Session: 622. Lymphoma Biology—Non-Genetic Studies: Poster II
Hematology Disease Topics & Pathways:
Biological Processes, immune mechanism
We therefore investigated the impact of CD47 expression on rituximab efficacy. We first studied a clinically well annotated transcriptome cohort of 939 DLBCL patients treated with either CHOP or R-CHOP, and we validated these findings in functional in vitro assays. Our analyses showed that overall survival (OS) for patients with high CD47 expression (i.e. above median) is worse compared to patients with low CD47 expression (i.e. below median) after R-CHOP (p=0.001), but not after CHOP treatment (p=0.645). Correspondingly, patients with low CD47 expression benefited most from addition of R to CHOP (HR=0.32, CI:[0.21-0.50], p<0.0001). Non--GCB patients showed a worse survival compared to GCB DLBCL patients after R-CHOP treatment (p<0.0001). Interestingly, with respect to COO classification, high expression of CD47 impacted the OS in non-GCB R-CHOP-treated patients (HR=1.9, CI:[1.14-3.26], p=0.013) but not in GCB DLBCL patients (HR=1.16, CI:[0.68-1.99], p=0.58). Importantly, high CD47 expression was found to determine the worse overall survival of non-GCB versus GCB patients (p=0.0006). No difference in OS was observed between GCB and non-GCB-patients with low CD47 expression (p=0.7662). Pro-phagocytic receptors expressed on DLBCL, i.e. SLAMF7, did not determine outcome upon R-CHOP treatment. In multivariate analysis, high CD47 expression remained significantly associated with poor survival only in non-GCB-patients.
We further investigated this differential impact of CD47 in non-GCB and GCB subtypes in vitro. Non-GCB and GCB DLBCL cell lines (n=6) were mixed with allogeneic M1 macrophages and treated with a CD47 blocking antibody, which comprises human IgG4. Results confirmed that macrophage-mediated phagocytosis by R was augmented with CD47-blocking antibody only in non-GCB DLBCL cell lines, and not in GCB DLBCL cell lines. Also, CD47 blocking co-treatment also increased the number of tumor cells ingested per macrophage, with a clear significant increase in phagocytic index in non-GCB cells, but not in GCB DLBCL cells (p=0.001).
In conclusion, the patient benefit of addition of R to CHOP is limited by CD47 specifically in non-GCB patients. In addition, we confirmed that CD47-blocking only augmented rituximab-mediated phagocytosis in non-GCB cell-lines. Together, these data suggest that especially non-GCB DLBCL patients with a currently worse prognosis may benefit from CD47-targeted therapy combined with rituximab.
Disclosures: No relevant conflicts of interest to declare.
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