QIM19-136: Developing an Ideal CAR-T Cell Therapy Patient Experience Through Human-Centered Design and Innovation

2019 ◽  
Vol 17 (3.5) ◽  
pp. QIM19-136 ◽  
Author(s):  
Allison Matthews ◽  
Surbhi Sidana ◽  
Lauren Seymour ◽  
Nancy Pick ◽  
James Pringnitz ◽  
...  
Keyword(s):  
Patient Experience ◽  
Care Delivery ◽  
Design Team ◽  
Patient Journey ◽  
Human Centered Design ◽  
T Cell Therapy ◽  
Evaluation Phase ◽  
Patient Reported ◽  
Car T ◽  
The Impact

Background: The patient/caregiver experience during CAR-T therapy is stressful, overwhelming, terrifying, and often a patient’s last treatment option. The Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery Innovation and Design team has worked with the CAR-T therapy clinical team to develop a patient experience that provides patients with a sense of caring, supportive environment, timely knowledge, and realistic expectations. Using a human-centered design approach, the Innovation and Design team worked with patients and caregivers to understand latent and unspoken needs in order to develop an ideal CAR-T therapy patient journey. Methods: With qualitative interviewing techniques, patient observation, and low fidelity experimentation, 21 patients/caregiver pairs were interviewed throughout their CAR-T therapy experience in 2018. Patients were interviewed at several touch points as well as encouraged to reach out to the Innovation and Design team at any point with reflections on their experiences. Patients were recruited as they began their evaluation phase for CAR-T therapy. The interviews were unscripted to allow for a breadth of discovery by not constraining the conversations to previously developed themes. As themes emerged from patient/caregiver interviews, artifacts and interventions were designed to alleviate pain points and improve the patient/caregiver experience. These artifacts and interventions were integrated into the clinical processes in real time and patient/caregivers were interviewed to understand the impact of these activities. Results: Several themes emerged from qualitative interviews with patients and caregivers. From the themes, interventions were developed. We were able to demonstrate a qualitative improvement in patient/caregiver experience through these interventions (Figure 1). Conclusions: Patients/caregivers undergoing CAR-T therapy have unique issues surrounding the logistics of care, emotional burden, and physical effects of treatment. We implemented processes to address these issues and observed a qualitative improvement via patient interviews/feedback. Ongoing work includes optimizing remote monitoring, digital platforms for patient education, and a quantitative study looking at patient reported outcomes (PROs) in such patients. To our knowledge, this is the first report for care delivery optimization in real-world practice for this new therapy.

Emerging trends and utilization of patient-reported outcomes (PROs) in clinical trials of chimeric antigen receptor (CAR) T-cell therapies.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19142-e19142
Author(s):  
Anthony John Messina ◽  
Vasily Andrianov ◽  
Daniel Mazzolenis ◽  
Liat Vidal-Fisher
Keyword(s):  
Clinical Trials ◽  
T Cell ◽  
Phase I ◽  
Patient Reported Outcomes ◽  
Utilization Rate ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Patient Reported ◽  
Car T ◽  
The Impact

