Therapy-related myeloid neoplasms following chimeric antigen receptor T-cell therapy for Non-Hodgkin Lymphoma

Alkhateeb, Hassan; Mohty, Razan; Greipp, Patricia T.; Bansal, Radhika; Hathcock, Matthew; Rosenthal, Allison; Murthy, Hemant S.; Kharfan‐Dabaja, Mohamed A.; Bisneto, Jose Villasboas; Bennani, N. Nora; Ansell, Stephen M.; Patnaik, Mrinal M.; Litzow, Mark R.; He, Rong; Chen, Dong; Al‐Kali, Aref; Kenderian, Saad S.; Lin, Yi; Shah, Mithun Vinod

doi:10.1038/s41408-022-00707-4

Cited by 24 publications

(17 citation statements)

References 14 publications

(20 reference statements)

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“…Although two cases of TP53 ‐mutant CH developing t‐MN after CAR‐T cell therapy were observed, it is difficult to draw definitive conclusions on causality due to limited numbers 32 . However, there are other reports of t‐MN developing after CAR‐T cell therapy in patients with CH, primarily driven by prior TP53 and PPM1D clones 34,35 …”

Section: Ch and Hematologic Malignanciesmentioning

confidence: 99%

“…32 However, there are other reports of t-MN developing after CAR-T cell therapy in patients with CH, primarily driven by prior TP53 and PPM1D clones. 34,35 Allogeneic HCT using donors with CH is associated with increased risk of chronic GVHD but a lower incidence of relapse, with no overall impact on survival. 36 In fact, among recipients with evidence of disease at the time of transplant, it may even be advantageous to use CH donors (especially DNMT3A mutant) possibly due to a higher inflammation-associated graft versus leukemia effect.…”

Section: Mosaic Chromosomal Abnormalitymentioning

confidence: 99%

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Clonal hematopoiesis of indeterminate potential and clonal cytopenias of undetermined significance: 2023 update on clinical associations and management recommendations

Mangaonkar

Patnaik

2023

American J Hematol

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Condition Overview: Clonal hematopoiesis (CH) refers to age-associated expansion of somatic variants in hematopoietic stem and progenitor cells (HSPC).Diagnosis: CH of indeterminate potential (CHIP) is operationally defined as pathogenic variants in HSPCs at a variant allele frequency ≥2%.Clinical Associations: CH is associated with increased occurrence of several hematological conditions such as cytopenias (also called clonal cytopenia of undetermined significance), hematological (predominantly myeloid but also lymphoid) neoplasms, cytosis (including monocytosis), and non-hematological conditions such as atherosclerotic cardiovascular and cerebrovascular disease, ischemic congestive heart failure, venous thromboembolism, type 2 diabetes mellitus, chronic obstructive pulmonary disease, osteoporosis, gout, with a potential protective effect in Alzheimer's disease (AD).Management Recommendations: As of now, there is limited prospective data for CH testing; however, CH detection is becoming increasingly prevalent due to ubiquitous use of somatic and germline NGS testing. This in addition to data suggesting that therapy related myeloid neoplasm (tMN) in many cases is preceded by the detection of CH clones, has led to the establishment of CH clinics at several institutions. At our institution, on a research basis, we currently recommend testing for CH for individuals with persistent (≥4 months) unexplained cytopenias, in patients with malignancies prior to adjuvant cytotoxic chemotherapy and/or radiation or radionuclide therapy, screening prior to autologous hematopoietic stem cell transplantation and chimeric antigen receptor T cell (CAR-T) therapy and to assess as to whether or not, potential germline mosaic variants actually represent CH. | INTRODUCTIONClonal hematopoiesis (CH) is defined by the detection of somatic variants in hematopoietic stem and progenitor cells, with the potential to expand over time, based on clonal selection pressures. CH was first identified by observing non-random chromosome X-inactivation patterns in the myeloid compartment of healthy women increasing with age, suggesting age-related clonal expansions, 1,2 and confirmed subsequently to be secondary to somatic TET2 mutations, laying the groundwork for future studies in CH involving large numbers of biobanked samples. 3 Interestingly, CH mutations predominantly affect the epigenetic regulator genes (most commonly; DNMT3A, TET2 and ASXL1) and also occur in myeloid neoplasms, suggesting that CH is a neoplastic precursor event, akin to monoclonal gammopathy in plasma

