The Impact of Outpatient versus Inpatient Administration of CAR-T Therapies on Clinical, Economic, and Humanistic Outcomes in Patients with Hematological Cancer: A Systematic Literature Review
Abstract
:Simple Summary
Abstract
1. Introduction
2. Methods
2.1. Study Design and Search Process
2.2. Eligibility Criteria
2.3. Data Extraction
2.4. Quality Assessment and Risk of Bias
2.5. Data Analysis
3. Results
3.1. Literature Search Results
3.2. Study Characteristics
3.3. Quality Assessment
3.4. Clinical Outcomes
3.4.1. Safety
3.4.2. Efficacy: Response and Survival Outcomes
3.4.3. Quality of Life
3.5. Economic Outcomes
3.5.1. Direct Costs
3.5.2. Healthcare Resource Utilization
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Study | Country | Trial Name/ID | Study Design | Treatment | Patient Population | Setting (IP/OP/Both) | Sample Size, n | Reason for Different Sample Sizes | List of Outcomes |
---|---|---|---|---|---|---|---|---|---|
Kamdar (2022) [64] | US, Europe, and Japan | TRANSFORM/NCT03575351 | Ph 3 trial | Liso-cel | R/R LBCL (2L+) | Both | 91 | Response, LOS | |
McGarvey (2022) [65] | 90 | Total post-infusion monitoring costs, hospitalizations cost | |||||||
Godwin (2021) [32] | US | OUTREACH/NCT03744676 | Ph 2 trial | Liso-cel | R/R LBCL (3L+) | Both | 34 | Preliminary results 1 | Response, AEs, hospitalizations, LOS |
Godwin (2020) [33] | 34 | Response, AEs, hospitalizations, time to hospitalization, LOS | |||||||
Godwin (2021) [34] | 46 | Preliminary results 2 | Response, AEs | ||||||
Godwin (2021) [35] | 46 | Response, AEs, hospitalizations, time to hospitalization, LOS | |||||||
Godwin (2021) [36] | 71 | Preliminary results 3 | Response, AEs, time to hospitalization, LOS | ||||||
Linhares (2022) [37] | 82 | Updated results | Response, AEs, hospitalizations, time to hospitalization | ||||||
Linhares (2022) [38] | 82 | Response, AEs, hospitalizations, time to hospitalization, QoL | |||||||
Sehgal (2022) [39] | US | PILOT/NCT03483103 | Ph 2 trial | Liso-cel | R/R LBCL (2L+ not intended for HSCT) | Both | 61 | Response, time to response, DOR, PFS, OS, EFS, AEs, hospitalization, ICU admission | |
Sehgal (2019) [40] | R/R aggressive NHL (2L+) | 10 | Subgroup | Response, AEs, HCRU | |||||
McGarvey (2022) [41] | R/R LBCL (2L+ not intended for HSCT) | 61 | Hospitalizations, LOS, monitoring costs | ||||||
Abramson (2020) [42] | US | TRANSCEND NHL 001/NCT02631044 | Ph 1 trial | Liso-cel | R/R LBCL (2L+) | Both | 25 | Preliminary results 1 | Response, PFS, AEs |
Maloney (2017) [43] | R/R B-cell NHL (2L+) | 69 | Preliminary results 2 | AEs | |||||
Palomba (2018) [44] | R/R DLBCL (2L+) | 94 | Updated results | Response, AEs, hospitalizations, time to hospitalization, ICU admission, LOS, OP visits | |||||
Gofshteyn (2018) [45] | US | Pedi CART19/NCT01626495 | Ph 1/2a trial | Tisa-cel | Pediatric and young adults with R/R ALL | OP | 51 | NA | AEs |
Fowler (2021) [66], Fowler (2023) [67] | Multinational | ELARA/NCT03568461 | Ph 2 trial | Tisa-cel | R/R FL (3L+) | Both | 97 | NA | Hospitalizations, LOS, ICU admission, hospitalization costs |
Myers (2020) [46] | US | NCT01626495/NCT02906371/NCT02374333 | Pooled analysis (3 Ph 1/2 trials) | Tisa-cel | Pediatric ALL | 93% patients treated as OPs | 213 | NA | Hospitalizations, LOS, ICU admission, mortality rate, other HCRU |
Shadman (2021) [47] | US | NCT03277729 | Ph 1/2 trial | MB-106 | R/R B-NHL (FL, MCL, DLBCL) and CLL | OP | 25 | Updated results | Response, AEs |