e19142 Background: Patient-reported outcomes (PROs) are an important tool to assess the impact of new therapies on health-related quality of life (HRQoL). This study aimed to describe if and what PRO instruments are currently being utilized in CAR-T cell therapy studies in solid and hematological malignancies while assessing the patterns of inclusion and trends of HRQoL data reporting. Methods: We used Citeline to search for clinical trials between Jan 2008 - Jan 2020, excluding planned or terminated studies, non-oncology, non-treatment, and duplicates. Reviewers extracted various parameters for included trials, then cross-matched data with EU Clinical Trials Register, Clinical trials.gov, trial protocols (when available), and Google. The reporting of PRO data was then assessed for those Closed/Completed trials that included a PRO via PubMed/MEDLINE, Sponsor, and Google. Results: A sample of 664 CAR-T trials was identified. PROs were included in only 6.17% (41/664) studies. Of the 41 trials that included a PRO, 63.41% (26/41) utilized more than one PRO, with the generic EORTC QLQ-C30 and the EQ-5D being used predominately. Median HRQoL follow-up was 5-years on most trials. No studies used PROs as primary endpoints. The majority of PROs were observed to be utilized in early phase trials (phase I, 12; Phase I/II, 17). PROs were first incorporated in CAR-T trials beginning in 2014, and the utilization rate has increased steadily, except for 2019. PROs were included in 3 first line trials, 22 second line, 5 third line, and 11 fourth line or greater. PRO utilization between solid tumor trials and hematologic malignancies was comparable (6.04% [9/149], and 6.26% [32/511]). Of the completed/closed trials, 28.57% (3/14) published PRO data and met at least eight of the CONSORT-PRO quality indicators. Conclusions: The utilization of PROs in CAR-T trials (6.17%) is under the industry average of 27%, despite the growing importance of HRQoL and its impact on value-based care. The findings from this review reflect the overall increased attention to CAR-T as a new therapeutic entity and the continued deficiency of including and reporting of PROs in trial designs.

Vaccine titers in lymphoma patients receiving chimeric antigen receptor T-cell therapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7555-7555
Author(s):  
Radhika Bansal ◽  
Paschalis Vergidis ◽  
Pritish Tosh ◽  
John W. Wilson ◽  
Matthew Hathcock ◽  
...  
Keyword(s):  
T Cell ◽  
Hepatitis B ◽  
Cell Therapy ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Aggressive Lymphoma ◽  
Cell Transplant ◽  
T Cell Therapy ◽  
Car T ◽  
The Impact

7555 Background: While CAR-T therapy is not myelo-ablative, patients with aggressive lymphoma treated with CD19 chimeric antigen receptor T cell therapy (CAR-T) are lymphodepleted and have prolonged B cell aplasia. The impact of CAR-T on immunologic protection from vaccine-preventable diseases (and thus the need to revaccinate) is not known. We report the vaccine titers of patients treated with axicabtagene ciloleucel (axi-cel) at Mayo Clinic. Methods: Retrospective chart review of adult lymphoma patients who received axi-cel from 9/2018 to 9/2020 for anti-viral and anti-bacterial titers prior to CAR-T infusion and at month 3 (MO3) post CAR-T. Results: Prior to CAR-T therapy, positive titer rate was highest for tetanus and lowest for Strep pneumoniae (Strep PNA) (Table). Similar trends were seen whether patients had stem cell transplant (ASCT) within 2 years of CAR-T (i.e. within immunization timeframe post ASCT) or not (Table). Compared to patients who had ASCT, those who did not had higher rate of positive titer for Strep PNA and lower rate for hepatitis B, Mumps, and VZV. The same trend for sero-positive rate were observed at MO3 post CAR-T. Patients with IgG<400 mg/dl received IVIG supplement for prophylaxis. Among the 23 patients who received IVIG, variable rate of conversion from negative to positive titers were seen for measles (1/2, 50%), mumps (2/3, 67%), rubella (2/3, 67%), varicella-zoster (VZV, 3/3, 100%), hepatitis A (6/6, 100%), hepatitis B (6/7, 86%) and Strep PNA (0/10, 0%). For patients who did not receive IVIG prophylaxis, there was one loss of seropositivity for Strep PNA (1/4, 25%). Conclusions: The presence of protective vaccine titers is variable for patients receiving CAR-T, regardless of recent ASCT. The loss of protective titers post CART was low. IVIG variably impacted vaccine titer status. Immunization remains important for patients with ASCT prior to CART, without completion of post ASCT immunization protocol. Further study is needed to inform the need for immunization and optimal timing post CART.[Table: see text]

scholarly journals Understanding the impact of a new Pharmacy Sore throat Test and Treat service on patient experience: A quantitative study

