AUTHOR=Li Hujun , Zhao Lina , Sun Zengtian , Yao Yue , Li Li , Wang Jiaojiao , Hua Tian , Ji Shengwei , Wang Shiyuan , Cheng Hai , Shi Ming , Li Zhenyu , Zeng Lingyu , Wu Qingyun , Qiao Jianlin , Chen Chong , Zheng Junnian , Cao Jiang , Xu Kailin 

TITLE=Prolonged hematological toxicity in patients receiving BCMA/CD19 CAR-T-cell therapy for relapsed or refractory multiple myeloma

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1019548

DOI=10.3389/fimmu.2022.1019548

ISSN=1664-3224

ABSTRACT=<p>Although chimeric antigen receptor T (CAR-T) cell therapy has been indicated to be effective in treating relapsed or refractory multiple myeloma (R/R MM), severe hematological toxicity (HT) remains an intractable issue. This study enrolled 54 patients with R/R MM following combined infusion of anti-CD19 and anti-BCMA CAR-T cells. The results showed that the rates of severe cytopenia were high, including severe neutropenia (28/54, 52%), severe anemia (15/54, 28%), and severe thrombocytopenia (18/54, 33%). Moreover, the incidence of prolonged HT (PHT) on Day 28 post-infusion was 52% (28/54), including 46% for severe neutropenia, 30% for severe anemia, and 31% for severe thrombocytopenia. Patients with PHT had a poorer median progression-free survival (PFS) and overall survival (OS) than patients without PHT (<italic>P</italic>=0.011; <italic>P</italic>=0.007). Furthermore, Cox regression analyses showed that PHT was an independent risk factor for PFS and OS. Univariate analyses showed that IFNγ (OR: 1.046; 95% CI: 1.002-1.093, <italic>P</italic>=0.042) and severe HT after lymphodepletion chemotherapy (OR: 0.082; 95% CI: 0.017-0.404; <italic>P</italic>=0.002) were independent risk factors for PHT. In conclusion, these results indicated that PHT was associated with poor outcomes following CAR-T-cell therapy in MM patients. Early detection and management of PHT would be beneficial for the prevention of life-threatening complications and improvement in the survival of patients after CAR-T-cell therapy.</p><sec><title>Clinical trial registration</title><p>This trial was registered on 1 May 2017 at <uri xlink:href="http://www.chictr.org.cn" xmlns:xlink="http://www.w3.org/1999/xlink">http://www.chictr.org.cn</uri> as ChiCTR-OIC-17011272.</p></sec>