Shadman (2020) [48] | 12 | Preliminary results | |||||||
Shadman (2021) [49] | 12 | ||||||||
Shadman (2022) [50] | R/R FL | 16 | Updated results for a subgroup | ||||||
Turtle (2017) [51] | US | NCT01865617 | Ph 1/2 trial | CD19 CAR-T cells | B-ALL, NHL or CLL | OP | 161 | NA | AEs |
Palomba (2020) [52] | US | - | Cost analysis (pooled trial data) | Liso-cel | R/R LBCL (3L+) | Both | 303 | NA | Standard IP and ICU LOS, costs (diagnostics and procedures, medications, hospitalization/ICU) |
Denlinger (2022) [53] | US | - | Retrospective study | Tisa-cel, axi-cel | BCL | Both | 63 | NA | AEs, LOS, costs and charges, out-of-pocket charges |
Chihara (2022) [54] | US | - | RWE | Any CAR-T | R/R DLBCL | Both | 551 | NA | PFS, OS, hospitalization, ER visits, OP visits (initial and follow-up), costs |
Borogovac (2022) [55], Borogovac (2021) [56] | US | - | Retrospective study | Any CAR-T | DLBCL, FL and ALL, MCL | 91% patients treated as OPs | 23 | NA | Response, AEs |
Shao (2021) [57] | US | - | Retrospective study | Tisa-cel | DLBCL (3L+) | OP | 12 | NA | Response, AEs, hospitalization, LOS |
Yang (2022) [26], Zhao (2021) [58] | US | - | RWE (Medicare claims database) | Tisa-cel, axi-cel | R/R DLBCL | Both | 430 | NA | ICU admission, LOS, costs |
Farooqui (2022) [59] | US | - | Retrospective study | Axi-cel | NHL | OP | 83 | NA | AEs, ICU admission |
Nasta (2022) [60] | US | - | Retrospective study | Tisa-cel | Lymphoma (3L+) | OP | 72 | NA | Response, OS, PFS, AEs |
Maziarz (2021) [61] Maziarz (2022) [62] | US | - | Retrospective study | Tisa-cel, axi-cel | R/R DLBCL | Both | 119 | NA | Hospitalizations, ICU admissions, LOS, OP visits, costs |
Hospitalizations, ICU, LOS, OP visits (initial and follow-up), costs | |||||||||
Wright (2020) [68] | NR | - | Retrospective study | Axi-cel/tisa-cel | R/R NHL | Both | 31 | NA | Hospitalizations, LOS |
Kirby (2022) [63] | US | - | Retrospective study | Axi-cel, tisa-cel, brexu-cel, liso-cel | R/R BCL | OP | 20 | NA | PFS, OS, AEs, hospitalizations |
Study | Study/Trial Name/Trial ID | Treatment | Setting (IP/OP) | n | Age, Median (Years) | Age ≥ 65, (%) | Male (%) | ECOG PS (%) | Number of Prior Lines | Prior Transplant Therapy, (%) | Refractory Patients, (%) |
---|---|---|---|---|---|---|---|---|---|---|---|
Godwin (2021) [36] | OUTREACH/NCT03744676 | Liso-cel | OP | 54 | 64.5 | 50.0 | 70.0 | 0: 33.0 1: 67.0 | 2.0 (2.0–4.0) * | 20.0 | 89.0 |
IP | 23 | 68.0 | 61.0 | 61.0 | 0: 26.0 1: 74.0 | 2.0 (1.0–6.0) * | 9.0 | 96.0 | |||
Fowler (2021) [66], Fowler (2023) [67] | ELARA/NCT03568461 | Tisa-cel | OP | 17 | NR | 23.5 | 76.5 | ≥1: 23.5 | ≥5: 41.2% | NR | 41.2 |
IP | 80 | NR | 25.0 | 63.8 | ≥1: 47.5 | ≥5: 25.0% | NR | 26.3 | |||
Gofshteyn (2018) [45] | Pedi CART19—NCT01626495 | Liso-cel | OP | 51 | 11.5 | NR | 49.0 | NR | NR | NR | NR |
Shadman (2022) [50] | NCT03277729 | MB-106 (CD20 CART-T) | OP | 16 | 61.5 | NR | NR | NR | NR | NR | NR |
Myers (2020) [46] | NCT01626495/NCT02906371/NCT02374333 | Tisa-cel | OP | 213 | 12.4 | NR | 60.0 | NR | NR | NR | NR |
Shao (2021) [57] | NR | Tisa-cel | OP | 12 | 69.5 | 83.0 | 66.7 | NR | 2: 75.0% 3: 25.0% | 16.7 | NR |
Zhao (2021) [58], Yang (2022) [26] | NR | Tisa-cel, axi-cel | OP | 50 | Mean: 68.4 | NR | 70.0 | NR | NR | NR | NR |
IP | 380 | Mean: 70.8 | NR | 62.4 | NR | NR | NR | NR | |||
Farooqui (2022) [59] | NR | Axi-cel | OP | 83 | Mean: 55.2 | NR | 65.1 | NR | NR | NR | NR |
