Fluctuation of Physical Function During Chimeric Antigen Receptor T-cell Therapy During Rehabilitation Intervention: Real-world Data and Risk Factor Analyses

Overview

Journal EJHaem

Specialty Hematology

Date 2024 Dec 18

PMID 39691237

Authors

Ryota Hamada

Yasuyuki Arai

Toshio Kitawaki

Naokazu Nakamura

Masanobu Murao

Michiko Matsushita

Junsuke Miyasaka

Tsugumi Asano

Tomoyasu Jo

Momoko Nishikori

Junya Kanda

Chisaki Mizumoto

Kouhei Yamashita

Ryosuke Ikeguchi

Akifumi Takaori-Kondo

Affiliations

Soon will be listed here.

Abstract

Introduction: Patients undergoing chimeric antigen receptor (CAR) T-cell therapy face prolonged treatment timelines and are prone to cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) after infusion. Disabilities in physical function and the importance of rehabilitation during CAR-T-cell therapy to maintain physical function have been poorly documented.

Method: We performed a retrospective cohort study to assess changes in exercise tolerance via differences in a 6-min-walking distance (Δ6MWD) and factors influencing it.

Results: A total of 77 patients who underwent rehabilitation during CAR-T-cell therapy were enrolled, and their 6MWD was 450 m (median, range 180-705 m) before and 450.5 m (107.0-735.0 m) 30 days after CAR-T treatment. No significant alteration in Δ6MWD was observed overall (11.0 m, 95% confidence interval, -56.1 to 88.2 m). Multiple regression analyses indicated that age (over vs. under 65 years) revealed no notable differences in Δ6MWD (20 vs. 10 m), while ΔHb ( = 0.24, = 0.03), moderate/severe CRS (grade 1 with continuous fever or grade ≥2; = -0.25, = 0.03), and ICANS (any grade; = -0.22, = 0.04) were significantly associated with lower Δ6MWD.

Conclusion: This real-world study indicated that CAR-T-cell therapy is less likely to reduce physical function even in older patients if rehabilitation is properly performed, whereas CRS and ICANS can be risk factors to deprive exercise tolerance.

References

Berdeja J, Madduri D, Usmani S, Jakubowiak A, Agha M, Cohen A . Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. Lancet. 2021; 398(10297):314-324. DOI: 10.1016/S0140-6736(21)00933-8. View

Dean E, Mhaskar R, Lu H, Mousa M, Krivenko G, Lazaryan A . High metabolic tumor volume is associated with decreased efficacy of axicabtagene ciloleucel in large B-cell lymphoma. Blood Adv. 2020; 4(14):3268-3276. PMC: 7391155. DOI: 10.1182/bloodadvances.2020001900. View

Fang J, Zhou F . BCMA-targeting chimeric antigen receptor T cell therapy for relapsed and/or refractory multiple myeloma. Ann Hematol. 2023; 103(4):1069-1083. DOI: 10.1007/s00277-023-05444-7. View

Vermaete N, Wolter P, Verhoef G, Gosselink R . Physical activity and physical fitness in lymphoma patients before, during, and after chemotherapy: a prospective longitudinal study. Ann Hematol. 2013; 93(3):411-24. DOI: 10.1007/s00277-013-1881-3. View

. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med. 2002; 166(1):111-7. DOI: 10.1164/ajrccm.166.1.at1102. View

Hamada R, Kondo T, Harada K, Murao M, Miyasaka J, Yoshida M . Evaluation of indices for predicting recovery of exercise tolerance in patients surviving allogenic hematopoietic stem cell transplantation. Support Care Cancer. 2022; 30(5):4027-4034. DOI: 10.1007/s00520-022-06822-z. View

Winkelmann M, Blumenberg V, Rejeski K, Quell C, Bucklein V, Ingenerf M . Predictive value of pre-infusion tumor growth rate for the occurrence and severity of CRS and ICANS in lymphoma under CAR T-cell therapy. Ann Hematol. 2023; 103(1):259-268. DOI: 10.1007/s00277-023-05507-9. View

Iacoboni G, Simo M, Villacampa G, Catala E, Carpio C, Diaz-Lagares C . Prognostic impact of total metabolic tumor volume in large B-cell lymphoma patients receiving CAR T-cell therapy. Ann Hematol. 2021; 100(9):2303-2310. DOI: 10.1007/s00277-021-04560-6. View

Vercellino L, Di Blasi R, Kanoun S, Tessoulin B, Rossi C, DAveni-Piney M . Predictive factors of early progression after CAR T-cell therapy in relapsed/refractory diffuse large B-cell lymphoma. Blood Adv. 2020; 4(22):5607-5615. PMC: 7686887. DOI: 10.1182/bloodadvances.2020003001. View

10.

