Anti-CD22 and anti-CD79B antibody drug conjugates are active in different molecular diffuse large B-cell lymphoma subtypes

Abstract

Antibody drug conjugates (ADCs), in which cytotoxic drugs are linked to antibodies targeting antigens on tumor cells, represent promising novel agents for the treatment of malignant lymphomas. Pinatuzumab vedotin is an anti-CD22 ADC and polatuzumab vedotin an anti-CD79B ADC that are both linked to the microtubule-disrupting agent monomethyl auristatin E (MMAE). In the present study, we analyzed the activity of these agents in different molecular subtypes of diffuse large B-cell lymphoma (DLBCL) both in vitro and in early clinical trials. Both anti-CD22-MMAE and anti-CD79B-MMAE were highly active and induced cell death in the vast majority of activated B-cell-like (ABC) and germinal center B-cell-like (GCB) DLBCL cell lines. Similarly, both agents induced cytotoxicity in models with and without mutations in the signaling molecule CD79B. In line with these observations, relapsed and refractory DLBCL patients of both subtypes responded to these agents. Importantly, a strong correlation between CD22 and CD79B expression in vitro and in vivo was not detectable, indicating that patients should not be excluded from anti-CD22-MMAE or anti-CD79B-MMAE treatment because of low target expression. In summary, these studies suggest that pinatuzumab vedotin and polatuzumab vedotin are active agents for the treatment of patients with different subtypes of DLBCL.

The current role of clinical flow cytometry in the evaluation of mature B‐cell neoplasms

“…Potential therapeutic options include monoclonal antibodies directed against the B-cell associated antigens CD20, CD22, and CD79 (59), antibody drug conjugates (ADC), such as anti-CD22 and anti-CD79b ADC microtubule-disrupting agent monomethyl auristatin E (MMAE) (60) and anti-CD19 chimeric antigen receptor-modified T (CAR-T) cells (61). In addition, ADCs appear less dependent on the level of target antigen, with responses demonstrated at low levels of antigen expression that may not be detectable using less sensitive immunohistochemical methods (60). In addition, ADCs appear less dependent on the level of target antigen, with responses demonstrated at low levels of antigen expression that may not be detectable using less sensitive immunohistochemical methods (60).…”

Diffuse Large B Cell Lymphoma Cell Line U-2946: Model for MCL1 Inhibitor Testing

“…The majority of ten ABC and GC markers described by Ruminy et al [33] class U-2946 as ABC DLBCL cell line. B) Applying the same set of marker genes, cell line U-2946 clustered together with described ABC DLBCL cell lines (red), not with GC cell lines (green) [5–9]. Cell line NU-DHL-1 (orange) was discordantly categorized by different authors [6,8].…”

“…Expression array analysis has identified two molecularly distinct forms of the tumor, termed germinal center (GC) and activated B-cell (ABC) [4]. DLBCL-derived cell lines also show correspondingly distinct expression profiles allowing classification according to the GC- and ABC-scheme [5–9]. In contrast to GC-type DLBCL, ABC-type cells rely on the constitutive activation of the NF-kB pathway to block apoptosis [10].…”

High‐dose cyclophosphamide for hard‐to‐treat patients with relapsed or refractory B‐cell non‐Hodgkin's lymphoma, a phase II result

“…This leads to consider high‐dose cyclophosphamide as a waiting treatment before another treatment such as CAR‐T cell or waiting for the patient to enter a clinical trial with a new drug. In the setting of relapse or refractory non‐Hodgkin B‐cell lymphoma, some new therapies are now available beyond two lines of treatments such as cellular therapies with chimeric antigen receptor (CAR)‐T cells, bi‐specific T‐cell engager, or immunoconjugates anti‐CD22 or CD79B agents . The impressive response rates of 82%, including 54% of complete responses with CAR‐T cells axicabtagene ciloleucel, are profoundly changing the treatment landscape of relapse or refractory DLBCL.…”