CAR T-Cell Therapy Shows Highly Durable Remissions in CLL and B-Cell Lymphoma

TON - August 2020, Vol 13, No 4

According to long-term follow-up data presented at the ASCO 2020 virtual annual meeting, anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has demonstrated ongoing durable remissions lasting up to 113 months for follicular lymphoma, 99 months for chronic lymphocytic leukemia (CLL), and 97 months for diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma (PMBCL). What’s more, long-term adverse events were rare, with the exception of prolonged B-cell depletion and hypogammaglobulinemia.

“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,” said Kathryn M. Cappell, MD, PhD, Center for Cancer Research, Medical Oncology Fellowship, National Cancer Institute, Bethesda, MD.

CAR T-cell therapy that targets CD19 has been shown in multicenter clinical trials to cause complete remissions in up to 54% of patients with relapsed B-cell lymphoma, according to Dr Cappell. However, the long-term durability of these responses has not been clear.

Long-Term Data

Dr Cappell and colleagues conducted the initial study of anti-CD19 CAR T-cells with axicabtagene ciloleucel (Yescarta) that showed success in treating B-cell lymphoma and led to its approval in 2017. At ASCO 2020, the researchers presented the long-term durability of remissions and the long-term adverse effects associated with this therapy.

The study included a total of 43 patients, 3 of whom received repeated CAR T-cell infusions, for a total of 46 cell infusions. Although all the patients received conditioning chemotherapy with cyclophosphamide and fludarabine, said Dr Cappell, the cohorts differed in the dosage of conditioning chemotherapy and whether interleukin-2 was administered.

An analysis of the baseline characteristics showed that 65% of the patients had DLBCL or PMBCL, 19% had low-grade lymphoma, and 16% had CLL. In all, 49% of the patients had chemotherapy-refractory lymphoma, and an additional 19% had received autologous transplant as their last treatment before protocol enrollment.

Nearly a Decade of Response

As Dr Cappell reported, 58% of the patients had a complete response and 23% had a partial response. All the patients who remained in durable response had achieved a complete response.

“Of the 25 patients who achieved complete response with CAR T-cell infusions, 60% were evaluable and ongoing at the last follow-up appointment, and the duration of these ongoing responses ranged from 43 to 113 months,” she said.

The median event-free survival was 55 months, and the median overall survival was not reached. According to Dr Cappell, there was no difference in event-free survival or overall survival based on lymphoma type or assigned cohort. The median event-free survival for patients who achieved a complete response was not reached.

Dr Cappell and colleagues also examined the correlation of CAR T-cell levels and response; they found that patients who achieved a complete response had higher peak levels of CAR T-cells than patients who did not reach a complete response. Similarly, patients who achieved a duration of response of more than 3 years had higher peak CAR T-cell levels versus patients who did not reach this milestone. However, the persistence of the CAR T-cells was not associated with response or with duration response.

“It’s important to note that B-cell recovery did not herald lymphoma relapse,” said Dr Cappell. “Two-thirds of patients who recovered normal B-cell levels remain in ongoing complete response.”

Adverse Events

Except for B-cell depletion and hypogammaglobulinemia, long-term adverse events were rare, said Dr Cappell. She added that the only autoimmune adverse event was hypothyroidism in 1 patient.

Of the 43 study patients, 7 had a second malignancy after treatment and 4 had an infection requiring hospitalization at least 6 months after CAR T-cell therapy.

The researchers also tracked B-cell and immunoglobulin levels in the 24 evaluable patients who achieved complete response. The results showed that 9 (38%) patients never recovered a normal B-cell level, and 18 (75%) patients had a long-standing abnormality in at least 1 immunoglobulin.

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