Sequential CD19 and BCMA‐specific CAR T‐cell treatment elicits sustained remission of relapsed and/or refractory myeloma

Autor: Depei Wu, Xiaolan Shi, Guanghua Chen, Song Jin, Lingzhi Yan, Nan Xu, Chengcheng Fu, Xiaming Zhu, Ming-Qing Zhu, Su Qu, Ying Yao, Huirong Chang, Jin Zhou, Weiqin Yao, Jingjing Shang, Liqing Kang, Lei Yu
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
0301 basic medicine
Oncology
Cancer Research
efficacy
Immunotherapy
Adoptive
0302 clinical medicine
Multiple myeloma
Original Research
Receptors
Chimeric Antigen
biology
Middle Aged
Prognosis
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Survival Rate
multiple myeloma
Tolerability
030220 oncology & carcinogenesis
Toxicity
relapsed and/or refractory
Female
Cart
safety
medicine.medical_specialty
Antigens
CD19
lcsh:RC254-282
CD19
03 medical and health sciences
Antigen
Refractory
Internal medicine
medicine
Humans
Radiology
Nuclear Medicine and imaging
B-Cell Maturation Antigen
Aged
Salvage Therapy
business.industry
Clinical Cancer Research
chimeric antigen receptor T (CAR T) cell
medicine.disease
Chimeric antigen receptor
030104 developmental biology
Drug Resistance
Neoplasm
biology.protein
dose‐escalation
Neoplasm Recurrence
Local
business
Follow-Up Studies
Zdroj: Cancer Medicine, Vol 10, Iss 2, Pp 563-574 (2021)
Cancer Medicine
ISSN: 2045-7634
Popis: The low rate of durable response against relapsed and/or refractory multiple myeloma (RRMM) in recent studies indicates that chimeric antigen receptor T‐cell (CART) treatment is yet to be optimized. This study aims to investigate the safety and efficacy of sequential infusion of CD19‐CART and B‐cell maturation antigen (BCMA)‐CARTs for RRMM with a similar 3 + 3 dose escalation combined with a toxicity sentinel design. We enrolled 10 patients, among whom 7 received autologous infusion and 3 received allogeneic infusion. The median follow‐up time was 20 months. The most common grade 3/4 treatment‐emergent toxicities were hematological toxicities. Cytokine‐release syndrome (CRS) adverse reactions were grade 1/2 in 9 out of 10 subjects. No dose‐limited toxicity (DLT) was observed for BCMA‐CAR‐positive T cells ≤5 × 107/kg), while two patients with dose‐levels of 5–6.5 × 107/kg experienced DLTs. The overall response rate was 90% (five partial responses and four stringent complete responses). Three out of four patients with stringent complete responses to autologous CART had progression‐free survival for over 2 years. The three patients with allogeneic CART experienced disease progression within 2 months. These results evidence the sequential infusion's preliminarily tolerability and efficacy in RRMM, and present a simple and safe design applicable for the establishment of multiple CART therapy.
We conducted a pilot study to assess the feasibility of the sequential infusion of CD19 and B‐cell maturation antigen (BCMA)‐specific chimeric antigen receptor T‐cell (CART) for relapsed and/or refractory multiple myeloma treatment with a similar 3 + 3 dose escalation design. Translational Significance: The favorable and persistent responses against RRMM were observed in those patients with a combined infusion of autologous CD19‐CART and BCMA‐CART. The emergence of intolerant adverse event (neurotoxicity and sever CRS) was associated with increased dose level of BCMA‐CARTs infusion.
Databáze: OpenAIRE
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