CAR-based Cellular Therapy: clinical ePoster

A116 - CAR-T IN BREAST AND OTHER EXTRA-MEDULLARY RELAPSED/REFRACTORY ALL (ID 1027)

Authors
  • F. Tambaro
  • S. Khazal
  • D. Ragoonanan
  • P. Tewari
  • D. Petropolous
  • J. Miller
  • W. Wierda
  • R. Champlin
  • K. Mahadeo

Abstract

Background:
Extra-medullary ALL develops in sanctuaries including, CNS, genitourinary and “sequestered sites” (gut, breast, skin). Data regarding complete remission (CR) rates and durability of response among patients receiving CART with relapsed/refractory (r/r) ALL and extra-medullary disease is still emerging.

Methods:
We report two AYA patients with r/r ALL and extra-medullary involvement who achieved CR after tisagenlecleucel.

Results:
Patient 1 was refractory to 7 prior lines of therapy and developed CNS, liver, spleen and bilateral kidney involvement; He experienced CD19 negative relapse approximately 8 weeks later. He subsequently achieved CR following two doses of inotuzumab and then received a reduced intensity (RIC) related haplo-identical SCT. He experienced a CNS relapse approximately 2 months later and died shortly after. Patient 2 had isolated bilateral breast involvement following allogeneic stem cell transplantation (SCT). She experienced swelling and erythema of the breast tissue following CART and achieved MRD negative CR in the bone marrow with partial response in the breast. She subsequently received XRT to the breast and was consolidated with a RIC SCT. She died approximately 100 days post-SCT from sepsis.

Conclusions:
The majority of 53 reported patients with ALL and extra-medullary breast involvement (22 occurred post-SCT) received combined radiation and chemotherapy; 4 received DLI and achieved CR but 2 died of severe GvHD. CAR-T cells, may likewise circulate and act in sequestered sites but without GvHD. Lympho-depletion preceding CAR-T may also eliminate regulatory T lymphocytes and potentially enhance the immune response. Combined treatment with CAR-T and radiation may help eradicate extra-medullary disease, taking advantage of the local death of dividing cells with radiation with potential enhancement of the microenvironment to facilitate CAR-T function and enhance anti-tumor immune response of resident T cells. Future studies will elucidate the optimal timing of CART among patients with extra-medullary disease, which may improve durability of response and long-term outcomes.

Disclosure:
Nothing to declare

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