scholarly journals Efficacy of Humanized Anti-BCMA CAR T Cell Therapy in Relapsed/Refractory Multiple Myeloma Patients With and Without Extramedullary Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Haobin Deng ◽  
Meijing Liu ◽  
Ting Yuan ◽  
Huan Zhang ◽  
Rui Cui ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cell ◽  
Cell Therapy ◽  
M Protein ◽  
T Cell Therapy ◽  
Hematopoietic Stem ◽  
Extramedullary Disease ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

In recent years, many new treatments for relapsed/refractory (R/R) multiple myeloma (MM) have improved patient prognosis, but the prognosis of patients with extramedullary MM is still particularly poor. Therefore, more efficacious therapies and novel strategies are urgently needed for these patients. The aim of this study was to observe and compare the efficacy and safety of humanized anti-B cell maturation antigen (anti-BCMA) chimeric antigen receptor (CAR) T cell therapy in R/R MM patients with and without extramedullary disease. Seven R/R MM patients with extramedullary disease and 13 without extramedullary disease received humanized anti-BCMA CAR T cell therapy. The overall response rate was not different between patients with and without extramedullary disease. There was no difference in the progression-free survival (PFS) or overall survival (OS) rates between the two groups at 180 days, but the PFS and OS rates in patients with extramedullary disease were lower at 360 days than those in patients without extramedullary disease. Although some patients with extramedullary disease experienced further disease progression, their M protein level did not increase. We did not see this change trend of M protein in patients without extramedullary disease. However, this was not observed in patients without extramedullary disease. Among patients who responded to CAR T cell therapy, the grades of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxic syndrome (ICANS) were much higher among patients with extramedullary disease. In summary, R/R MM patients with extramedullary disease could benefit from humanized anti-BCMA CAR T cell therapy in the short term, although the CRS and ICANS grades were much higher in patients with extramedullary disease. Therefore, anti-BCMA CAR T cell therapy allows for a remission time for R/R MM patients with extramedullary disease, which could be maintained by bridging hematopoietic stem cell transplantation, radiotherapy, and other therapies.Clinical Trial Registrationhttp://www.chictr.org.cn/index.aspx, identifiers ChiCTR1800017051 and ChiCTR2000033925.

scholarly journals Lenalidomide enhances the efficacy of anti-BCMA CAR-T treatment in relapsed/refractory multiple myeloma: a case report and revies of the literature

2021 ◽  
Author(s):  
Guoxing Zhao ◽  
Runhong Wei ◽  
Lei Feng ◽  
Yi Wu ◽  
Feng He ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cell ◽  
Cell Therapy ◽  
Proteasome Inhibitors ◽  
Symptomatic Treatment ◽  
T Cell Therapy ◽  
Hematopoietic Stem ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

AbstractWe report successful clinical experience using anti-BCMA CAR-T combined with lenalidomide in a patient who was refractory to a previous CAR-T treatment. The patient was a 51-year-old man, and was diagnosed with IgD-λ multiple myeloma(MM) in October 2015. 10 courses of chemotherapy including immunomodulators and proteasome inhibitors were used for remission and autologous hematopoietic stem cell transplantation was performed. MM relapsed after 12 months of remission. His disease continued to progress after multiple chemotherapy regimens, mouse anti-BCMA CAR-T and human-derived anti-BCMA CAR-T therapy. After a conditioning chemotherapy regimen of fludarabine and cyclophosphamide, patient took lenalidomide on day -1 and human-derived anti-BCMA CAR-T cells were infused on the next day. He suffered grade 2 cytokine-releasing syndrome(CRS) and grade 3 myelosuppression after infusion, and were resolved after symptomatic treatment. Very good partial response (VGPR) was achieved 14 days after CAR-T treatment, and had been maintained for more than 8 months. We demonstrated for the first time in patients that anti-BCMA CAR-T cell therapy combined with lenalidomide is feasible and effective in the treatment of RRMM. It provides a new strategy for RRMM patients who do not respond to anti-BCMA CAR-T cell therapy alone, and the adverse event is reversible.

scholarly journals Anti-BCMA CAR-T Cell Therapy in Relapsed/Refractory Multiple Myeloma Patients With Extramedullary Disease: A Single Center Analysis of Two Clinical Trials

2021 ◽  
Vol 12 ◽  
Author(s):  
Yimei Que ◽  
Menglei Xu ◽  
Yanjie Xu ◽  
Varlene Daniela Fernandes Almeida ◽  
Li Zhu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
T Cell ◽  
Complete Remission ◽  
Cell Therapy ◽  
T Cell Therapy ◽  
Extramedullary Disease ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