2020 ◽  
Author(s):  
Efi Mantzourani ◽  
Rebecca Cannings-John ◽  
Andrew Evans ◽  
Haroon Ahmed ◽  
Alan Meudell ◽  
...  
Keyword(s):  
Sore Throat ◽  
Patient Experience ◽  
Point Of Care ◽  
Free Text ◽  
Health Seeking Behaviour ◽  
Health Seeking ◽  
Future Health ◽  
Test And Treat ◽  
Patient Reported ◽  
The Impact

Abstract Background : A pilot of the first NHS funded Sore Throat Test and Treat (STTT) service in the United Kingdom began in selected community pharmacies in Wales in November 2018. The aim of this research was to explore whether a pharmacist delivering consultation for sore throat that included clinical scoring and point-of-care testing was acceptable to patients, and how this might influence future health-seeking behaviour for subsequent sore-throats. Methods : Quantitative research was employed, with a non-experimental design using a survey research tool including a mix of closed and open questions, developed in collaboration with members of the public. The patient experience survey was distributed to all patients who had completed a consultation between November 2018 and May 2019. Data from completed surveys were entered in Jisc Online Surveys® and exported to Excel® for descriptive statistics. Free-text comments were analysed using content and inductive thematic analysis. Results : A total of 510 surveys were received from 2,839 sore throat consultations (response rate 18%). Overall, 501 patients (98%) were satisfied with the service. Patients’ confidence in managing their condition and service satisfaction was not dependent on having been supplied antibiotics. A total of 343 patients (67%) requested a GP appointment but were offered to a consultation in the pharmacy. After the service, 504 patients (99%) stated that they would return to the pharmacy for subsequent sore throat symptoms. Inductive analysis of free-text comments (n=242) revealed 3 themes: convenience and accessibility; professionalism of pharmacy team; and perceived value of the service. Conclusions : Results confirmed high levels of patient satisfaction with the new service, the way it was delivered and the increased choice of options for sore throat symptom management it offered. Whilst this research can only discuss patients’ reported future behaviour, the patient-reported stated intentions signify a potential shift in health-seeking behaviour towards a pharmacist-led service. This has important implications in supporting the long term plan of the governments in Wales and England to redirect management of uncomplicated conditions from GPs to pharmacies.

scholarly journals Decreased Rates of Severe CRS Seen with Early Intervention Strategies for CD19 CAR-T Cell Toxicity Management

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 586-586 ◽  
Author(s):  
Rebecca Gardner ◽  
Kasey J Leger ◽  
Colleen E. Annesley ◽  
Corinne Summers ◽  
Julie Rivers ◽  
...  
Keyword(s):  
T Cells ◽  
Early Intervention ◽  
T Cell ◽  
T Cell Therapy ◽  
Clinical Criteria ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
The Impact