Nasta (2022) [60] | NR | Tisa-cel | OP | 72 | 65.7 | NR | 58.3 | 0: 31.9 1: 62.5 2: 4.2 NR: 1.4 | NR | 18.1 | NR |
Kirby (2022) [63] | NR | Tisa-cel, axi-cel, liso-cel, brexu-cel | OP | 20 | 69.5 | NR | 60.0 | ≥2: 25.0 | NR | NR | NR |
First Author, Year | Trial Name/ID | Study Design | Patient Population | Treatment | Site of Care | Follow-Up | n | CRS-Related Toxicity (%) | Neurologic Toxicity (%) | Other AEs (%) |
---|---|---|---|---|---|---|---|---|---|---|
Linhares (2022) [37] | OUTREACH/NCT03744676 | Ph 2 trial | R/R LBCL (3L+) | Liso-cel | Outpatient vs. inpatient | NA | 54 vs. 25 | Any grade: 37.0 vs. 44.0 | Any grade: 30.0 vs. 32.0 Grade 3–4: 13.0 vs. 4.0 | Infection: Any grade, 33 vs. 32; Grade 3–4, 13.0 vs. 4.0. Prolonged cytopenia at Day 29 visit: Any grade, 33.0 vs. 32.0. Hypogammaglobulinemia: Any grade, 11.0 vs. 4.0 |
Fowler (2023) [67] | ELARA/NCT03568461 | Ph 2 trial | R/R FL (3L+) | Tisa-cel | Outpatient vs. inpatient | Median: 20 months | 17 vs. 80 | Any grade: 52.9 vs. 47.5 | Any grade: 5.9 vs. 11.3 Grade 3–4: 0.0 vs. 1.3 | At least 1 AE: Any grade, 82.4 vs. 92.5; Grade 3–4, 47.1 vs. 75. Hematological disorders, including cytopenias: Any grade, 64.7 vs. 77.5; Grade 3–4, 47.1 vs. 73.8. Infections: Any grade, 17.6 vs. 21.3; Grade 3–4, 0.0 vs. 7.5. Prolonged depletion of normal B cells or agammaglobulinemia: Any grade, 11.8 vs. 10.0. Tumor lysis syndrome: Any grade: 0.0 vs. 1.3; Grade 3–4, 0.0 vs. 1.3 |
Sehgal (2022) [39] | PILOT/NCT03483103 | Ph 2 trial | R/R LBCL (2L+ not intended for HSCT) | Liso-cel | Outpatient vs. inpatient | Median: 12.3 months | 20 vs. 41 | Any grade: 15.0 vs. 48.0 | Any grade: 10.0 vs. 41.0 | NA |
Abramson (2020) [42] | TRANSCEND NHL 001/NCT02631044 | Ph 3 trial | R/R LBCL (2L+) | Liso-cel | Outpatient vs. inpatient | Median: 18.8 months | 25 vs. 244 | Any grade: 40.0 vs. 42.0 Grade 3–4: 4.0 vs. 2.0 | Any grade: 44.0 vs. 28.0 Grade 3–4: 8.0 vs. 10.0 | NA |
Denlinger (2022) [53] * | NA | Retrospective study | BCL | Tisa-cel vs. axi-cel | Outpatient vs. inpatient | NA | 18 vs. 45 | Any grade: 44.0 vs. 96.0 | Any grade: 22.0 vs. 73.0 | NA |
First Author, Year | Trial Name/ID | Study Design | Patient Population | Treatment | Follow-Up | Sample Size, n | CRS-Related Toxicity (%) | Neurologic Toxicity (%) | Other AE (%) |
---|---|---|---|---|---|---|---|---|---|
Gofshteyn (2018) [45] | Pedi CART19/NCT01626495 | Ph 1/2a trial | Pediatric and young adult patients with R/R ALL | Tisa-cel | NA | 51 | Any grade: 92.0 | Any neurotoxicity: 45.0 Common neurotoxicity: 41.0 | NA |
Turtle (2017) [51] | NCT01865617 | Ph 1/2 trial | B-ALL, NHL or CLL | Anti-CD19 CAR-T cell therapy | NA | 133 | Any grade: 71.0 Grade 1–2: 60.0 Grade 3: 4.0 Grade ≥ 4: 8.0 | Any grade: 40.0 Grade 1–2: 19.0 Grade 3: 16.0 Grade ≥ 4: 5.0 | NA |
Shadman (2021) [49] | NCT03277729 | Ph 1/2 trial | R/R B-NHL and CLL (FL, MCL, CLL, DLBCL) Entire cohort | CD20 CAR-T cells | NA | 12 | Grade 1: 16.0 Grade 2: 8.0 | NA | NA |
Shadman (2021) [47] | NCT03277729 | Ph 1/2 trial | FL | CD20 Targeted CAR T-cell therapy (MB-106) | Maximum 13.0 months post-infusion | 18 | Grade 1: 22.0 Grade 2: 5.5 Grade 3: 0.0 Grade 4: 0.0 | Grade 1: 0.0 Grade 2: 0.0 Grade 3: 0.0 Grade 4: 0.0 | NA |
CLL, MCL, DLBCL, WM | 7 | Grade 1: 28.0 Grade 2: 28.0 Grade 3: 0.0 Grade 4: 0.0 | Grade 1: 14.0 Grade 2: 14.0 Grade 3: 0.0 Grade 4: 0.0 | NA | |||||
FL, CLL, MCL, DLBCL, WM | 25 | Grade 1: 24.0 Grade 2: 12.0 Grade 3: 0.0 Grade 4: 0.0 | Grade 1: 4.0 Grade 2: 4.0 Grade 3: 0.0 Grade 4: 0.0 | NA | |||||