BackgroundThe prognosis of relapsed/refractory multiple myeloma (RRMM) patients with the extramedullary disease was significantly poor. Extramedullary multiple myeloma (EMM) patients gained limited benefits from traditional drugs. Anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy seems to be a promising approach to treat RRMM patients. However, very few clinical studies are designed for EMM. Our study aimed to compare and assess the safety, efficacy, and pharmacokinetics of anti-BCMA CAR-T cell therapy in EMM and non-EMM.MethodsThe results from published anti-BCMA CAR-T clinical trials, in which raw data of EMM patients were available, were reviewed and summarized. Two trials conducted in our clinical centers were analyzed and presented with detailed data.ResultsAccording to published anti-BCMA CAR-T clinical trials, the ORR of EMM ranged from 57% to 100%, with the complete remission (CR) rate of 29% to 60%. Between February 22, 2017, and September 26, 2019, a total of 61 subjects (EMM 25; non-EMM 36) received anti-BCMA CAR-T cell infusion. The data-cutoff date was April 1, 2021. There were no statistical differences between EMM and non-EMM groups in adverse events (AEs), including cytokine release syndrome (CRS). The most common AEs of grade ≥ 3 in both groups were hematologic toxicities. There was no significant difference in the objective response rate (ORR) and ≥ complete remission (CR) rate between both groups. However, the ≥ CR rate of the EMM group was lower than the non-EMM group receiving the fully human anti-BCMA CAR-T cell therapy (p = 0.026). The median progression-free survival (PFS) for EMM and the non-EMM group was 121 days and 361 days, respectively (p = 0.001). The median overall survival (OS) for EMM and the non-EMM group was 248 days and 1024 days, respectively (p = 0.005). The Cmax and AUC0-28d for EMM group were lower than non-EMM group (Cmax, p = 0.016; AUC0-28d, p = 0.016). Extramedullary disease was an independent prognostic risk factor for PFS (hazard ratio, 2.576; 95% CI, 1.343 to 4.941; p = 0.004) and OS (hazard ratio, 2.312; 95% CI, 1.165 to 4.592; p = 0.017) in RRMM patients receiving anti-BCMA CAR-T cell therapy.ConclusionsBased on our results, EMM patients could benefit from the two anti-BCMA CAR products, although they had a shorter PFS and OS compared with non-EMM patients.Clinical Trial Registrationhttp://www.chictr.org.cn, identifier ChiCTR-OPC-16009113 and ChiCTR1800018137.

Siglec-6 is a novel target for CAR T-cell therapy in acute myeloid leukemia (AML)

Blood ◽  
2021 ◽  
Author(s):  
Hardikkumar Jetani ◽  
Almudena Navarro-Bailón ◽  
Marius Maucher ◽  
Silke Frenz ◽  
Christina Mathilde Verbruggen ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Therapy ◽  
T Cell Therapy ◽  
Hematopoietic Stem ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
Novel Target

Acute myeloid leukemia (AML) is attractive for the development of CAR T-cell immunotherapy because AML blasts are susceptible to T-cell-mediated elimination. Here, we introduce sialic-acid-binding immunoglobulin-like lectin (Siglec)-6 as a novel target for CAR T-cells in AML. We designed a Siglec-6-specific CAR with a targeting-domain derived from a human monoclonal antibody JML‑1. We found that Siglec-6 is prevalently expressed on AML cell lines and primary AML blasts, including the subpopulation of AML stem cells. Treatment with Siglec-6-CAR T-cells confers specific anti-leukemia reactivity that correlates with Siglec-6-expression in pre-clinical models, including induction of complete remission in a xenograft AML model in immunodeficient mice (NSG/U937). In addition, we confirmed Siglec-6-expression on transformed B-cells in chronic lymphocytic leukemia (CLL) and show specific anti-CLL-reactivity of Siglec-6-CAR T-cells in vitro. Of particular interest, we found that Siglec-6 is not detectable on normal hematopoietic stem and progenitor cells (HSC/P) and that treatment with Siglec-6-CAR T-cells does not affect their viability and lineage differentiation in colony-formation assays. These data suggest that Siglec-6-CAR T-cell therapy may be used to effectively treat AML without a need for subsequent allogeneic hematopoietic stem cell transplantation. In mature normal hematopoietic cells, we detected Siglec-6 in a proportion of memory (and naïve) B-cells and basophilic granulocytes, suggesting the potential for limited on-target/off-tumor reactivity. The lacking expression of Siglec-6 on normal HSC/P is a key differentiator from other Siglec-family members (e.g. Siglec-3=CD33) and other CAR target antigens, e.g. CD123, that are under investigation in AML and warrants the clinical investigation of Siglec-6-CAR T-cell therapy.

A phase 1 multicenter study evaluating KITE-585, an autologous anti-BCMA CAR T-cell therapy, in patients with relapsed/refractory multiple myeloma.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. TPS3103-TPS3103 ◽  
Author(s):  
Robert F. Cornell ◽  
Frederick Lundry Locke ◽  
Michael Russell Bishop ◽  
Robert Z. Orlowski ◽  
Sarah Marie Larson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cell ◽  
Cell Therapy ◽  
Multicenter Study ◽  
Phase 1 ◽  
T Cell Therapy ◽  
Refractory Multiple Myeloma ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T
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