Centre Hospitalier Universitaire de Rouen

The aim of this study is to determine whether chemotherapy prior to tumor removal (neoadjuvant chemotherapy), in patients undergoing treatment for colon cancer in occlusion (CCO), would improve the rate of patients able to benefit from "optimal" treatment, i.e. complete treatment (including all neoadjuvant and adjuvant chemotherapy cures).
This new strategy, which would combine chemotherapy before surgery and possibly post-operatively (depending on tumor analysis), could improve the prognosis of occluded colon cancers by treating circulating micrometastases and/or inducing a reduction in tumor size, thereby increasing the rate of complete resection.

Refractory/Relapsed (R/R) acute myeloid leukemia (AML) is associated with a dis-mal prognosis.
In some subsets of AML such as AML driven by the t(8;21) translocation, leading to the RUNX1-RUNX1T1 (AML1-ETO) fusion transcript expression, CD19 B-cell antigen is aberrantly expressed on malignant blasts in around 80 % of cases. Interestingly, the expression of the CD19 antigen is also detected in the CD34+ CD38-population leukemic stem cells.
t(8;21) AML subtype has a rather good prognosis with an intensive chemotherapy regimen, but relapses occur in around 40 % of the patients and new therapeutic options are needed for these patients.
Plesa et al, reported a successful treatment of a refractory t(8;21) AML with bispecific monoclonal antibodies that targets CD19. More recently, Danylesko et al, have reported long-term remission following CD19 CAR-T cells in a heavily pre-treated patient with t(8;21) AML(1). The same group has just submitted an abstract of 6 treated patients to the European Haematology Association (EHA) 2023 meet-ing: Six patients (adults-5, child-1) with t(8; 21) AML (confirmed by cytogenetic and FISH) and aberrant CD19 expression were included. One patient had a complex karyotype. Molecular analysis for CKIT, NPM1, IDH1, IDH2, and CBPa were nega-tive in all pts. One pt harbors the FLT3 ITD and TKD mutations. Median number of previous chemotherapy (CT) lines was 4 (3-8). Four patients were with chemo re-sistant relapse post allo-HCT (MSD-1, 10/10 MUD -3) 5-18 months before CAR T-cell infusion. All patients developed CRS (grade 1-3) and were treated with i.v tocili-zumab and dexamethasone. 2/6 patients suffered from ICANS and were treated with steroids. In 4/6 patients, day 28 BM aspiration disclosed normal hematopoie-sis with no excess blasts and lack of t(8;21) by FISH confirming clinical and cyto-genetic remission, while 2/6 pts with progressive AML had no response (Danylesko etal. Abstract EHA 2023, submitted).
Interestingly, other subsets of AML display an aberrant expression of CD19. These observations indicate that CD19 can be a target of choice for CAR-T cells in patients with R/R AML expressing this antigen.
In this study, we plan to offer anti-CD19 CAR-T cell therapy to patients with re-lapsed/refractory AML expressing CD19 for whom no curative alternatives are available.
To this end, CAR-T cells will be manufactured using closed semi-automated bioreactor CliniMACS Prodigy (Miltenyi Biotec) in academic setting.

Bevacizumab is a standard drug for metastatic colorectal cancer (mCRC) in combination with cytotoxic chemotherapy. However, inter-individual pharmacokinetic variability was observed for bevacizumab and an exposure-response relationship for efficacy was described for bevacizumab in mCRC patients treated with 1st-line bevacizumab-based chemotherapy.