Shadman (2020) [48] | NCT03277729 | Ph 1/2 trial | R/R B-cell NHL | CD20 CAR-T | NA | 11 | NA | NA | Grade ≥ 3 AEs Anemia: 36.0 Lymphopenia: 27.0 Neutropenia: 18.0 Hypertension: 9.0 Hypotension: 9.0 Thromboembolic event: 9.0 Neutropenia: 9.0 Elevated alkaline phosphatase: 9.0 Pneumonia: 9.0 Bacteremia: 9.0 Hyperglycemia: 9.0 Pleural effusion: 9.0 Generalized pain: 9.0 |
Shao (2021) [57] | NA | Retrospective study | DLBCL | Tisa-cel | Median: 29.1 weeks, (range: 2.6–60.0) | 12 | Any grade: 50.0 Grade 3–4: 8.3 | Any grade: 8.3 Grade 3–4: 0.0 | Any grade AEs Anemia: 75.0 Thrombocytopenia: 66.7 Neutropenia: 66.7 Grade 3–4 AEs Anemia: 33.3 Thrombocytopenia: 37.5 Neutropenia: 66.7 |
Borogovac (2022) [55] | NA | Retrospective study | DLBCL, ALL, MCL | Axi-cel | NA | 13 | Any grade: 69.0 Grade 3–4: 8.0 | Any grade: 31.0 Grade 3–4: 0.0 | NA |
Tisa-cel | NA | 6 | Any grade: 50.0 Grade 3–4: 17.0 | Any grade: 17.0 Grade 3–4: 17.0 | NA | ||||
Brexu-cel | NA | 1 | Any grade: 0.0 Grade 3–4: 0.0 | Any grade: 100 Grade 3–4: 0.0 | NA | ||||
Liso-cel | NA | 1 | Any grade: 0.0 Grade 3–4: 0.0 | Any grade: 0.0 Grade 3–4: 0.0 | NA | ||||
Farooqui (2022) [59] | NA | Retrospective study | Refractory NHL, patients without acute kidney injury | Axi-cel | NA | 69 | Incidence: 85.5 Grade None: 14.5 Grade 1: 49.3 Grade 2: 34.8 Grade 3: 0.0 Grade 4: 1.4 | Incidence: 52.2 Grade None: 47.8 Grade 1: 21.7 Grade 2: 18.8 Grade 3: 7.2 Grade 4: 4.3 | NA |
Refractory NHL, patients with acute kidney injury | Axi-cel | NA | 14 | Incidence: 85.7 Grade None: 14.3 Grade 1: 35.7 Grade 2: 42.9 Grade 3: 0.0 Grade 4: 7.1 | Incidence: 57.1 Grade None: 42.9 Grade 1: 7.1 Grade 2: 21.4 Grade 3: 21.4 Grade 4: 7.1 | NA | |||
Nasta (2022) [60] | NA | Retrospective study | Lymphoma (3L+) | Tisa-cel | Median: 39.5 weeks (range: 3.0–127.3) | 72 | None: 59.7 Grade 1: 22.2 Grade 2: 18.1 | None: 94.4 Grade 1: 2.8 Grade 3–4: 2.8 | NA |
Kirby (2022) [63] | NA | Retrospective study | R/R BCL | Tisa-cel, axi-cel, liso-cel, and brexu-cel | NA | 20 | Any grade: 55.0 Grade ≥ 3: 5.0 | All grades: 45.0 Grade ≥ 3: 25.0 | Late infection events: 29.0, Hypogammaglobulinemia (IgG < 400 mg/dL or IVIg) Pre-lymphodepletion: 31.0 Late hypogammaglobulinemia: 83.0 |
Axi-cel | NA | 3 | Grade ≥ 3: 33.0 | Grade ≥ 3: 67.0 | NA | ||||
Liso-cel | NA | 14 | NA | Grade ≥ 3: 7.0 | NA | ||||
Brexu-cel | NA | 1 | NA | Grade ≥ 3: 100 | NA |
Study | Trial Name/ID | Study Design | Patient Population | Treatment | Follow-Up | Outpatients | Inpatients | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
n | ORR % (95% CI) | CR % (95% CI) | PR % (95% CI) | Other Details | n | ORR % (95% CI) | CR % (95% CI) | PR % (95% CI) | Other Details | ||||||
Linhares (2022) [37], Godwin (2021) [36] | OUTREACH | Ph 2 trial | R/R LBCL (3L+) | Liso-cel | NR | 57 | 82.4 (70.0–91.0) | 58.0 | 25.0 | SD: 5.0% Median DOR: 15.1 (3.9–NR) | 25 | 76.0 (55.0–91.0) | 44.0 | 32.0 | SD: 12.0; median DOR: 14.8 (2.0–NR) |
Sehgal (2022) [39] | PILOT | Ph 2 trial | R/R LBCL (2L+) | Liso-cel | Median: 104.3 weeks | 20 | 80.0 (56.3–94.3) | 50.0 (27.2–72.8) | 30.0 | Median DOR: 8.2 (2.1–NR) | 41 | 80.0 | 56.0 | 24.0 | IP/OP (n = 61); SD: 5.0%; median DOR: 12.1 (6.2–NR) |
Abramson (2020) [42] | TRANSCEND NHL 001 | Ph 2 trial | R/R LBCL (2L+) | Liso-cel | NR | 25 | 80.0 (59.3–93.2) | 56.0 (34.9–75.6) | 24.0 | Median DOR: NR (2.4–NR) | 231 | 72.0 | 53.0 | 19.0 | IP/OP (n = 256): ORR: 73.0%, CR: 53.0% |