Abstract Introduction: CD19 CAR-T cell therapy is a promising strategy in the treatment of pre-B ALL, with early phase trials showing results of >90% CR rates. Over 90% of patients develop CRS concurrent with proliferation of CAR-T cells. Rates of severe CRS (sCRS) in previously reported studies have ranged from 23% to 43%. Concerns have been raised that the use of immunomodulation may impact engraftment and proliferation of CAR-T cells, potentially impairing efficacy. Additionally, concern has been raised that the use of tocilizumab (toci) may lead to an increased risk of neurotoxicity. Here we report our clinical experience with early treatment of CRS in a cohort of patients who received pre-emptive toci and dexamethasone (dex) with the goal to lessen the occurrence of sCRS. Methods: Subjects enrolled on the PLAT-02 study (NCT02028455) underwent apheresis and CAR-T cell manufacturing followed by lymphodepletion and CAR-T cell infusion. In this phase 1 dose escalation study, subjects were treated from 0.5- 10 x 106 CAR T cells/kg. sCRS included the use of pressors or inotropes. Severe neurotoxicity included any grade 3/4 neurotoxicity, excluding headache, and grade≥ 2 seizure. The first 23 subjects received toci (8mg/kg) with or without steroids for dose limiting toxicity (DLT). Subsequently the protocol was modified to provide guidelines for early intervention with CRS. The next 20 subjects received toci and subsequent dex (5-10mg every 6-12 hours prn) for persistent symptoms using clinical criteria, with the goal to prevent sCRS. Clinical criteria included persistent fever of ≥ 39°C despite antipyretics for 10 hours, persistent/recurrent hypotension after initial fluid bolus, and initiation of oxygen supplementation. Engraftment of CAR T cells and B cell aplasia was determined by flow cytometry Results: The two cohorts had similar overall rates of CRS: 91% (21/23) vs 95% (19/20), with higher rates of sCRS in the initial cohort: 30% (7/23) vs 15% (3/20) (p=0.3). Neurotoxicity was seen in 48% v 50% with similar rates of severe neurotoxicity, 22% v 25%. In the first cohort of subjects, 22% (5/23) received toci and 17% (4/23) received steroids due to DLT. In the second cohort, there was an increase in the number of subjects receiving toci to 50% (11/20, p=0.032) with an increase in steroid use as well to 30% (6/20, p=0.5) The overall rate of MRD-negative CR in this study was 93% (40/43) and this was not impacted by the use of toci or dex. The rate of MRD-negative CR in those subjects receiving toci without steroids, toci with steroids, and steroids alone were also similar (89% vs 100% vs 100%). Additionally the MRD-negative CR rate in the first cohort was similar to the early intervention cohort (91% v 95%). Continued peripheral blood expansion of CAR+ T cells can be seen in subjects who have received tocilizumab and/or steroids. There were no differences detected among the immunomodulatory groups with regards to peak percentage engraftment, area under the curve, or functional persistence of CAR T cells. Conclusions: Despite encouraging efficacy, the toxicity associated with CD19 CAR-T cell therapy gives rise to concerns about its widespread use. Early intervention with immunomodulation appears to decrease the rates of sCRS while preserving the high rates of MRD-negative CR. Additionally, the engraftment and persistence of CAR+T cells is not impacted by the use of toci and/or steroids when given early after the onset of clinical symptoms of CRS. Although not intended to assess the impact of toci on neurotoxicity, it is of note that the rates of neurotoxicity, and in particular severe neurotoxicity, did not increase. These results warrant further study of the impact of early immunomodulation for the prevention of sCRS. Disclosures Gardner: Amgen: Honoraria. Li:Juno Therapeutics: Employment, Equity Ownership. Jensen:Juno Therapeutics, Inc: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding.

The impact of telemedicine on patient-reported outcomes in urologic oncology.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e14154-e14154
Author(s):  
Adam John Gadzinski ◽  
Isabelle O. Abarro ◽  
Blair Stewart ◽  
John L. Gore
Keyword(s):  
Travel Time ◽  
Cancer Care ◽  
Patient Reported Outcomes ◽  
Care Delivery ◽  
Testis Cancer ◽  
Urologic Oncology ◽  
Time Costs ◽  
Patient Reported ◽  
The Impact ◽  
Travel Burden