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Section: Ch and Hematologic Malignanciesmentioning

confidence: 99%

Section: Mosaic Chromosomal Abnormalitymentioning

confidence: 99%

Clonal hematopoiesis of indeterminate potential and clonal cytopenias of undetermined significance: 2023 update on clinical associations and management recommendations

Mangaonkar

Patnaik

2023

American J Hematol

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“…In addition, therapy-related myeloid neoplasms have been reported in 5%-10% of CAR-T cell recipients, frequently occurring within the first year after infusion and associated with a poor prognosis. 101 Although the incidence of subsequent…”

Section: Subsequent Malignanciesmentioning

confidence: 99%

“…Ongoing vigilance and monitoring of CAR‐T cell recipients is therefore required for the small but serious risk of new malignancies. In addition, therapy‐related myeloid neoplasms have been reported in 5%–10% of CAR‐T cell recipients, frequently occurring within the first year after infusion and associated with a poor prognosis 101 . Although the incidence of subsequent malignancies is anticipated to decline as CAR‐T cells move into early lines of therapy in less heavily pre‐treated populations, long‐term survivors of CAR‐T cell therapy should still have age‐appropriate cancer screening performed along with periodic monitoring of blood counts to screen for therapy‐related myeloid neoplasms.…”

Section: Subsequent Malignanciesmentioning

confidence: 99%

Long‐term survivorship care after CAR‐T cell therapy

Puckrin,

Jamani,

Jimenez‐Zepeda

2023

European J of Haematology

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While cytokine release syndrome and immune effector cell‐associated neurotoxicity syndrome are well‐recognized acute toxicities of chimeric antigen receptor (CAR) T cell therapy, these complications have become increasingly manageable by protocolized treatment algorithms incorporating the early administration of tocilizumab and corticosteroids. As CAR‐T cell therapy expands to new disease indications and the number of long‐term survivors steadily increases, there is growing recognition of the need to appropriately evaluate and manage the late effects of CAR‐T cell therapy, including late‐onset or persistent neurotoxicity, prolonged cytopenias, delayed immune reconstitution and infections, subsequent malignancies, organ dysfunction, psychological distress, and fertility implications. In this review, we provide a practical approach to the long‐term survivorship care of the CAR‐T cell recipient, with a focus on the optimal strategies to address the common and challenging late complications affecting this unique population.

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“…Among those, one out of three cases may develop myeloid neoplasms post cytotoxic therapy (MN-pCT), 2 with a characteristic shorter latency following CAR-T cells therapy (median onset time 9.1 months) compared to MN-pCT following other chemo-radiotherapies. 3 In our experience, we have faced the case of a "transient" therapy related myelodysplasia in a 45-year-old woman treated with tisagenlecleucel (tisa-cel), an autologous lentiviral-transduced 4-1BB-costimulated anti-CD19 CAR-T therapy, as the fifth line for a relapsed/refractory diffuse large B cells lymphoma evolved from low-grade lymphoma. Previous treatments included rituximab, cyclophosphamide, doxorubicin, vincristine, bendamustine, high-dose methotrexate, radiotherapy, and a Fotemustine, Etoposide, cytArabine, and Melphalan (FEAM) conditioned autologous stem cells transplantation.…”

mentioning

confidence: 99%

Spontaneous resolution of “therapy‐related myelodysplasia” occurred after treatment with CAR‐T cells: All that glitters is not gold

Frioni

Galli

Sorà

et al. 2023

Int J Lab Hematology

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Therapy-related myeloid neoplasms following chimeric antigen receptor T-cell therapy for Non-Hodgkin Lymphoma

Cited by 24 publications

References 14 publications

Clonal hematopoiesis of indeterminate potential and clonal cytopenias of undetermined significance: 2023 update on clinical associations and management recommendations

Clonal hematopoiesis of indeterminate potential and clonal cytopenias of undetermined significance: 2023 update on clinical associations and management recommendations

Long‐term survivorship care after CAR‐T cell therapy

Spontaneous resolution of “therapy‐related myelodysplasia” occurred after treatment with CAR‐T cells: All that glitters is not gold

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