Shadman (2021) [47] | NCT03277729 | Ph 1/2 trial | R/R FL | CAR-T cells | 13.0 months post-infusion | 18 | 94.0 | 78.0 | 17.0 | NR | NA | NA | NA | NA | NA |
R/R MCL, CLL, DLBCL, WM/LPL | 7 | 100.0 | 57.0 | 43.0 | NR | NA | NA | NA | NA | NA | |||||
Borogovac (2022) [57] | - | Obs. study | DLBCL and ALL | Axi-cel | 1.0 month | 13 | 77.0 | 69.0 | 8.0 | PR or SD: 8.0% | NR | NR | NR | NR | NR |
Tisa-cel, brexu-cel, liso-cel | 8 | 87.5 | 75.0 | 12.5 | PR or SD: 13.0% | NR | NR | NR | NR | NR | |||||
Nasta (2022) [60] | - | Obs. Study | Lymphoma | Tisa-cel | 39.5 weeks | 72 | 43.0 | 34.7 | 8.3 | SD: 5.6% | NR | NR | NR | NR | NR |
Shao (2021) [57] | - | Obs. study | DLBCL | Tisa-cel | 29.1 weeks | 12 | 58.0 | 25.0 | 33.0 | SD: 8.3% | NR | NR | NR | NR | NR |
Shadman (2021) [47] | NCT03277729 | Ph 1/2, CT | FL | CAR-T cells | 13.0 months post-infusion | 18 | 94.0 | 78.0 | 17.0 | NR | NR | NR | NR | NR | NR |
DLBCL | 2 | 100 | 50.0 | 50.0 | NR | NR | NR | NR | NR | NR | |||||
WM/LPL | 2 | 100 | 100 | 0 | NR | NR | NR | NR | NR | NR | |||||
CLL | 1 | 100 | 100 | 0 | NR | NR | NR | NR | NR | NR | |||||
MCL | 2 | 100 | NR | 100 | NR | NR | NR | NR | NR | NR | |||||
Borogovac (2022) [57] | - | Obs. Study | DLBCL and ALL | Axi-cel | 1.0 month | 13 | 77.0 | 69.0 | 8.0 | PR or SD: 8.0% | NR | NR | NR | NR | NR |
Tisa-cel | 6 | 100 | 83.0 | 17.0 | PR or SD: 17.0% | NR | NR | NR | NR | NR | |||||
Brexu-cel | 1 | 100 | 100 | 0 | PR or SD: 0.0% | NR | NR | NR | NR | NR | |||||
Liso-cel | 1 | 0 | 0 | 0 | PR or SD: 0.0% | NR | NR | NR | NR | NR | |||||
Nasta (2022) [60] | - | Obs. Study | Lymphoma | Tisa-cel No Bridging | 39.5 weeks | 17 | 53.0 | 29.4 | 23.5 | SD: 5.9% | NR | NR | NR | NR | NR |
Tisa-cel Bridging | 55 | 40.0 | 36.4 | 3.6 | SD: 5.5% | NR | NR | NR | NR | NR |
Study | Trial Name/ID | Study Design | Patient Population | Treatment | Follow-Up | Outpatient | Inpatient | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
n | Median PFS in Months (95% CI) | PFS Rate (95% CI) | Other Data | n | Median PFS in Months (95% CI) | PFS Rate (95% CI) | Other Data | ||||||
Linhares (2022) [37] | OUTREACH | Ph 2 trial | R/R LBCL (3L+) | Liso-cel | 57 | 6.1 (2.9-NR) | 12-mo: 41.0% | - | 25 | 4.3 (2.8-NR) | 12-mo: 39.0% | ||
Fowler (2023) [67] | ELARA | Ph 2 trial | R/R FL (3L+) | Tisa-cel | 20.0 months | 17 | NA | 12-mo: 60% 18-mo: 57.0% | - | 80 | NA | 12-mo: 70.0% 18-mo: 62.5 (34.9–81.1) | - |
Sehgal (2022) [39] | PILOT | Ph 2 trial | R/R LBCL (2L+) | Liso-cel | 12.3 (IQR, 6.1–18.0) | 20 | 7.2 (2.4- 13.0) | NR | Median EFS: 7.1 months (2.4–13.0) | NA | NA | NA | Overall patients (n = 61) Median PFS: 9.0 months (4.2–NR) |
Abramson (2020) [42] | TRANSCEND NHL 001 | Ph 1 trial | R/R LBCL (2L+) | Liso-cel | 18.8 months | 25 | NR (3.0–NR) | NR | - | NA | NA | NA | Overall patients (n = 256) Median PFS: 6.8 months (3.3–14.1) 6-mo PFS: 51.4% (45.0–58.0) 12-mo PFS: 44.1% (37.3–50.7) |
Kirby (2022) [63] | Kirby 2022 | Retr. study | R/R BCL | Liso-cel, axi-cel, tisa-cel, brexu-cel | >3.3 months | 20 | NR | 6-mo: 65.0% 12-mo: 60.0% | - | - | - | - | - |
Study | Trial Name/ID | Study Design | Patient Population | Treatment | Follow-Up | Outpatient | Inpatient | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
n | Median OS in Months (95% CI) | OS Rate (95% CI) | Other Data | n | Median OS in Months (95% CI) | OS Rate (95% CI) | Other Data | ||||||
Linhares (2022) [37] | OUTREACH | Ph 2 trial | R/R LBCL (3L+) | Liso-cel | - | 57 | NR (NR-NR) | 12-mo: 60.0% | - | 25 | 22.2 (8.0-NR) | 12-mo: 60.0% | - |