Neelapu S . Managing the toxicities of CAR T-cell therapy. Hematol Oncol. 2019; 37 Suppl 1:48-52. DOI: 10.1002/hon.2595. View

11.

Nakamura N, Jo T, Arai Y, Kitawaki T, Nishikori M, Mizumoto C . Clinical Impact of Cytokine Release Syndrome on Prolonged Hematotoxicity after Chimeric Antigen Receptor T Cell Therapy: KyoTox A-Score, a Novel Prediction Model. Transplant Cell Ther. 2024; 30(4):404-414. DOI: 10.1016/j.jtct.2024.01.073. View

12.

Sidana S, Dueck A, Thanarajasingam G, Griffin J, Thompson C, Durani U . Longitudinal Patient Reported Outcomes with CAR-T Cell Therapy Versus Autologous and Allogeneic Stem Cell Transplant. Transplant Cell Ther. 2022; 28(8):473-482. PMC: 9357185. DOI: 10.1016/j.jtct.2022.05.004. View

13.

Hayakawa J, Miyamura D, Kimura S, Gomyo A, Tamaki M, Akahoshi Y . Negative impact of chronic graft-versus-host disease and glucocorticoid on the recovery of physical function after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2018; 54(7):994-1003. DOI: 10.1038/s41409-018-0365-4. View

14.

Gardner R, Ceppi F, Rivers J, Annesley C, Summers C, Taraseviciute A . Preemptive mitigation of CD19 CAR T-cell cytokine release syndrome without attenuation of antileukemic efficacy. Blood. 2019; 134(24):2149-2158. PMC: 6908832. DOI: 10.1182/blood.2019001463. View

15.

Nishikawa H, Goto M, Fukunishi S, Asai A, Nishiguchi S, Higuchi K . Cancer Cachexia: Its Mechanism and Clinical Significance. Int J Mol Sci. 2021; 22(16). PMC: 8395185. DOI: 10.3390/ijms22168491. View

16.

Schubert M, Schmitt M, Wang L, Ramos C, Jordan K, Muller-Tidow C . Side-effect management of chimeric antigen receptor (CAR) T-cell therapy. Ann Oncol. 2020; 32(1):34-48. DOI: 10.1016/j.annonc.2020.10.478. View

17.

Murao M, Kondo T, Hamada R, Miyasaka J, Matsushita M, Otagaki A . Minimal important difference of the 6-minute walk test after allogenic hematopoietic stem cell transplantation. Disabil Rehabil. 2023; 46(15):3449-3456. DOI: 10.1080/09638288.2023.2246013. View

18.

Santomasso B, Nastoupil L, Adkins S, Lacchetti C, Schneider B, Anadkat M . Management of Immune-Related Adverse Events in Patients Treated With Chimeric Antigen Receptor T-Cell Therapy: ASCO Guideline. J Clin Oncol. 2021; 39(35):3978-3992. DOI: 10.1200/JCO.21.01992. View

19.

Wang J, Hu Y, Yang S, Wei G, Zhao X, Wu W . Role of Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Predicting the Adverse Effects of Chimeric Antigen Receptor T Cell Therapy in Patients with Non-Hodgkin Lymphoma. Biol Blood Marrow Transplant. 2019; 25(6):1092-1098. DOI: 10.1016/j.bbmt.2019.02.008. View

20.

Kiefer T, Luders C, Voller H, Daeschlein G . Rehabilitation of patients after CAR T-cell therapy. Experiences on 5 patients. Transpl Immunol. 2022; 76:101770. DOI: 10.1016/j.trim.2022.101770. View