e14154 Background: Nearly 20% of Americans live in rural communities. These individuals face barriers to accessing cancer care, including prevalent poverty and substantial travel burden to seeing cancer providers. We aimed to assess the impact of a rurally focused telemedicine program on patient outcomes in our urologic oncology outpatient clinic. Methods: We prospectively identified patients from rural Washington State, or who lived outside Washington, with a known or suspected urological malignancy being evaluated at the University of Washington Urology Clinic via an in person clinic or a telemedicine appointment. Patients were invited to complete a post-visit survey that assessed satisfaction, travel time, costs, and work absenteeism. We compared patient-reported outcomes between those seen as in-person versus telemedicine visits. Results: We invited 291 eligible patients from June 2019 – February 2020 to participate, 140 patients (48%) completed the survey. One-hundred and thirty-three patients had in person visits and 7 had telemedicine visits. Median age was 68, male 86%, and 69% Caucasian. Eighty-seven patients (62%) were from rural Washington; the remainder resided out-of-state. Patients were being evaluated for prostate cancer (57%), kidney cancer (18%), urothelial cancer (24%), and testis cancer (1%). Patient-reported outcomes are displayed in Table. Seventeen patients coming for in-person visits (13%) paid ≥ $1000 in total travel costs. No differences were noted in patient satisfaction. Conclusions: Patients traveling to our clinic from out-of-state and rural Washington incur significant travel time, costs, and time away from work to receive outpatient urologic cancer care. Telemedicine provides a medium for cancer care delivery that eliminates the significant travel burden associated with in person clinic appointments. [Table: see text]

Outpatient practice pattern and remote patient monitoring for axicabtagene ciloleucel CAR-T therapy in patients with aggressive lymphoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7554-7554
Author(s):  
Radhika Bansal ◽  
Jonas Paludo ◽  
Adam Holland ◽  
Spychalla Megan ◽  
McClanahan Alli ◽  
...  
Keyword(s):  
Median Time ◽  
Patient Monitoring ◽  
Vital Signs ◽  
Aggressive Lymphoma ◽  
Remote Patient Monitoring ◽  
T Cell Therapy ◽  
Early Admission ◽  
Patient Reported ◽  
Car T ◽  
Remote Patient

7554 Background: Chimeric antigen receptor T-cell therapy (CAR-T) are commonly administered inpatient due to concern for early onset cytokine release syndrome (CRS), especially with axicabtagene ciloleucel (axi-cel). We report Mayo Clinic Rochester experience for hospital-based outpatient (HBO) management of patients (pts) receiving axi-cel and identify opportunities for improvement. HBO is closely integrated with inpatient practice and includes the same specialty trained clinical team. It is the first point of contact 24/7 for pts and triage evaluations. Lymphodepletion chemotherapy and CAR-T infusion is given on HBO followed by daily monitoring till day 8 and thereafter, as clinically needed until admission criteria is met. Methods: We retrospectively analyzed database of pts who received axi-cel between 1/2018 and 1/2021. After 06/2020, remote patient monitoring (RPM) tools were implemented to collect patient-reported neurologic symptoms and vital signs via bluetooth-enabled devices 4 times daily through month 1. Adverse data trends are addressed by the HBO team. Results: Among 72 recipients, 89% received their cells outpatient; 8% remained outpatient for the entire month. CRS and neurotoxicity incidence were comparable to those reported from CIBMTR. Median time to first admission was 2 days (Table). Use of bridging therapy, increased CRP and LDH were associated with early admission (≤3 days). Median time to tocilizumab, steroid, oxygen support, vasopressor was 4 days after admission. Half of HBO visits required intervention such as blood transfusions, IV medications through the first month. Nine pts had enrolled in RPM to date; with 8 having evaluable data. With 4 scheduled entries/day, a median of 1 entry/day was skipped and 2 entries/day were answered incompletely. An average of 57 additional unscheduled entries were generated per pt. Among a median of 373 (range 91-522) readings per pt over the first month, 4% (2%-20%) of the readings generated alerts. An average of 4 alerts were seen within 48 hours prior to admission. Data including additional subjects will be presented at ASCO meeting. Conclusions: We report a feasible outpatient care model for management of axi-cel recipients with safe outcomes. Clinical characteristics associated with more aggressive disease are associated with likelihood of early admission. Early RPM experience suggest use of digital tools could improve monitoring compliance and may predict evolution to symptoms requiring escalation of care.[Table: see text]