Sehgal (2022) [39] | PILOT | Ph 2 trial | R/R LBCL (2L+) | Liso-cel | 12.3 (IQR, 6.1–18.0) | 20 | NR (10.5–NR) | NA | - | NA | NA | NA | Overall patients (n = 61): 17.6 months Median (months) (95% CI): Not reached (19.3-not reached) |
Nasta (2022) [60] | Nasta 2022 | Retr. study | Lymphoma | tisa-cel | 9.1 | 72 | 26.5 (19.0–NR) | NA | - | - | - | - | - |
Kirby (2022) [63] | Kirby 2022 | Retr. study | R/R BCL | Liso-cel, axi-cel, tisa-cel, brexu-cel | >3.3 months | 20 | NA | 6-mo: 85.0% 12-mo: 75.0% | - | - | - | - | - |
Shadman (2021) [47] | NCT03277729 | Ph 1/2 trial | R/R B-NHL and CLL | MB-106 (CD20 CAR-T) | 8.9 | 25 | NA | 1.0 | 1 death over FU | - | - | - | - |
R/R FL | MB-106 (CD20 CAR-T) | 9.3 | 18 | NA | 0.9 | 1 death over FU | - | - | - | - |
Study | Instruments | Domains | Outpatient (n = 54), LS Mean Change from Baseline (95% CI) | Inpatient (n = 28), LS Mean Change from Baseline (95% CI) | p Value |
---|---|---|---|---|---|
Linhares (2022) [38] (OUTREACH) | EORTC QLQ-C30 | GH/QoL | 7.80 (3.99–11.61) | 10.39 (5.37–15.42) | 0.415 |
Physical functioning | 0.38 (−1.11 to 4.08) | 3.50 (−1.33 to 8.34) | 0.312 | ||
Role functioning | 5.17 (0.27–10.01) | 4.8 (−1.63 to 11.21) | 0.927 | ||
Cognitive functioning | 0.71 (−1.08 to 4.51) | 1.83 (−3.19 to 6.84) | 0.716 | ||
Fatigue | −6.28 (−10.73 to −1.82) | −11.18 (−16.99 to −5.36) | 0.188 | ||
Pain | −13.46 (−17.50 to −9.41) | −13.25 (−18.51 to −8.00) | 0.951 | ||
EQ-5D-5L | HUI | 0.02 (−0.02 to 0.06) | 0.04 (−0.01 to 0.10) | 0.51 | |
VAS | 7.48 (4.10–10.86) | 10.34 (5.76–14.91) | 0.31 |
First Author, Year | Trial Name/ID | Country for Cost Analysis | Study Design | Patient Population | Treatment | Cost Components | Follow-Up | Site of Care: Outpatient | Site of care: Inpatient | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
n | Total Costs | Hosp. Costs | Other Costs | n | Total Costs | Hosp. Costs | Other Costs | ||||||||
Palomba (2020) [52] | TRANSCEND NHL 001 and OUTREACH | US | Pooled analysis | R/R LBCL (3L+) | Liso-cel | IP and ICU LOS, diagnostics, procedures, medications | 6.0 months | 47 | 6-month post-infusion cost: USD 36,702 First month: USD 19,837 | NA | NA | 256 | 6-month post-infusion cost: USD 89,535 First month: USD 50,369 | NA | NA |
Denlinger (2022) [53] * | NA | US | Retrospective study | BCL | Tisa-cel; axi-cel | NA | Median: Axi-cel: 31.4 months Tisa-cel: 23.8 months | 18 | Tisa-cel (outpatient *): Median (range): USD 64,834 (USD 4007–USD 429,380) | NA | NA | 45 | Axi-cel (inpatient *): Median (range): USD 176,535 (USD 30,977–USD 1187,965) | NA | NA |
McGarvey (2022) [41] | PILOT/NCT03483103 | US | Ph 2 trial | R/R LBCL (2L+) not intended for HSCT | Liso-cel | IP and ICU LOS, diagnostics, procedures, medications | NA | 20 | 6-month post-infusion monitoring cost: USD 16,172 First month: USD 13,261 | USD 9455 | NA | 41 | 6-month post-infusion monitoring cost: USD 61,772 First month: USD 46,947 | USD 49,495 | NA |
McGarvey (2022) [65] | TRANSFORM/NCT03575351 | US | Ph 3 trial | R/R LBCL (2L+) | Liso-cel | IP and ICU LOS, diagnostics, procedures, medications | NA | 19 | 6-month post-infusion monitoring cost: USD 38,314 First month: USD 18,774 | USD 20,867 | NA | 71 | 6-month post-infusion monitoring cost: USD 96,297 First month: USD 49,111 | USD 69,153 | NA |
Fowler (2023) [67] | ELARA/NCT03568461 | US | Ph 2 trial | R/R FL (3L+) | Tisa-cel | IP and ICU LOS | Median: 20.0 months | 17 | NA | USD 7477 | NA | 80 | NA | USD 40,054 | NA |
