KTE-X19 Outcomes in Relapsed/Refractory Mantle Cell Lymphoma in ZUMA-2 Study

For the treatment of patients (pts) with relapsed/refractory (R/R) mantle cell lymphoma (MCL), the autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy known as brexucabtagene autoleucel (KTE-X19) has been licensed. ZUMA-2 revealed a 93% ORR with KTE-X19 in patients with R/R MCL (67% CR rate; median follow-up: 12.3 months; 60 efficacy-evaluable patients; Wang et al. N Engl J Med. 2020). Here, researchers published the results after an additional 2 years of observation. Leukapheresis and conditioning chemotherapy was followed by a single infusion of KTE-X19 in adult pts (18 years) with R/R MCL. As an exploratory endpoint, next-generation sequencing was used to assess minimal residual disease (MRD) in the peripheral blood (sensitivity = 10-5). All 68 of the treated patients now have updated results to provide. With a median follow-up of 35.6 months, the ORR (CR + partial response) was 91% (95% CI, 81.8-96.7), and the CR rate was 68% (95% CI, 55.2-78.5). 25 of 68 treated pts (37%) remained in ongoing response (all CR) at data cutoff, with a median DOR of 28.2 months (95% CI, 13.5-47.1). There were only three cases of late relapse > 24 months after the infusion. Median progression-free survival (PFS) was 25.8 months (95% CI, 9.6-47.6), and median overall survival (OS) was 46.6 months (95% CI, 24.9-not estimable).

About 24 of the 39 patients (pts) tested negative for MRD at month one, and fifteen of the nineteen (pts) for whom data were available at month 6. The median DOR, PFS, and OS for MRD-negative patients were not attained at the time of analysis, while these values were 6.1 months, 7.1 months, and 27.0 months, respectively, for MRD-positive patients. There was a correlation between MRD negativity at months 1, 3, and 6, with 55%, 71%, and 69% of MRD-negative pts continuing in continuous CR at data cutoff, respectively. Analysis of minimal residual disease (MRD) in circulating tumor DNA at 3 and 6 months predicted relapse with an AUC of 0.80 and 0.75, respectively. No further warning signs of danger were detected. Only 3% of treatment-emergent AEs of interest occurred between the initial and current reports. Neutropenia was the most common AE of grades 3 and 4 (7 [10%] Grade 3; 1 [1%] Grade 4). Pneumonia and an upper respiratory tract infection (n = 1) and influenza (n = 2) were the two KTE-X19-related Grade 3 serious infections that affected two patients. No other cases of cytokine release syndrome were reported. One point of significant neurologic AE, Grade 3 encephalopathy, occurred 14.0 months after the initial infusion but was deemed unrelated to the research treatment. There were three new Grade 5 AEs, but no connection to study therapy could be drawn for Salmonella bacteremia (24.9 months after infusion), myelodysplastic syndrome (25.2 months after infusion), or acute myeloid leukemia (37.5 months after information). These findings mark the most extended follow-up of any CAR T-cell therapy in patients with MCL and provide further evidence that KTE-X19 elicits long-lasting responses in R/R MCL with tolerable toxicity and a low risk of late relapse.

Source:https://meetings.asco.org/abstracts-presentations/207240

Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT02601313

Michael Wang, Javier Munoz, Andre Goy, Frederick L. Locke, Caron Alyce Jacobson, Brian T Hill, John Timmerman, Houston Holmes, Ian W. Flinn, David Bernard Miklos, John M. Pagel, Marie José Kersten, Roch Houot, Amer Beitinjaneh, Weimin Peng, Xiang Fang, Rhine Shen, Rubina Siddiqi, Ioana Kloos, Patrick Michael Reagan/Three-year follow-up of outcomes with KTE-X19 in patients with relapsed/refractory mantle cell lymphoma in ZUMA-2/J Clin Oncol 40, 2022 (suppl 16; abstr 7518) DOI10.1200/JCO.2022.40.16_suppl.7518