The impact of telemedicine on patient-reported outcomes in urologic oncology.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 200-200
Author(s):  
Adam John Gadzinski ◽  
Isabelle O. Abarro ◽  
Blair Stewart ◽  
John L. Gore
Keyword(s):  
Travel Time ◽  
Cancer Care ◽  
Patient Reported Outcomes ◽  
Care Delivery ◽  
Testis Cancer ◽  
Urologic Oncology ◽  
Time Costs ◽  
Patient Reported ◽  
The Impact ◽  
Travel Burden

200 Background: Nearly 20% of Americans live in rural communities. These individuals face barriers to accessing cancer care, including prevalent poverty and substantial travel burden to seeing cancer providers. We aimed to assess the impact of a rurally focused telemedicine program on patient outcomes in our urologic oncology outpatient clinic. Methods: We prospectively identified patients from rural Washington State, or who lived outside Washington, with a known or suspected urological malignancy being evaluated at the University of Washington Urology Clinic via an in person clinic or a telemedicine appointment. Patients were invited to complete a post-visit survey that assessed satisfaction, travel time, costs, and work absenteeism. We compared patient-reported outcomes between those seen as in-person versus telemedicine visits. Results: We invited 1453 eligible patients from August 2019–July 2020 to participate; 615 patients (42%) completed the survey. 198 patients had in person visits and 417 had telemedicine visits. Median age was 68, 89% were male, and 73% were white. 525 patients (85%) were from Washington; the remainder resided out-of-state. Patients were being evaluated for prostate cancer (62%), kidney cancer (14%), urothelial cancer (22%), and testis cancer (2%). Patient-reported outcomes are displayed in Table. Twenty-two patients coming for in-person visits (11%) paid ≥ $1000 in total travel costs. No differences were noted in patient satisfaction between in-person and telemedicine visit types. Conclusions: Patients traveling to our clinic from out-of-state and rural Washington incur significant travel time, costs, and time away from work to receive outpatient urologic cancer care. Telemedicine provides a medium for cancer care delivery that eliminates the significant travel burden associated with in-person clinic appointments. [Table: see text]

scholarly journals Do Gender-Predominant Primary Health Care Organizations Have an Impact on Patient Experience of Care, Use of Services, and Unmet Needs?

2017 ◽  
Vol 54 ◽  
pp. 004695801770968 ◽  
Author(s):  
Raynald Pineault ◽  
Roxane Borgès Da Silva ◽  
Sylvie Provost ◽  
Michel Fournier ◽  
Alexandre Prud’homme ◽  
...  
Keyword(s):  
Health Care ◽  
Primary Health Care ◽  
Patient Experience ◽  
Unmet Needs ◽  
Care Delivery ◽  
Care Organization ◽  
Experience Of Care ◽  
Primary Health ◽  
Use Of Services ◽  
The Impact

Physicians’ gender can have an impact on many aspects of patient experience of care. Organization processes through which the influence of gender is exerted have not been fully explored. The aim of this article is to compare primary health care (PHC) organizations in which female or male doctors are predominant regarding organization and patient characteristics, and to assess their influence on experience of care, preventive care delivery, use of services, and unmet needs. In 2010, we conducted surveys of a population stratified sample (N = 9180) and of all PHC organizations (N = 606) in 2 regions of the province of Québec, Canada. Patient and organization variables were entered sequentially into multilevel regression analyses to measure the impact of gender predominance. Female-predominant organizations had younger doctors and nurses with more expanded role; they collaborated more with other PHC practices, used more tools for prevention, and allotted more time to patient visits. However, doctors spent fewer hours a week at the practice in female-predominant organizations. Patients of these organizations reported lower accessibility. Conversely, they reported better comprehensiveness, responsiveness, counseling, and screening, but these effects were mainly attributable to doctors’ younger age. Their reporting unmet needs and emergency department attendance tended to decrease when controlling for patient and organization variables other than doctors’ age. Except for accessibility, female-predominant PHC organizations are comparable with their male counterparts. Mean age of doctors was an important confounding variable that mitigated differences, whereas other organization variables enhanced them. These findings deserve consideration to better understand and assess the impacts of the growing number of female-predominant PHC organizations on the health care system.