Maziarz (2022) [62] | NA | US | Retrospective study | R/R DLBCL | Tisa-cel, axi-cel | IP and OP | Mean: 5.0 months | Tisa-cel: 8 | For FU period: Tisa-cel: USD 13,389 For infusion encounter: Tisa-cel: USD 4741 | Tisa-cel: USD 4753 | OP costs: Tisa-cel: USD 8636 | Tisa-cel: 25 Axi-cel: 86 | For FU period: Axi-cel: USD 46,575 Tisa-cel: USD 33,701 Infusion encounter: Axi-cel: USD 51,378 Tisa-cel: USD 34,908 | For FU period: Axi-cel: USD 44,561 Tisa-cel: USD 29,953 | For FU period: OP costs: Axi-cel: USD 2014 Tisa-cel: USD 3748 |
Yang (2022) [26] ** | NA | US | RWE | R/R DLBCL | Tisa-cel, axi-cel | IP, ER, OP, other medical services, medications | CAR-T IP: 6.6 months, CAR-T OP: 6.0 months | 50 | Total Medicare reimbursement amounts for months 1, 2, 3, 4, 5, 6, and 7: USD 371,839, USD 9120, USD 4927, USD 8300, USD 8102, USD 6724, and USD 10,883, respectively | NA | NA | 380 | Total Medicare reimbursement amounts for months 1, 2, 3, 4, 5, 6, and 7: USD 348,364, USD 9756, USD 7318, USD 8259, USD 7052, USD 5748, and USD 6741, respectively | NA | NA |
Study Details | Treatment | Outpatient Cohort | Inpatient Cohort | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
n | OP Visits | Hospitalization Rate | Time to Hospitalization | Reasons for Hospitalization | LOS | ICU Admissions | n | OP Visits | Hospitalization Rate | Time to Hospitalization | LOS | ICU Admissions | ||
Chihara (2022) [54] | Any CAR-T therapy | 95 | NA | Follow-up hospitalization: 41.8% | NA | NA | NA | NA | 456 | NA | Within 90 days: rehospitalization: 28.7% | NA | 21.4 days | NA |
Wright (2020) [68] | Tisa-cel, axi-cel | 12 | NA | Unplanned hospitalization: 33.0% | NA | NA | NA | NA | 19 | NA | Unplanned hospitalization: 26.0% | NA | NA | NA |
Palomba (2020) [52] | Liso-cel | 47 | 100% | 62.0% | NA | NA | Total: 7.8 (SD, 13.1) days ICU: 0.6 (SD, 2.8) days | 6.0% | 256 | 93.0% | ~100% | NA | Total: 20.1 (SD, 15.1) days ICU: 1.1 (SD, 5.5) days | 7.0% |
Sehgal (2022) [39] | Liso-cel | 20 | NA | Total: 45.0% Within 72 h: 10.0% | Median: 6.0 (IQR, 5.0–10.0) days | AEs: 78.0% Other: 22.0% | Initial hospitalization: Mean: 2.5 (SD, 3.2) days Median: 5.0 (IQR, 4.0–7.0) days ICU: Mean: 3.0 days Median: 3.0 (IQR, 3.0–3.0) days | 5.0% | 41 | NA | Total: 100% | NA | Initial hospitalization: Mean: 11.9 (SD, 5.1) days Median: 12.0 (8.0–15.0) days ICU: Mean: 2.5 (SD, 0.7) days Median: 2.5 (IQR, 2.0–3.0) days | 20.0% |
Yang (2022) [26] | Tisa-cel, axi-cel | 50 | NA | Within the 1st month: 52.0% | NA | NA | LOS for months 1, 2, 3, 4, 5, 6, and 7: 5.2, 1.6, 1.2, 1.3, 1.4, 0.7, and 0.9 days, respectively ICU LOS: for months 1, 2, 3, 4, 5, 6, and 7: 0.6, 0.1, 0.1, 0.3, 0, 0, and 0.1 days, respectively | NA | 380 | NA | Within the 1st month: 100% (by definition) | NA | LOS for months 1, 2, 3, 4, 5, 6 and 7: 20.4, 4.6, 2.4, 2.0, 1.4, 1.1 and 1.0 days, respectively ICU LOS: for months 1, 2, 3, 4, 5, 6 and 7: 2.4, 0.1, 0.1, 0.1, 0.1, 0.1, and 0.1 days, respectively | NA |
Fowler (2023) [67] | Tisa-cel | 17 | NA | 59.0% | 5.8 (SD, 7.1) days | CRS: 53.0% | Total: Mean: 4.3 (SD, 1.4) days Median: 4.5 days ICU: 0.0 days | 0.0% | 80 | NA | 100% | NA | Total: Mean: 13.8 (SD, 8.5) days Median: 12.5 days ICU: Median: 4.0 days | 9.0% |
