Resource Utilization Early after Chimeric Antigen Receptor (CAR) T Cell Infusion for Hematologic Malignancies
Authors: Shah Gunjan L. , Park Jae H. , Sauter Craig S. , Duck Elaine , Halton Elizabeth , Palomba Maria Lia , Batlevi Connie Lee , Younes Anas , Geyer Mark Blaine , Smith Eric L. , Mailankody Sham , Mead Elena , Santomasso Bianca , Perales Miguel-Angel , Sabbatini Paul , Giralt Sergio , Brentjens Renier J. , Bach Peter 
Published: October 2019

Abstract
Background: Chimeric antigen receptor-modified (CAR) T cells have the potential to provide durable clinical benefit in patients with several relapsed or refractory hematologic malignancies. We aimed to characterize institutional resources utilized (other than T cell collection and CAR T cell manufacturing and infusion) around the time of CAR T cell administration.
Methods: Adult patients treated on selected investigator-initiated clinical trials of CAR T cell therapy at Memorial Sloan Kettering Cancer Center were identified from the institutional database. Utilization data was collected from the start of admission for CAR T cell infusion through the end of the initial admission for infusion or through 30 days following initial CAR T cell infusion, whichever was longer. The data were sorted by disease type and into the categories of encounters, lab work, radiology, medications, and other diagnostic testing. Descriptive statistics were used to analyze the data.
Results: We identified 106 patients on 4 clinical trials receiving inpatient CAR T cell infusions between 6/2007 to 4/2018, with 56 patients (53%) having B-cell acute lymphoblastic leukemia (ALL), 37 (35%) chronic lymphocytic leukemia (CLL) or B-cell non-Hodgkin lymphoma (NHL), and 13 (12%) multiple myeloma (MM). The median age was 53 years (range 22-77), 45 years (range 22-74), 64 years (range 35-77), and 58 years (range 43-68) for the total population, and the ALL, CLL/NHL, and MM groups, respectively, and 65%, 75%, 41%, and 31% were male, respectively.
The median length of stay for the admission during which CAR T cells was given was 23 days (range 4 -133), with ALL patients admitted longer (Figure 1). Intensive care unit (ICU) days were limited with a range of 0-43 days, though 43 (41%) spent at least one day in the ICU. Of note, some protocols required infusion of the CAR T cells to be in the ICU. ICU admissions for ALL patients were than for other histologies longer (median 9 days vs 4 days). Outpatient clinic visits through day 30 post CAR T cell infusion occurred in 57 (53%) patients, with more of these in the CLL/NHL patients (median of 2 visits, range 1-4).
As expected, laboratory and radiology studies accounted for a large portion of resource utilization with a total of 62,953 laboratory panels and 1,190 radiology studies done during the study time frame. Fourteen percent of the labs were complete blood counts, basic or comprehensive metabolic panels, or liver function tests. For the total population, ALL, CLL/NHL, MM, there were a median of 63.5 (range 13-368), 91.5 (21-368), 47 (13-167), and 51 (range 38-113) of these panels done per patient during the time frame, respectively. Blood cultures accounted for 1.3% of the total laboratory tests. Among the radiology studies, 25% were CT scans, 10% MRIs, 7% PET scans, 5% ultrasounds, and 53% x-rays, with differences in patterns of use by disease type (Figure 2). Cardiac testing (echocardiographs & electrocardiograms) was done in 104 (98%, total 634 tests). Electroencephalogram was performed in 18 patients (17%, total 18 tests). There were 173 bone marrow aspirations/biopsies in 88 patients (83%) and 71 lumbar punctures in 38 patients (36%), many of which were potentially done for disease assessment rather than toxicity management.
Finally, 41,331 units of medications were given in this time frame, of which chemotherapy was 328 units (0.8%). The median medication units per patient was 255 (range 35-2091), 423 (range 35-2091), 200 (range 41-1190), and 207 (range 90-666) for the total population, and the ALL, CLL/NHL, and MM patients groups, respectively. Thirty-two doses of tocilizumab were given to 25 patients (24%), with ALL patients receiving 23 of those doses (72%).
Conclusion: While providing potential clinical benefit, CAR T cell therapy utilizes resources across the therapeutic spectrum, and increasing use of this therapeutic modality can create challenges in institutional resource capacity. Identifying these resources will allow for better care delivery and allocation of funds. Further refinement of CAR T cell products and improvements in CAR T cell-related toxicity management may permit safer delivery of this therapy and reduce costs per patient. Additional analysis of resource utilization among patients treated with commercial CAR T cell products, as well as comparison with alternative therapies and cost-effectiveness analysis, is warranted.

Disclosures
Shah: Amgen: Research Funding; Janssen: Research Funding. Park:Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Consultancy; Shire: Consultancy; AstraZeneca: Consultancy; Pfizer: Consultancy; Novartis: Consultancy; Kite Pharma: Consultancy; Juno Therapeutics: Consultancy, Research Funding. Sauter:Juno Therapeutics: Consultancy, Research Funding; Sanofi-Genzyme: Consultancy, Research Funding; Spectrum Pharmaceuticals: Consultancy; Novartis: Consultancy; Precision Biosciences: Consultancy; Kite: Consultancy. Palomba:Pharmacyclics: Consultancy; Celgene: Consultancy. Younes:Genentech: Research Funding; BMS: Honoraria, Research Funding; Pharmacyclics: Research Funding; Abbvie: Honoraria; Merck: Honoraria; Takeda: Honoraria; J&J: Research Funding; Incyte: Honoraria; Janssen: Honoraria, Research Funding; Celgene: Honoraria; Roche: Honoraria, Research Funding; Curis: Research Funding; Astra Zeneca: Research Funding; Novartis: Research Funding; Bayer: Honoraria; Seattle Genetics: Honoraria; Sanofi: Honoraria. Geyer:Dava Oncology: Honoraria. Smith:Celgene: Consultancy, Patents & Royalties: CAR T cell therapies for MM, Research Funding. Mailankody:Physician Education Resource: Honoraria; Janssen: Research Funding; Juno: Research Funding; Takeda: Research Funding. Perales:Incyte: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees and Clinical trial support; Merck: Other: Personal fees; Takeda: Other: Personal fees; Abbvie: Other: Personal fees; Novartis: Other: Personal fees. Brentjens:Juno Therapeutics, a Celgene Company: Consultancy, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding. Bach:Vizient: Other: Personal Fees; Hematology Oncology Pharmacy Assoc: Other: Personal Fees; Excellus Health Plan: Other: Personal Fees; Gilead: Other: Personal Fees; Foundation Medicine: Other: Personal Fees; JMP Securities: Other: Personal Fees; Janssen: Other: Personal Fees; Grail: Other: Personal Fees; American Society for Hospital Pharmacy: Other: Personal Fees; Kaiser Permanente: Research Funding; Third Rock Ventures: Other: Personal Fees; WebMD: Other: Personal Fees; Anthem: Other: Personal Fees; Goldman Sachs: Other: Personal Fees; Novartis: Other: Personal Fees; Defined Health: Other: Personal Fees.