Viral infection/reactivation during long-term follow-up in multiple myeloma patients with anti-BCMA CAR therapy

Wang, Di; Mao, Xia; Que, Yimei; Xu, Menglei; Cheng, Yuanbing; Huang, Liang; Wang, Jue; Xiao, Yi; Wen, Wang; Hu, Guang; Zhang, Shangkun; Zhang, Tongcun; Li, Chunrui; Zhou, Jianfeng

doi:10.1038/s41408-021-00563-8

Cited by 35 publications

(29 citation statements)

References 14 publications

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“…Interestingly, these results diverge from our initial hypothesis that BCMA+CAR-T recipients are less likely to seroconvert in response to SARS-CoV-2 vaccines and have an increased risk of viral infections and reactivations in comparison to recipients of CD19+CAR-T cells 6,32,33 . Though both CD19-and BCMAtargeting therapies eliminate antibody-producing B-cells, preservation of CD19 + populations may be essential in mounting humoral immune responses to SARS-CoV-2 vaccines, as suggested by the lower seropositivity rates among CD19-directed CAR-T recipients.…”

Section: Discussioncontrasting

confidence: 80%

Efficacy of SARS-CoV-2 primary and booster vaccine doses in CAR-T recipients

Abid

Uyemura

et al. 2022

Preprint

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While multiple studies have demonstrated diminished humoral response to vaccinations against COVID-19 in immunocompromised patients, data are limited in chimeric antigen receptor T-cell (CAR-T) recipients. In this systematic review, we identified 18 studies through a manual search of key databases that reported SARS-CoV-2 vaccine responses in 236 CAR-T recipients. This included data from 184 recipients of CD19-directed CAR-T and 29 BCMA- or CD138-directed CAR-T therapy. The pooled humoral response rate across 18 studies was 25.8% (61/236), irrespective of number of vaccine doses. The vaccine response rate among patients who only completed their primary vaccine series with 2 doses, was 27.6% across 15 studies (50/181). The pooled seroconversion rate after receiving a third or fourth dose of vaccine was 20% in 4 studies (11/55). Recipients of CD19-directed CAR-T products had a seroconversion rate of 19.2% (25/130) compared to 71.4% (20/28) among those who received BCMA- or CD138-directed therapies after completion of a primary course of vaccination. Given a high COVID-19 attributable mortality and blunted seroconversion rates in CAR-T recipients, these results provide guidance to cellular therapy centers in terms of identifying higher risk patients. In the setting of ongoing highly transmissible variants of concern, the results are hypothesis-generating in terms of potential for earlier utilization of novel strategies such as the use of monoclonal antibodies in those CAR-T recipients less likely to respond to vaccines.

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Section: Discussioncontrasting

confidence: 80%

Efficacy of SARS-CoV-2 primary and booster vaccine doses in CAR-T recipients

Abid

Uyemura

et al. 2022

Preprint

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“…Cytomegalovirus (CMV) reactivation (including Herpes virus) was reported in ~1-2% but the real incidence is not known since routine monitoring of CMV varies among centers. Most reported cases presented as CMV viremia whereas CMV disease was uncommon but has been increasingly reported with some fatal cases being described [31,34,35]. [36][37][38].…”

Section: Viral Infectionsmentioning

confidence: 99%

Infectious complications, immune reconstitution, and infection prophylaxis after CD19 chimeric antigen receptor T-cell therapy

Wudhikarn

Perales

2022

Bone Marrow Transplant

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CD19-targeted chimeric antigen receptor (CAR) T-cell becomes a breakthrough therapy providing excellent remission rates and durable disease control for patients with relapsed/refractory (R/R) hematologic malignancies. However, CAR T-cells have several potential side effects including cytokine release syndrome, neurotoxicities, cytopenia, and hypogammaglobulinemia. Infection has been increasingly recognized as a complication of CAR T-cell therapy. Several factors predispose CAR T-cell recipients to infection. Fortunately, although studies show a high incidence of infection post-CAR T-cells, most infections are manageable. In contrast to patients who undergo hematopoietic stem cell transplant, less is known about post-CAR T-cell immune reconstitution. Therefore, evidence regarding antimicrobial prophylaxis and vaccination strategies in these patients is more limited. As CAR T-cell therapy becomes the standard treatment for R/R B lymphoid malignancies, we should expect a larger impact of infections in these patients and the need for increased clinical attention. Studies exploring infection and immune reconstitution after CAR T-cell therapy are clinically relevant and will provide us with a better understanding of the dynamics of immune function after CAR T-cell therapy including insights into appropriate strategies for prophylaxis and treatment of infections in these patients. In this review, we describe infections in recipients of CAR T-cells, and discuss risk factors and potential mitigation strategies.

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“…And while outside the scope of this review, tools to improve the safety of BCMA CAR-T therapy will be as important in the long term as strategies to improve efficacy. These include the early use of immunosuppressive therapies to abrogate CRS and ICANS ( 125 – 127 ), enhanced bridging to lower the rare risk of Parkinsonian toxicities ( 128 , 129 ), closer attention to infections and infectious prophylaxis ( 130 – 134 ), and CAR design modifications to abrogate life-threatening or long-term toxicities ( 76 , 135 , 136 ). Strategies to facilitate outpatient infusions of BCMA CAR-T therapy and shorten hospital lengths of stay are similarly important avenues for research in the field ( 137 , 138 ).…”

Section: Discussionmentioning

confidence: 99%

Innovation in BCMA CAR-T therapy: Building beyond the Model T

2022

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Autologous chimeric antigen receptor T-cell (CAR-T) therapies targeting B-cell maturation antigen (BCMA) have revolutionized the field of multiple myeloma in the same way that the Ford Model T revolutionized the original CAR world a century ago. However, we are only beginning to understand how to improve the efficacy and usability of these cellular therapies. In this review, we explore three automotive analogies for innovation with BCMA CAR-T therapies: stronger engines, better mileage, and hassle-free delivery. Firstly, we can build stronger engines in terms of BCMA targeting: improved antigen binding, tools to modulate antigen density, and armoring to better reach the antigen itself. Secondly, we can improve “mileage” in terms of response durability through ex vivo CAR design and in vivo immune manipulation. Thirdly, we can implement hassle-free delivery through rapid manufacturing protocols and off-the-shelf products. Just as the Model T set a benchmark for car manufacturing over 100 years ago, idecabtagene vicleucel and ciltacabtagene autoleucel have now set the starting point for BCMA CAR-T therapy with their approvals. As with any emerging technology, whether automotive or cellular, the best in innovation and optimization is yet to come.

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Viral infection/reactivation during long-term follow-up in multiple myeloma patients with anti-BCMA CAR therapy

Cited by 35 publications

References 14 publications

Efficacy of SARS-CoV-2 primary and booster vaccine doses in CAR-T recipients

Efficacy of SARS-CoV-2 primary and booster vaccine doses in CAR-T recipients

Infectious complications, immune reconstitution, and infection prophylaxis after CD19 chimeric antigen receptor T-cell therapy

Innovation in BCMA CAR-T therapy: Building beyond the Model T

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