Linhares (2022) [37] | Liso-cel | 54 | NA | Overall hospitalization: 76.0% Within 4 days: 31.0% | Median: 5.0 days (2.0–310.0 days) | AEs: 83.0% Other: 17.0% | Initial hospital stay: Median: 6.0 (1.0–28.0) days ICU: Median: 3.5 (2.0–5.0) days | 4.0% | 25 | NA | 100% | NA | Initial hospital stay: Median initial stay: 13.0 days (1.0–31.0) | NA |
McGarvey (2022) [65] | Liso-cel | 19 | NA | NA | NA | NA | Median: 9.0 (range, 4.0–33.0) days | NA | 71 | NA | NA | NA | Median: 15.0 (range, 1.0–164.0) days | NA |
Denlinger (2022) [53] | Tisa-cel, axi-cel | Tisa-cel: 18 | NA | NA | NA | NA | Tisa-cel: 9.0 days | NA | Axi-cel: 45 | NA | NA | NA | Axi-cel: 14.0 days | NA |
Maziarz (2022) [61] | Tisa-cel, axi-cel | Tisa-cel: 8 | 100% | 63.0% | NA | NA | Mean: 1.7 days ICU: 0.4 days | 38.0% | Axi-cel: 86 Tisa-cel: 25 | Axi-cel: 52.0% Tisa-cel: 76.0% | NA | NA | Axi-cel: 6.9 days Tisa-cel: 4.6 days | Axi-cel: 30.0% Tisa-cel: 16.0% |
Myers (2020) [46] | Tisa-cel | 198 * | NA | Within 30 days: 70.0% | NA | NA | Median: 7.0 (IQR, 4.0–13.0) days | 23.0% | 15 * | NA | NA | NA | NA | NA |
Kamdar (2022) [64] | Liso-cel | 19 | NA | 68.0% | Median: 9.0 (IQR, 4.0–19.0) days | CRS: 38.0% Other AEs: 38.0% PD: 8.0% Other: 15.0% | Median: 9.0 (IQR, 5.0–9.0) days | 0.0% | NA | NA | NA | NA | NA | NA |
Kirby (2022) [63] | Tisa-cel, axi-cel, liso-cel, brexu-cel | 20 | NA | Within 1st month of therapy: Overall: 50.0% Axi-cel: 67.0% Liso-cel: 36.0% Tisa-cel: 100% Brexu-cel: 100% | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
Nasta (2022) [60] | Tisa-cel | 68 | NA | Within 72 h: 19.4% Within 30 days: 36.1% | NA | CRS: 85% Infection: 8% Colitis: 4% Catatonia: 4% | Median: 5.0 days | NA | 4 | NA | NA | NA | NA | NA |
Shao (2021) [57] | Tisa-cel | 12 | NA | Within 30 days: 50.0% | Median: 4.0 days (2.0–12.0 days) | CRS: 83.0% Colitis: 17.0% | Median: 5.5 days (2.0–9.0) days | NA | NA | NA | NA | NA | NA | NA |
Borogovac (2022) [55] | Axi-cel, tisa-cel, brexu-cel, liso-cel | 21 | NA | Post therapy: Within 72 h/within 1st month: Overall: 24.0%/71.0% Axi-cel: 23.0%/76.0% Liso-cel: 0.0%/0.0% Tisa-cel: 33.0%/67.0% Brexu-cel: 0.0%/100% | Median: 4.0 (1.0–28.0) days | Fever: 87.0% CNS toxicity: 13.0% | Median: 8.0 days (1.0–30.0) | NA | 2 | NA | NA | NA | NA | NA |
Farooqui (2022) [59] | Axi-cel | With AKI: 14 Without AKI: 69 | NA | NA | NA | NA | NA | With AKI: 42.9% Without AKI: 29.0% | NA | NA | NA | NA | NA | NA |
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Hansen, D.K.; Liu, Y.-H.; Ranjan, S.; Bhandari, H.; Potluri, R.; McFarland, L.; De Braganca, K.C.; Huo, S. The Impact of Outpatient versus Inpatient Administration of CAR-T Therapies on Clinical, Economic, and Humanistic Outcomes in Patients with Hematological Cancer: A Systematic Literature Review. Cancers 2023, 15, 5746. https://doi.org/10.3390/cancers15245746
Hansen DK, Liu Y-H, Ranjan S, Bhandari H, Potluri R, McFarland L, De Braganca KC, Huo S. The Impact of Outpatient versus Inpatient Administration of CAR-T Therapies on Clinical, Economic, and Humanistic Outcomes in Patients with Hematological Cancer: A Systematic Literature Review. Cancers. 2023; 15(24):5746. https://doi.org/10.3390/cancers15245746
Chicago/Turabian StyleHansen, Doris K., Yi-Hsuan Liu, Sandip Ranjan, Hitesh Bhandari, Ravi Potluri, Lindsay McFarland, Kevin C. De Braganca, and Stephen Huo. 2023. "The Impact of Outpatient versus Inpatient Administration of CAR-T Therapies on Clinical, Economic, and Humanistic Outcomes in Patients with Hematological Cancer: A Systematic Literature Review" Cancers 15, no. 24: 5746. https://doi.org/10.3390/cancers15245746