BCMA-Targeted CAR T-cell Therapy plus Radiotherapy for the Treatment of Refractory Myeloma Reveals Potential Synergy

Eric L Smith, Sham Mailankody, Mette Staehr, Xiuyan Wang, Brigitte Senechal, Terence J Purdon, Anthony F Daniyan, Mark B Geyer, Aaron D Goldberg, Elena Mead, Bianca D Santomasso, Jonathan Landa, Andreas Rimner, Isabelle Riviere, Ola Landgren, Renier J Brentjens

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Abstrakt

We present a case of a patient with multiply relapsed, refractory myeloma whose clinical course showed evidence of a synergistic abscopal-like response to chimeric antigen receptor (CAR) T-cell therapy and localized radiotherapy (XRT). Shortly after receiving B-cell maturation antigen (BCMA)-targeted CAR T-cell therapy, the patient required urgent high-dose steroids and XRT for spinal cord compression. Despite the steroids, the patient had a durable systemic response that could not be attributed to XRT alone. Post-XRT findings included a second wave of fever and increased CRP and IL6, beginning 21 days after CAR T cells, which is late for cytokine-release syndrome from CAR T-cell therapy alone on this trial. Given this response, which resembled cytokine-release syndrome, immediately following XRT, we investigated changes in the patient's T-cell receptor (TCR) repertoire over 10 serial time points. Comparing T-cell diversity via Morisita's overlap indices (CD ), we discovered that, although the diversity was initially stable after CAR T-cell therapy compared with baseline (CD = 0.89-0.97, baseline vs. 4 time points after CAR T cells), T-cell diversity changed after the conclusion of XRT, with >30% newly expanded TCRs (CD = 0.56-0.69, baseline vs. 4 time points after XRT). These findings suggest potential synergy between radiation and CAR T-cell therapies resulting in an abscopal-like response.

OriginalsprogEngelsk
TidsskriftCancer Immunology Research
Vol/bind7
Udgave nummer7
Sider (fra-til)1047-1053
ISSN2326-6066
DOI
StatusUdgivet - jul. 2019
Udgivet eksterntJa

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Bibliografisk note

©2019 American Association for Cancer Research.

Citationsformater

Smith, E. L., Mailankody, S., Staehr, M., Wang, X., Senechal, B., Purdon, T. J., Daniyan, A. F., Geyer, M. B., Goldberg, A. D., Mead, E., Santomasso, B. D., Landa, J., Rimner, A., Riviere, I., Landgren, O., & Brentjens, R. J. (2019). BCMA-Targeted CAR T-cell Therapy plus Radiotherapy for the Treatment of Refractory Myeloma Reveals Potential Synergy. Cancer Immunology Research, 7(7), 1047-1053. https://doi.org/10.1158/2326-6066.CIR-18-0551