CAR-T cell therapy for multiple myeloma: a practical toolkit for treatment in Brazil

Hungria, Vania; Piérola, Ana Alfonso; Schmidt Filho, Jayr; Crusoe, Edvan; Magalhães Filho, Roberto José Pessoa de; Maiolino, Angelo; Rodríguez-Otero, Paula

doi:10.1016/j.htct.2022.08.002

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Brasil

Hematology, Transfusion and Cell Therapy

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Original article • Hematol., Transfus. Cell Ther. 45 (2) • Apr-Jun 2023 • https://doi.org/10.1016/j.htct.2022.08.002 copy

CAR-T cell therapy for multiple myeloma: a practical toolkit for treatment in Brazil

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Introduction

Chimeric antigen receptor T (CAR-T) cell therapy is an emerging treatment option for relapsed/refractory multiple myeloma (RRMM) that is a multi-step process involving various stakeholders. Appropriate education on the practical logistics is therefore paramount to ensure treatment success.

Methods

A group of key opinion leaders met to explore the key elements of setting up and running a CAR-T center in Brazil. For each step in the CAR-T cell therapy process, the experts agreed on basic requirements, gave their key recommendations from practical experience, and considered any remaining unanswered questions.

Results

This paper presents best-practice recommendations and advice on how to overcome common challenges for each step in the CAR-T cell therapy process, with a focus on the current situation in Brazil. Key themes throughout the process are collaboration within the multidisciplinary team and with the referring physician, along with communication and education for patients and their caregivers.

Conclusion

We believe that the expert insights presented in this paper, in particular on optimal patient selection and timing of CAR-T cell therapy, will deepen understanding of the CAR-T process and aid implementation of this novel therapy for patients with RRMM in Brazil.

Keywords
CAR-T cell therapy; Multiple myeloma; Bridging therapy; Immunotherapy; BCMA

Evaluation	Expert recommendations
At baseline for patient selection
Full blood count Hemoglobin ≥8.0 g/dL (≥5 mmol/L) Platelets ≥50 × 10⁹/L Lymphocyte count ≥0.3 × 10⁹/L Absolute neutrophil count ≥0.75 × 10⁹/L	Important for selecting the right patient. These tests can be performed by the referring physician
Full biochemistry Aspartate aminotransferase and alanine aminotransferase ≤3.0 × upper limit of normal (ULN) Creatinine clearance ≥40 mL/min/1.73 m² Total bilirubin ≤2.0 × ULN Corrected serum calcium ≤12.5 mg/dL (≤3.1 mmol/L) or free ionized calcium ≤6.5 mg/dl (≤1.6 mmol/L)
Cardiac assessment
Respiratory assessment
Before leukapheresis
Disease evaluation	Can take place after the leukapheresis slot has been booked
Viral serology	Mandatory before leukapheresis but does not need to be repeated before infusion
No major surgery ≤2 weeks prior to leukapheresis
No live, attenuated vaccines ≤4 weeks prior to leukapheresis
No supplemental oxygen use to maintain adequate oxygenation
No new arrhythmia or other cardiac adverse events
No evidence of serious active viral, bacterial, or uncontrolled systemic fungal infection
Full blood count
Before lymphodepleting chemotherapy/infusion
Clinical laboratory values required for enrollment, with the following exception: lymphocyte count of ≥0.3 × 10⁹/L
Disease evaluation	Important if bridging therapy has taken place. This will be used to evaluate the CAR-T cell therapy efficacy
Echocardiogram or multigated acquisition scan for subjects who receive bridging therapy that includes agents with known cardiac toxicity
No active Grade 3 toxicity to any bridging therapy
No signs of active infection

Similarities	Differences
A similar work-up of blood counts and viral serology tests are required	ASCT is approved in frontline, while CAR-T is currently only approved in patients previously exposed to a PI, IMiD and anti-CD38 mAb
The same leukapheresis machine can be used	Baseline neurological evaluation is required for CAR-T but not ASCT
The same cardiological and respiratory work up can be performed with echocardiogram +/- respiratory test if the patient has respiratory problems	There are clear guidelines for contraindications of ASCT, but these are not currently as well defined for CAR-T
Experience from the multidisciplinary team for transplantation can be leveraged for CAR-T cell therapy and the care of patients with MM	Patients undergo ASCT with low burden of disease after induction therapy. Burden of disease may be higher before CAR-T, but this has been associated with worse adverse events
	In contrast to cells for ASCT, CAR-T cells are considered a drug, which requires involvement from pharmacists
	Adverse event profiles
	The patient journey, including time spent as an inpatient

Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular (ABHH) R. Dr. Diogo de Faria, 775 cj 133, 04037-002, São Paulo / SP - Brasil - São Paulo - SP - Brazil
E-mail: htct@abhh.org.br

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[1] ⁎ Corresponding author at: Department of Hematology, Clínica Universidad de Navarra, Pamplona, Spain, Department of Hematology, Clínica Universidad de Navarra, Pamplona, Spain, E-mail address: paurodriguez@unav.es (P. Rodríguez-Otero).