scholarly journals Associations between Socioeconomic Status and Bispecific LV20.19 CAR T-Cell Therapy Outcomes

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4084-4084
Author(s):  
Edward Paul Hackett ◽  
Nirav N. Shah ◽  
Cecilia Hillard ◽  
Elizabeth Aughey ◽  
Rachel Cusatis ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Research Funding ◽  
Low Ses ◽  
Therapy Outcomes ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Patient Reported ◽  
Car T

Abstract Background Socioeconomic Status (SES) is recognized as a major contributor to health disparities in overall disease rate, morbidity, mortality, and quality of life (QOL). Specifically, low SES, independent of race, has a negative impact on solid and haematological cancer outcomes. Chimeric antigen receptor (CAR) T-cell cancer therapy is an increasingly utilized novel treatment option for the treatment of lymphoma; however its use is associated with cytokine release syndrome (CRS), neurotoxicity (NTX), and QOL impairments. Though the precise mechanism for these toxicities is unknown, adverse effects of CAR T-cell therapy are associated with neuroinflammatory markers that are upregulated in low SES populations. In this study, we hypothesized that patient response to a novel anti-CD20 and anti-CD19 (LV20.19) CAR T-cell treatment is affected by patient SES. Our second goal was to explore several possible biological mechanisms of the effects of SES on CAR T-cell therapy outcomes, including cytokines and kynurenine metabolites. Methods The current study population (N=15) is derived from a parent study evaluating patients treated with LV20.19 CAR T-cells on a Phase I/Ib clinical trial (NCT03019055). Patients provided blood samples and patient reported outcome (PRO) data 15 days before therapy (baseline), Day 14 post therapy (D14), D28, and D90. Cytokines were sent to Eve Technologies and quantified using an ELISA. Our analysis focused on 10 cytokines associated with CAR T-cell therapy neurotoxicity. Tryptophan (TRP) and kynurenine metabolites were quantified from serum samples using stable isotope-dilution liquid chromatography/mass spectrometry of the daughter ions (LC-MS-MS). Neurotoxicity was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events v5 and CRS was graded using Lee et al. (Blood; 2019) PROs included depression and anxiety (Inventory of Depression and Anxiety), sleep (Pittsburgh Sleep Quality Index; PSQI), fatigue (Fatigue Symptom Inventory; FSI), and pain (Brief Pain Inventory; BPI) intensity (BPII) and interference (BPIF). SES was assessed by household annual income either above or below the Wisconsin median annual income in 2021 of $54,660 (high SES as &gt;$55,000, n=7; low SES as $10,001-55,000, n=8). SES groups were compared against therapy outcomes using Wilcox Ranked Sum test, Student's t-test, and mixed effects linear models with a random subject intercept and estimated marginal means, respectively. Results There was no significant difference between SES groups based on age, education, or clinical response to therapy by D28 (Table 1). Baseline LDH was 3.4-fold higher in low compared to high SES patients (p=0.04). Most peak cytokine concentrations were higher in low SES patients with significant elevations (p&lt;0.05) in G-CSF, I-309, IL-8, IP-10, MCP-2, and TNFa (9-fold, 3-fold, 3-fold, 2-fold, 2-fold, and 4-fold, respectively; Figure 1). Low SES patients also had significantly elevated neurotoxic pathway kyunerine metabolites (p&lt;0.05; Figure 2) 3-hydroxyanthranilate (3-HAA) at D28 (8-fold) and quinolinic acid (QA) at baseline (5-fold), D14 (8-fold), and D28 (6-fold). Though incidences of CRS were only qualitatively higher in low SES patients (p=0.07), low SES patients experienced CRS significantly earlier (p=0.009; Table 2). Not enough patients experienced NTX for sufficient analysis. Patients with low SES indicated more pain intensity on D90 (BPII; p=0.021) and baseline pain interference (BPIF; p=0.08; Figure 3). Low SES patient reported worse sleep quality at D90 than high SES patients (p&lt;0.05), and low SES average was higher than the PSQI threshold for "poor sleep" (5) at baseline, D28, and D90. Conclusion Our data show preliminary evidence that SES is associated with biological and clinical outcomes among patients receiving CAR T-cell therapy. In particular, we observed significantly higher concentrations of proinflammatory cytokine and neurotoxic kynurenine metabolites in low SES patients, as well as higher baseline LDH associated with higher tumor burden. Earlier CRS onset and increased pain were also seen in low SES patients, with qualitatively higher incidences of CRS, neurotoxicity, and poor sleep. Future work will focus on acquiring a larger sample to further delineate the impact of SES on cancer outcome disparities among CAR T-cell recipients, including but not limited to PROs, neurotoxicity, and survival. Figure 1 Figure 1. Disclosures Shah: Umoja: Consultancy; Incyte: Consultancy; Kite: Consultancy; Epizyme: Consultancy; Miltenyi Biotec: Consultancy, Honoraria, Research Funding; Legend: Consultancy; Lily: Consultancy, Honoraria, Research Funding. Hillard: Formulate Bioscience: Current holder of stock options in a privately-held company; Phytecs, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Patient-reported efficacy and toxicity in CAR T-cell therapy for multiple myeloma via Internet-based platforms.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20024-e20024
Author(s):  
Nathan W. Sweeney ◽  
Eduardo Franco Hernandez ◽  
Nolan Cole ◽  
Scott Ryan Goldsmith ◽  
Zachary Crees ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cell ◽  
Side Effects ◽  
Cell Therapy ◽  
Patient Reported Outcomes ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Patient Reported ◽  
Car T

