Bilateral retinal detachment after chimeric antigen receptor T-cell therapy

Denton, Christopher; Gange, William S.; Abdel‐Azim, Hisham; Jodele, Sonata; Kapoor, Neena; Oberley, Matthew J.; Wong, Kenneth; Kim, Jonathan; Vercio, Abby; Moghaddampour, Parisah; Chalam, Kakarla V; Sierpina, David; Gardner, Rebecca; Pulsipher, Michael A.; Jensen, Michael C.; Nagiel, Aaron

doi:10.1182/bloodadvances.2020001450

Cited by 26 publications

(19 citation statements)

References 20 publications

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“…Our experience demonstrates the ability of BRT to effectively treat bulky symptomatic extramedullary leukemic disease in critical sites with minimal toxicity, in order to achieve disease control, and also to prevent potential CAR‐T‐associated organ toxicity. Similarly, BRT prior to and following CAR‐T in another B‐ALL patient provided local ocular disease control, permitting successful treatment 24 . In our case, the use of BRT targeting the heart was an effective strategy to mitigate potential cardiac toxicity in a tenuous patient.…”

Section: Resultsmentioning

confidence: 62%

“…Similarly, BRT prior to and following CAR-T in another B-ALL patient provided local ocular disease control, permitting successful treatment. 24 In our case, the use of BRT targeting the heart was an effective strategy to mitigate potential cardiac toxicity in a tenuous patient. This is the first report of cardiac and GI BRT in the pre-CAR setting for ALL, and supports future studies of BRT in R/R B-ALL patients with extramedullary involvement, to improve candidacy for CAR-T therapy and potentially reduce relative toxicity risk.…”

Section: Debulking and Brtmentioning

confidence: 73%

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Use of cardiac radiation therapy as bridging therapy to CAR‐T for relapsed pediatric B‐cell acute lymphoblastic leukemia

Márquez

Montiel-Esparza

Hui

et al. 2020

Pediatric Blood & Cancer

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The use of radiotherapy as bridging therapy to chimeric antigen receptor T-cell therapy (CAR-T) in pre-B acute lymphoblastic leukemia (B-ALL) has been minimally explored. Here, we present a boy with BALL who relapsed after allogeneic bone marrow transplant with disseminated disease, including significant symptomatic cardiovascular and gastrointestinal (GI) involvement. The cardiac and GI leukemic infiltrates were successfully treated with bridging radiation therapy (BRT) prior to CART infusion. Using this approach, he successfully tolerated CART with no evidence of disease or sequelae on 3-month follow-up. This is the first reported case of safe and effective delivery of cardiac BRT in BALL .

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Section: Resultsmentioning

confidence: 62%

Section: Debulking and Brtmentioning

confidence: 73%

Use of cardiac radiation therapy as bridging therapy to CAR‐T for relapsed pediatric B‐cell acute lymphoblastic leukemia

Márquez

Montiel-Esparza

Hui

et al. 2020

Pediatric Blood & Cancer

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“…Table 1 summarizes all reported cases of leukemia and lymphoma that presented pseudo-progression during CAR-T therapy. [2][3][4][5] This patient showed a rapid enlargement of EL with heat and pain after administration of CAR-T cells. Clinical course and serum interleukin-6 dominant cytokine profile (data not shown ) along with the time course of CRS indicated a pseudo-progression but not true-progression of EL.…”

mentioning

confidence: 79%

“…2,3 The changes in extramedullary lesion (EL) of relapsed or refractory ALL after CAR T-cell therapy have been recognized only in a few cases. 4,5 We report herewith pseudo-progression as an augmented immune response to the EL in a boy with relapsed infant ALL after CAR T-cell therapy.…”

mentioning

confidence: 88%

Pseudo-progressive bone lesion in a relapsed infant leukemia after chimeric antigen reseptor T-cell therapy

Yokoyama

Koga

Aasai

et al. 2021

Preprint

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“…This concept is supported by the simultaneous presence of CD19 + blasts within the anterior chamber of the left eye in complete absence of T cells while no CD19 + events could be detected within the BM or peripheral blood ( figure 1 , figure 2C, D ). CD19-CAR T cells have been previously described to infiltrate immune privileged sites beyond the CNS, documented by, for example, a recent case report on bilateral retinal detachment after CD19-CAR T-cell therapy in a patient with retinal infiltration 19 and by the efficacy of CD19-CAR T cells in testicular CD19 + leukemia. 20–22 In addition to local immune escape, mechanisms of insufficient CAR T-cell persistence may have led to relapse in our patient.…”

Section: Discussionmentioning

confidence: 99%

Leukemia escape in immune desert: intraocular relapse of pediatric pro-B-ALL during systemic control by CD19-CAR T cells

Willier¹,

Raedler²,

Blaeschke³

et al. 2020

J Immunother Cancer

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BackgroundRelapsed/refractory B-precursor acute lymphoblastic leukemia (BCP-ALL) remains a major therapeutic challenge in pediatric hematology. Chimeric antigen receptor (CAR) T cells targeting CD19 have shown remarkable initial response rates in BCP-ALL patients, while long-term leukemia control rate is only about 50%. So far, main mechanisms of BCP-ALL relapse after CD19-CAR T-cell therapy have been either insufficient CAR T-cell persistence in vivo or loss of surface CD19.Case ReportHere, we report an exceptional presentation of BCP-ALL relapse in the eye during the systemic control through CAR T-cell therapy. We report a case of fatal intraocular relapse in a pediatric patient with pro-B-ALL after initial response to CD19-CAR T-cell therapy. One month after CD19-CAR T-cell therapy, remission was documented by bone marrow aspirate analysis with absence of CD19+ cells and CD19-CAR T cells could be detected in both peripheral blood and bone marrow. At the same time, however, the patient presented with progressive visual disturbance and CD19+ cells were found within the anterior chamber of the eye. Despite local and systemic therapy, ocular relapse led to BCP-ALL dissemination and systemic relapse within weeks. The eye represents a rare site for local manifestation of BCP-ALL, but isolated intraocular relapse is a clinically unreckoned presentation of BCP-ALL in the era of CD19-CAR T cells.ConclusionDuring systemic control of BCP-ALL through CD19-CAR T cells, relapse can emerge in the eye as an immune-privileged organ. Ocular symptoms after CD19-CAR T-cell therapy should guide the clinician to elucidate the etiology in a timely fashion in order to adjust leukemia treatment strategy. Both, local immune escape as well as insufficient CAR T-cell persistence may have contributed to relapse in the reported patient. Mechanisms of relapse in an immune desert under CAR T-cell therapy require future clinical and experimental attention. In particular, ocular symptoms after CAR T-cell therapy should be considered a potentially early sign of leukemia relapse.

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Bilateral retinal detachment after chimeric antigen receptor T-cell therapy

Cited by 26 publications

References 20 publications

Use of cardiac radiation therapy as bridging therapy to CAR‐T for relapsed pediatric B‐cell acute lymphoblastic leukemia

Use of cardiac radiation therapy as bridging therapy to CAR‐T for relapsed pediatric B‐cell acute lymphoblastic leukemia

Pseudo-progressive bone lesion in a relapsed infant leukemia after chimeric antigen reseptor T-cell therapy

Leukemia escape in immune desert: intraocular relapse of pediatric pro-B-ALL during systemic control by CD19-CAR T cells

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