The following article features coverage from the American Society of Clinical Oncology 2020 meeting. Click here to read more of Hematology Advisor’s conference coverage.

 

Long-term follow-up of the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in patients with B-cell lymphoma and chronic lymphocytic leukemia (CLL) demonstrated highly durable remissions with few long-term adverse effects. These findings were presented by Kathryn Cappell, MD, PhD, of the National Cancer Institute, during the ASCO20 Virtual Scientific Program.

Between 2009 and 2015, the investigators conducted the first clinical trial (ClinicalTrials.gov Identifier: NCT00924326) of anti-CD19 CAR T cells that showed responses against lymphoma. The CAR from that trial, FMC63-28Z, was subsequently developed as axicabtagene ciloleucel.

In the original study, 43 patients were treated with anti-CD19 CAR T cells (46 total infusion as 3 patients were retreated) following conditioning chemotherapy of cyclophosphamide plus fludarabine. Most (28 patients) had aggressive lymphoma (diffuse large B-cell lymphoma or primary mediastinal B-cell lymphoma), while the rest had low-grade lymphoma (5 patients with follicular lymphoma, 1 patient with splenic marginal zone lymphoma, 1 patient with mantle cell lymphoma, and 1 patient with unspecified low-grade non-Hodgkin lymphoma) or CLL (7 patients).

The patients had a median age of 54 years (range, 24-68 years), and most (77%) were male. At baseline, 49% had chemotherapy-refractory disease, and the median number of previous lines of therapy was 4 (range, 1-12). Patients had received a median CAR+ T cell dose of 2´106 per kilogram.


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With long-term follow-up, the overall remission rate was 81%. Best response of complete remisson (CR) and partial remission (PR) occurred in 25 (58%) and 10 (23%) patients, respectively. Patients who achieved a best response of PR or stable disease did not have durable responses. Of the 25 CRs, 15 (60%) were still evaluable and ongoing at the last follow-up appointment. The duration of response (DOR) for these ongoing CRs ranged from 43 to 113 months.

For the 45 evaulable treatments, the median event-free survival was 55 months and did not differ among disease type. The median overall survival and the median overall survival for patients who reached CR was not reached.

The investigators also assessed the association between peak blood CAR+ cell levels and response and duration of response. The median peak blood CAR+ cell levels in patients with CR was was higher (86 CAR+ cells/uL) than those who did not achieve CR (16 CAR+ cells/uL; P =.0041). Similarly, the median peak blood CAR+ cell levels in patients with a DOR of more than 3 years was higher (98 CAR+ cells/uL) than those with a DOR of less than 3 years (18 CAR+ cells/uL; P =.0051).

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Long-term adverse effects were rare. Notable exceptions were B-cell depletion and hypogammaglobulinemia; among 24 evaluable patients who achieved CR, these both improved over time. However, 9 patients (38%) did not recover normal B-cell levels, but that authors noted that B-cell recovery was observed without relapse. Most of these patients (18/24; 75%) had persistent low levels of at least 1 immunoglobulin.

“These are the longest reported responses in B-cell lymphoma,” said Dr Cappell. “Overall, the very durable responses seen in our study raise the possibility, but do not prove, that anti-CD19 CAR T cells may be curative for some types of B-cell lymphoma.”

Reference

Cappell K, Sherry RM, Yan JC, et al. Long-term follow-up of anti-CD19 CAR T-cell therapy for B-cell lymphoma and chronic lymphocytic leukemia. Presented at: ASCO20 Virtual Scientific Program. J Clin Oncol. 2020;38(suppl):abstr 3012.