and limited data available in the case reports preclude interpretation of causality. Despite these limitations, our findings identified real-world trends in reported signals that complement clinical trial safety data and support further pharmacoepidemiologic study. Disclosures Zettler: Cardinal Health: Employment. Feinberg:Cardinal Health: Employment. Phillips Jr.:Cardinal Health: Employment. Klink:Cardinal Health: Employment. Mehta:Cardinal Health: Employment. Gajra:Cardinal Health: Employment.

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