Poster Presentation Melbourne Immunotherapy Spring Symposium 2025

Circulating tumour DNA-directed consolidation with epcoritamab alone or in combination with lenalidomide and rituximab is feasible in the early post-CAR-T population at high risk of relapse: preliminary results from EpLCART (#136)

Mark R Dowling 1 2 3 , Shafqat Inam 4 , Hamish Scott 1 , Jian Li 4 , LeiShong Lau 1 , Sam van der Linde 1 , Nicole O'Leary 1 , Irene Lee 3 , Gaurav Sutrave 5 , Sushmitha Kannan 6 , Sally Hunter 6 , Ella Thompson 6 , Jane Oliaro 2 3 , Mohammad Atiya 7 , Charles Kearns 8 , Constantine Tam 4 9 , Emily Blyth 5 10 11 , Piers Blombery 2 6 , Michael Dickinson 1 2
  1. Clinical Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital,, Melbourne, Victoria, Australia
  2. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia
  3. Centre of Excellence for Cellular Immunotherapy, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
  4. Malignant Haematology Transplantation and Cellular Therapy Service, Alfred Hospital, Melbourne, Victoria, Australia
  5. Blood Transplant and Cell Therapies Program, Westmead Hospital, Sydney, New South Wales, Australia
  6. Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
  7. Genmab US, Plainsboro, New Jersey, United States of America
  8. Abbvie Inc, North Chicago, Illinois, United States of America
  9. Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria, Australia
  10. Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
  11. Westmead Institute for Medical Research, Sydney, New South Wales, Australia

Introduction:  Half or more patients treated with anti-CD19 chimeric antigen receptor (CAR) T-cell therapy for relapsed and/or refractory (R/R) large B-cell lymphoma (LBCL) do not experience durable remissions. Patients that have responded to CAR-T by conventional radiologic criteria but with detectable ctDNA (minimal residual disease [MRD] positive) are at high risk of subsequent progression. We hypothesised that CD20xCD3 bispecific antibodies (BsAb) may prevent progression in MRD positive patients, and that a low-burden disease state may lead to favourable disease control and safety profile from a fixed course of BsAb. Here we report preliminary results up to the interim response assessment after Cycle 2 for the first 10 patients enrolled in EpLCART (NCT06414148)

Methods: Eligible patients must have received commercial CAR-T for LBCL and be in a response by PET but MRD positive between D+25 and D+100 post-infusion. ctDNA MRD status is reported using the KAPA HyperCap DS NHL panel (Roche Diagnostics) and a a custom bioinformatics pipeline, based on reporter variants establish from baseline tumour or ctDNA. Enrolled patients receive 6 cycles of epcor-alone or epcor-R2.

Results: 42 patients underwent ctDNA testing after CAR T-cell infusion between February 5, 2024, and November 4, 2024. The median turn-around time was 12 days. 14 patients (33%) were MRD positive between D+25 and D+100 post infusion, and 10 patients enrolled in EpLCART. The treatment was well-tolerated, with no cases of Grade >1 CRS and no ICANS. There were 9 clinical or microbiologically proven infections. At the interim response assessment, 8 out of 10 patients were MRD negative.

Conclusions: Monitoring of ctDNA after CAR T-cell infusion is feasible, with a turn-around time that allows intervention prior to clinical progression in most cases to date.  Epcor-alone or Epcor-R2 appears deliverable in the early post-CAR-T period, with a favourable toxicity profile and encouraging MRD responses.