B cell maturation antigen–specific CAR T cells are clinically active in multiple myeloma

Cohen, Adam D.; Garfall, Alfred L.; Stadtmauer, Edward A.; Melenhorst, J. Joseph; Lacey, Simon F.; Lancaster, Eric; Vogl, Dan T.; Weiss, Brendan M.; Dengel, Karen; Nelson, Annemarie; Plesa, Gabriela; Chen, Fang; Davis, Megan M.; Hwang, Wei–Ting; Young, Regina M.; Brogdon, Jennifer L.; Isaacs, Randi; Pruteanu-Malinici, Iulian; Siegel, Don L.; Levine, Bruce L.; June, Carl H.; Milone, Michael C.

doi:10.1172/jci126397

Cited by 575 publications

(619 citation statements)

References 40 publications

Supporting

Mentioning

551

Contrasting

Unclassified

Order By: Relevance

“…The baseline characteristics of the included studies are listed in Table 1. A total of 314 patients were included in the 18 studies, [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48] all of which were single-arm early phase studies that included only patients with RRMM (17 studies) or newly diagnosed myeloma (1 study). Patients included in RRMM studies were heavily pretreated and received a median of 6 prior lines of treatment (proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, 1-2 autologous stem cell transplants).…”

Section: Patient and Study Characteristicsmentioning

confidence: 99%

“…32,36 Most studies used fludarabine and cyclophosphamide for lymphodepletion while one study used busulfan and cyclophosphamide 46 and one study used cyclophosphamide only. 42 Most studies included patients who underwent autologous stem cell transplantation as part of prior treatment while transplant data were lacking in six studies. 35,41,[43][44][45]47 One study in patients with newly diagnosed myeloma applied CAR T-cell therapy after a tandem transplant approach.…”

Section: Patient and Study Characteristicsmentioning

confidence: 99%

“…Additionally, the risk of evidence imprecision F I G U R E 1 shows the PRISMA flow diagram of the study selection process. Out of 18 identified studies, [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48] three were included only in the qualitative review because they evaluated CAR T products that, in addition to BCMA, targeted other antigens such as CD19 and CD38. [46][47][48] The remaining 15 studies were included in the quantitative systematic review and meta-analysis [Colour figure can be viewed at wileyonlinelibrary.com]…”

Section: Patient and Study Characteristicsmentioning

confidence: 99%

“…Fifteen studies and 285 patients with RRMM were included in the pooled analysis of efficacy and safety of anti-BCMA CAR T cells. [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] The pooled proportion of overall response was 82% with a 95% confidence interval (CI) of 74%-88% (I 2 = 44%; Figure 2A). This was pooled from all 15 studies involving 264 evaluable patients of whom 219 showed a response lasting a median of 10 months.…”

Section: Efficacymentioning

confidence: 99%

See 3 more Smart Citations

B cell maturation antigen‐specific chimeric antigen receptor T cells for relapsed or refractory multiple myeloma: A meta‐analysis

Gagelmann

Ayuk

Atanackovic

2020

European J of Haematology

View full text Add to dashboard Cite

Introduction Chimeric antigen receptor (CAR) T cells targeting B cell maturation antigen (BCMA) have shown impressive results in clinical studies for relapsed/refractory multiple myeloma (RRMM). We performed a systematic literature review to summarize the current body of evidence on the role of anti‐BCMA CAR T cells for RRMM. Objectives and Methods Fifteen studies comprising a total of 285 patients with heavily pretreated RRMM were included using a conventional meta‐analysis. Main efficacy outcomes were response, relapse, and survival. Safety outcomes were cytokine release syndrome (CRS) and neurotoxicity. Results Anti‐BCMA CAR T cells resulted in a pooled overall response of 82% (95% confidence interval [CI], 74%‐88%) and complete response of 36% (24%‐50%). Higher CAR+ cell doses were associated with higher response rates. The pooled relapse rate of responders was 45% (27%‐64%), and median progression‐free survival was 10 months. Present extramedullary disease did not show worse outcome. Severe CRS grades 3‐4 and neurotoxicity occurred in 15% (10%‐23%) and 18% (10%‐31%). Conclusion Anti‐BCMA CAR T cells showed high response rates, even in patients with present extramedullary disease, while relapse occurred in half of the patients who achieved a response. Larger studies with longer follow‐up especially evaluating the association of response and survival are needed.

show abstract

Section: Patient and Study Characteristicsmentioning

confidence: 99%

Section: Patient and Study Characteristicsmentioning

confidence: 99%

Section: Patient and Study Characteristicsmentioning

confidence: 99%

Section: Efficacymentioning

confidence: 99%

See 2 more Smart Citations

B cell maturation antigen‐specific chimeric antigen receptor T cells for relapsed or refractory multiple myeloma: A meta‐analysis

Gagelmann

Ayuk

Atanackovic

2020

European J of Haematology

View full text Add to dashboard Cite

show abstract

“…Toxicities were notable, with 22 patients developing CRS, including Grade 3 according to the Penn scale in eight patients, all treated at the higher cell dose. ICANS was observed in eight patients (32%) and was severe in three, with resolution of all toxicities . Again, responses were not correlated with intensity of BCMA expression on MM cells, but with in vivo CAR T‐cell expansion.…”

Section: Targeting Beyond Cd19 In B‐cell Malignancies: Multiple Myelomamentioning

confidence: 94%

Updates on CAR T‐cell therapy in B‐cell malignancies

Jacoby

Shahani

Shah

2019

Immunological Reviews

View full text Add to dashboard Cite

By increasing disease‐free survival and offering the potential for long‐term cure, chimeric antigen receptor (CAR) T‐cell therapy has dramatically expanded therapeutic options among those with high‐risk B‐cell malignancies. As CAR T‐cell utilization evolves however, novel challenges are generated. These include determining how to optimally integrate CAR T cells into standard of care and overcoming mechanisms of resistance to CAR T‐cell therapy, such as evolutionary stress induced on cancer cells leading to immunophenotypic changes that allow leukemia to evade this targeted therapy. Compounding these challenges are the limited ability to determine differences between various CAR T‐cell constructs, understanding the generalizability of trial outcomes from multiple sites utilizing unique CAR manufacturing strategies, and comparing distinct criteria for toxicity grading while defining optimal management. Additionally, as understanding of CAR behavior in humans has developed, strategies have appropriately evolved to proactively mitigate toxicities. These challenges offer complimentary insights and guide next steps to enhance the efficacy of this novel therapeutic modality. With a focus on B‐cell malignancies as the paradigm for effective CAR T‐cell therapy, this review describes advances in the field as well as current challenges and future directions.

show abstract

Future prospects of chimeric antigen receptor T‐cell therapy for multiple myeloma

et al. 2019

View full text Add to dashboard Cite

B cell maturation antigen–specific CAR T cells are clinically active in multiple myeloma

Cited by 575 publications

References 40 publications

B cell maturation antigen‐specific chimeric antigen receptor T cells for relapsed or refractory multiple myeloma: A meta‐analysis

B cell maturation antigen‐specific chimeric antigen receptor T cells for relapsed or refractory multiple myeloma: A meta‐analysis

Updates on CAR T‐cell therapy in B‐cell malignancies

Future prospects of chimeric antigen receptor T‐cell therapy for multiple myeloma

Contact Info

Product

Resources

About