Infectious complications in patients with relapsed refractory multiple myeloma after BCMA CAR T-cell therapy

Kambhampati, Swetha; Sheng, Ying; Huang, Chiung‐Yu; Bylsma, Sophia; Lo, Mimi; Kennedy, Vanessa E.; Natsuhara, Kelsey; Martin, Thomas G.; Wolf, Jeffrey L.; Shah, Nina; Wong, Sandy W.

doi:10.1182/bloodadvances.2020004079

Cited by 67 publications

(94 citation statements)

References 21 publications

(32 reference statements)

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“…Comparing our SOC infection data with the data from Kambhampati et al, 25 we had a similar proportion of patients affected by infection (54% vs 53%) but a higher number of infections within 100 days of CAR T-cell infusion (46 vs 25) and more patients with severe infection (23% vs 6%) despite antibiotic prophylaxis. Institutional guidelines were similar across the 3 centers in our study with all utilizing antiviral, antibiotic, antifungal, and Pneumocystis pneumonia prophylaxis ( supplemental Table 1 ).…”

Section: Discussionsupporting

confidence: 73%

“…Notably, none of the severe infections within our patients would have been re-classified as moderate based on the definition used by Kambhampati et al. 25 Further, we showed that earlier infections in the first 30 days after ide-cel were typically bacterial (68%) and severe in nature (50%), while later infections between days 31 and 100 were more likely to be moderate by definition and were more evenly distributed between bacterial (50%) and viral (42%) causes. Compared with KarMMa, fewer of our patients experienced an infection (54% vs 69% on trial) but a similar proportion had severe infection (23% vs 22% on trial).…”

Section: Discussionmentioning

confidence: 95%

“…Kambhampati et al recently published on infectious complications within 1 year after anti-BCMA CAR T-cell therapy. 25 Their retrospective single-center 55-patient study exclusively included patients on clinical trials: 42% bb2121 (ide-cel), 13% bb21217 (ide-cel with PI3K inhibitor incubation), 15% JNJ-4528 (cilta-cel), and 31% JCARH125 (orvacabtagene autoleucel, now abandoned). Authors identified 47 infections in 29 patients (53%) with 53% of infections in the first 100 days, 40% bacterial, 53% viral, 92% mild to moderate, and 68% involving the respiratory tract.…”

Section: Discussionmentioning

confidence: 99%

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Early cytopenias and infections after standard of care idecabtagene vicleucel in relapsed or refractory multiple myeloma

et al. 2022

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Idecabtagene vicleucel (ide-cel) was FDA approved in March 2021 for the treatment of relapsed/refractory multiple myeloma (RRMM) after 4 lines of therapy. On the KarMMa trial, grade ≥3 cytopenias and infections were common. We sought to characterize cytopenias and infections within 100 days after ide-cel in the standard of care (SOC) setting. This multi-center retrospective study included 52 patients who received SOC ide-cel; 47 reached day 90 follow-up. Data was censored at day 100. Grade ≥3 cytopenia was present among 65% of patients at day 30 and 40% of patients at day 90. Granulocyte colony stimulating factor (G-CSF) was administered to 88%, packed red blood cell (pRBC) transfusions to 63%, platelet transfusions to 42%, thrombopoietin (TPO) agonists to 21%, intravenous immunoglobulin (IVIG) to 13%, and CD34+ stem cell boosts to 8%. At day 100, 19% and 13% of patients had ongoing use of TPO agonists and G-CSF, respectively. Infections occurred in 54% of patients and were grade ≥3 in 23%. Earlier infections in the first 30 days were typically bacterial (68%) and severe (50%). Later infections between days 31 - 100 were 50% bacterial and 42% viral; only 13% were grade ≥3. On univariate analysis, high pre-CAR-T marrow myeloma burden (>/= 50%), circulating plasma cells at pre-lymphodepletion (LD), and grade ≥3 anemia at pre-LD were associated with grade ≥3 cytopenia at both days 30 and 90. Longer time from last bridging treatment to LD was the only significant risk factor for infection.

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Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

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Early cytopenias and infections after standard of care idecabtagene vicleucel in relapsed or refractory multiple myeloma

et al. 2022

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“…Unlike CD19 CAR T-cells, viral infection is the most common infectious complication followed by bacterial and fungal infections. In a recent report of 55 patients with R/R MM patients treated with BCMA CAR T-cells, 53% developed infection within the first 6 months (53% viral, 40% bacterial, and 6% fungal) [32]. Approximately half of the infectious events occurred within the first 100 days.…”

Section: Infections In Patients Who Undergo Cd19 Car T-cell Therapymentioning

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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“…Bispecific antibodies (bsAb) targeting novel antigens are a promising class of therapeutics for relapsed refractory multiple myeloma (RRMM). 1 , 2 Although hypogammaglobulinemia is expected due to plasma cell depletion, 3 , 4 , 5 little is known regarding the degree of humoral immunodeficiency and infectious complications with bsAb. We report on the kinetics of humoral deficiency among patients with RRMM treated with bsAb, the infectious complications, and response to COVID-19 immunization.…”

Section: Introductionmentioning

confidence: 99%

Kinetics of Humoral Immunodeficiency With Bispecific Antibody Therapy in Relapsed Refractory Multiple Myeloma

et al. 2022

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Infectious complications in patients with relapsed refractory multiple myeloma after BCMA CAR T-cell therapy

Cited by 67 publications

References 21 publications

Early cytopenias and infections after standard of care idecabtagene vicleucel in relapsed or refractory multiple myeloma

Early cytopenias and infections after standard of care idecabtagene vicleucel in relapsed or refractory multiple myeloma

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

Kinetics of Humoral Immunodeficiency With Bispecific Antibody Therapy in Relapsed Refractory Multiple Myeloma

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