Long-term follow-up shows that the CAR-T cell therapy Tecartus continues to elicit durable responses in patients with relapsed/refractory mantle cell lymphoma.
Long-term follow up from the phase 2 ZUMA-2 clinical trial showed that treatment with Tecartus (brexucabtagene autoleucel) continues to benefit patients with relapsed or refractory mantle cell lymphoma (MCL), with nearly all patients responding to the CAR-T cell therapy.
Earlier findings from ZUMA-2 led to the Food and Drug Administration’s 2020 approval of Tecartus for MCL, marking the first CAR-T cell therapy to become available in this space.
At a median follow-up of 35.6 months, the objective response rate (which measures the percentage of patients whose disease shrunk as a result of treatment) was 91% among the 68 treated patients, of whom 68% had a complete response, meaning that there was no detectable cancer left, and 24% had a partial response, where the disease decreased, but was still detectable.
On average, responses lasted 28.2 months, with a median progression-free survival (time from treatment until disease worsens) of 25.8 months, and a median overall survival (time from treatment until death of any cause) of 46.6 months.
As previously reported, total of 74 patients enrolled and underwent a process called leukapheresis to take out white blood cells, 68 of whom received full treatment. In the updated analysis, after initial stable disease or partial response, 25 patients converted to a complete response, with the median time to response conversion of 2.3 months.
At the time the study data was collected, the median duration of response was 46.7 months for patients who had a complete response (46 patients) and 2.2 months for patients with a partial response (16 patients). Of the first 28 patients treated, the median follow-up was 51.1 months; the median duration of response was 36.5 months in 26 responders and 29% had an ongoing response.
For patients whose best response was complete response, the median progression-free survival was 48 months. For those with a partial response, the median progression-free survival was 3.1 months and 2.3 months with no response.
At the post-infusion week four visit, 94% of patients experienced their disease shrinking from treatment, which was followed by a landmark analysis assessing progression-free survival by response type. The median progression-free survival for those whose best response was a complete response was 46.7 months, 13.6 months for a partial response and 11 months with no response.
An analysis showed that patients who had a complete response were less likely to experience disease relapse than those who had a partial or lack of response.
The median overall survival in patients whose best response was a complete response was not reached as so many patients were still alive at the point of data collection, and was 16.3 months for partial response and 8.5 months for no response.
Minimal residual disease (MRD) was assessed in 19 patients at six months, of whom 79% were MRD-negative (meaning that there were no remains of cancer left behind after treatment) with an overall response rate of 100%.
Of those who were MRD-positive (those who had some disease left behind), two achieved a complete response, one achieved a partial response and one had progressive disease. Additionally, in the MRD-positive population, the median duration of response was 6.1 months, median progression-free survival was 7.1 months, and median overall survival was 27 months.
For those who were MRD-negative, the median duration of response, progression-free survival and overall survival were not reached at data cut-off, and 60% had an ongoing response.
Of those in the intent-to-treat population, the overall response rate was 84%, including a 62% complete response rate and a 22% partial response rate. The median progression-free survival was 24 months and the 24-month progression-free survival rate was 49%. Moreover, the median overall survival in this population was 47.4 months, with a 24-month overall survival rate of 56%.
Investigators did not observe any new safety signals during longer follow-up, with 3% of all treatment-emergent side effects occurring since the previous data report.
The most frequent grade 3 or higher (serious, severe or fatal) side effect was neutropenia (when the body produces too few white blood cells) with 1% of patients having grade 3 and 10% having grade 4 events. Grade 3 or higher serious side effects were reported in 10% of patients, with one patient having grade 3 encephalopathy (a disease that alters brain function or structure) that was not related to treatment. Two patients had serious side effects related to treatment, including one with grade 3 pneumonia and grade 3 upper respiratory tract infection, and one with grade 3 influenza.
A total of three patients experienced fatal side effects which included salmonella bacteremia (when salmonella infection enters into the bloodstream) beginning at 24.9 months, myelodysplastic syndrome (a group of cancers in which immature blood cells in the bone marrow do not mature or become healthy blood cells) occurring at 25.2 months and acute myeloid leukemia occurring at 37.5 months.
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