e20024 Background: Chimeric antigen receptor (CAR) T-cell therapies are in clinical development for multiple myeloma (MM). Patient-reported outcomes (PRO) can provide valuable insights into how patients perceive the relative risks and benefits of these new therapies. This study aimed to evaluate CAR T-cell therapy in relapsed/refractory MM (RRMM) patients. Methods: We utilized HealthTree Cure Hub for Multiple Myeloma to analyze patient-reported data from 17 patients who participated in CAR T-cell clinical trials. In this study, we examined total prior lines of therapy, time to next treatment (TNT), overall survival (OS), patient-reported toxicity and severity, and patient-reported outcomes (myeloma reduction or no myeloma reduction). The Kaplan-Meier model was used to calculate overall survival. The severity of toxicity was assessed using a 1 to 10 scale (1 = minimal and 10 = severe). Results: Our analysis of the 17 patients found a median of 10 lines of therapy prior to CAR T-cell treatment. Ten patients had no new treatments to report at the time of this study, 5 patients reported new treatment with a median TNT of 15.9 months, and for 2 patients we did not have data. The median OS was 24 months (95% CI 21-30 months). The probability that a patient remained alive at 2 years was 0.48 (95% CI: 0.195, 1). Four of the 17 patients died with a median of 22.5 months post-CAR T-cell therapy. Two of these patients died without reporting a change in treatment. There was a total of 36 different side effects reported by patients as a result of the therapy. Table lists the side effects experienced by 2 or more patients and the corresponding average severity. Finally, 76% of patients treated with CAR T-cell therapy reported a reduction in their myeloma, four of these patients had m-protein levels reported and saw an average decrease of 93%. Of the remaining patients, three (18%) reported little to no reduction in their myeloma, and one patient (6%) did not know their response at the time of this analysis. Conclusions: Our investigation of patient-reported results suggests an emerging and viable immunotherapy treatment option for RRMM, with encouraging outcomes and manageable side effects. Future directions include analysis of genetics and treatment options post CAR T-cell therapy. These data highlight the expedited benefit of using PROs via an online platform, like HealthTree Cure Hub, to assess new therapeutics in the research community.[Table: see text]

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