The following article features coverage from the American Society of Hematology 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

The expression of target antigen CD19 on B cells was lower in tumor biopsies from patients with large B-cell lymphoma (LBCL) whose disease relapsed after treatment with axicabtagene ciloleucel (axi-cel), offering a potential explanation for treatment resistance. During the presentation, the researchers noted that loss of CD19 expression was common at relapse post–axi-cel. The study findings were presented at the 61st American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, Florida.1

The tumor biopsies included in the analysis were from patients enrolled in cohorts 1 and 2 of ZUMA-1. Results of ZUMA-1 previously showed that approximately 60% of patients relapse or progress after axi-cel. Overall, in the current study, 82 patients had tumor samples available for immunohistochemistry (IHC) analysis before treatment, and 18 patients had tumor samples available for IHC after disease relapse.

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According to the live presentation, for 16 patients, both the before treatment and after disease relapse samples were available. Loss of CD19 occurred in 4 of 16 of these patients.

A post-hoc analysis was done to evaluate protein expression of CD19 as well as other B-cell lineage markers, including CD20, PAX5, CD79a, and CD22, in the tumor samples.

Approximately one-third of tumor samples after disease relapse had a loss of CD19 expression. Among the patients with paired samples, approximately 25% (4 of 16) of patients also had loss of CD19 expression.  

The other B-cell lineage markers — that is, CD20, PAX5, CD79a, and CD22 — remained expressed, including in samples that had CD19 loss. This was observed across 18 tumor samples at relapse. Among the samples that were evaluable by IHC, 72% still expressed CD19, 94% had CD22 expression, and 100% of those samples had CD20, CD79a, and PAX5 expression.

“Antigen escape post–axi-cel may be mediated by selection of tumor cells with lower CD19 expression, or of tumor cells expressing alternate CD19 splicing variants,” the researchers noted. The alternative splicing events at baseline and relapse were significantly different (P <.05). These splicing events likely led to the loss of the CAR-binding epitope.

All the patients included in the analysis had previously relapsed while being administered rituximab. Despite rituximab targeting CD20, the antigen was “robustly” expressed in “nearly all” samples before treatment with axi-cel.

“Altogether, these data point to strategies to improve efficacy of anti-CD19 CAR T-cell products through co-targeting or sequential targeting of alternate B-cell antigens,” the study authors wrote concluded.

Disclosure: Some of the authors disclosed financial relationships with the pharmaceutical industry. For a full list of disclosures, please refer to the original abstract.

Read more of Cancer Therapy Advisor‘s coverage of ASH’s annual meeting by visiting the conference page.

Reference

Neelapu SS, Rossi JM, Jacobson CA, et al. CD19-loss with preservation of other B cell lineage features in patients with large B cell lymphoma who relapsed post–axi-cel. Presented at: 61st American Society of Hematology (ASH) Annual Meeting and Exposition; December 7-10, 2019: Orlando, Florida. Abstract 203.