PI3Kδ activation, IL6 over-expression, and CD37 loss cause resistance to the targeting of CD37-positive lymphomas with the antibody-drug conjugate naratuximab emtansine.
Alberto J ArribasEugenio GaudioSara NapoliCharles Jean Yvon HerbauxChiara TarantelliRoberta Pittau BordoneLuciano CascioneNicolas MunzLuca AresuJacopo SgrignaniAndrea RinaldiIvo KweeDavide RossiAndrea CavalliEmanuele ZuccaGeorg StussiAnastasios StathisCallum SlossMatthew S DavidsFrancesco BertoniPublished in: bioRxiv : the preprint server for biology (2023)
evidence of anti-tumor activity in lymphoma and chronic lymphocytic leukemia (CLL) (7,10), naratuximab emtansine entered the clinical evaluation as a single agent. The phase 1 study exploring naratuximab emtansine enrolled 39 patients with relapsed/refractory B cell lymphoma (27). The overall response rate (ORR) was 13% across all patients and 22% in DLBCL patients, including the only observed complete remission (CR) (27). In preliminary results of a phase 2 trial exploring the combination of naratuximab emtansine with the anti-CD20 monoclonal antibody rituximab (18), based on positive preclinical data (18), the ORR was 45% in 76 patients with DLBCL with 24 CRs (32%), 57% in 14 patients with follicular lymphoma (five CR), 50% in four MCL patients (2 CR) (31). Here, we studied the pattern of activity of naratuximab emtansine across a large panel of cell lines derived from DLBCL and other lymphoma subtypes and characterized two resistance mechanisms to the ADC.
Keyphrases
- diffuse large b cell lymphoma
- end stage renal disease
- newly diagnosed
- ejection fraction
- chronic kidney disease
- peritoneal dialysis
- positive breast cancer
- randomized controlled trial
- monoclonal antibody
- clinical trial
- stem cells
- machine learning
- metastatic breast cancer
- rheumatoid arthritis
- magnetic resonance
- magnetic resonance imaging
- poor prognosis
- bone marrow
- mesenchymal stem cells
- open label
- patient reported
- systemic lupus erythematosus
- study protocol
- binding protein
- diffusion weighted