CAR-T Therapy Targeting CD19 and CD20 Demonstrates High Responses in MCL
Results from a phase 1/2 trial investigating LV20.19 found that the CAR-T therapy was safe and effective in 11 patients with R/R MCL, with an ORR of 100% and no relapses seen after a median follow up of more than 1.5 years.3
“Our group has previously published data using a bispecific tandem anti-CD20 and anti-CD19 CAR T-cell construct as part of a phase 1 clinical trial where we identified a cell dose of 2.5×106 cells/kg to be the safe dose for future investigation…with durable responses 4 years out,” study presenter Nirav N. Shah, MD, an associate professor with the Medical College of Wisconsin in Milwaukee, Wisconsin, said.
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Eligible patients for this study must have failed 2 lines of therapy or relapsed after autologous or allogeneic HSCT. There was a dedicated arm of the study for patients with MCL in a single-stage phase 2 design, with the 3-month CR rate as the primary target endpoint.
There were 3 patients who were included in the safety run-in portion of the trial and 11 included in phase 2. The median age was 63 years and 93% of participants were male. Additionally, 93% of patients had received prior BTK inhibitor treatment and 79% had progressed after BTK inhibitor therapy.
At day 28, the ORR was 100%, with 71% being CRs and the investigators seeing evolution over time. At day 90, the ORR was 100% in the surviving 12 patients, 92% as CRs. The median PFS and OS were not met after nearly 2 years of follow up, with durable responses and only 1 relapse seen at 2 years postinfusion.
In terms of safety, 1 patient had nonrelapsed mortality due to gram-negative sepsis, although they were negative for minimal residual disease at the time. There were 2 grade 3 cases of immune effector cell-associated neurotoxicity syndrome. Of the 14 patients included, 13 experienced grade 1 to 2 cytokine release syndrome. No patients required admission to the intensive care unit during the first 28 days of the trial.
“In conclusion, bispecific LV20.19 CAR T-cells are safe and efficacious for multiply-relapsed and refractory mantle cell lymphoma with a day 90 CR rate of 92% among evaluable patients,” said Dr Shah. “These data hypothesize that the dual targeting of CD20, which is an important target in mantle cell lymphoma outside of CAR-T, may be additive to CD19 and improve CAR-T therapy outcomes for patients with relapsed or refractory mantle cell lymphoma.”
A multicenter phase 2 trial is presently under development to validate these findings.
Disclosures: The MAGNOLIA study was sponsored by BeiGene and the TRANSFORM trial was sponsored by Celgene, a Bristol-Myers Squibb Company. Please see the original references for a full list of authors’ disclosures.
References
- Opat S, Tedeschi A, Hu B, et al. Long-term efficacy and safety of zanubrutinib in patients with relapsed/refractory (R/R) marginal zone lymphoma (MZL): final analysis of the Magnolia (BGB-3111-214) trial. Presented at: 2023 Tandem Transplantation and Cellular Therapy Meetings of ASTCT and CIBMTR. Abstract 132.
- Abramson JS, Solomon SR, Arnason J, et al. Primary analysis results from the randomized, phase 3 transform study of lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma. Presented at: 2023 Tandem Transplantation and Cellular Therapy Meetings of ASTCT and CIBMTR. Abstract 44.
- Shah NN, Furqan F, Szabo A, et al. Results from a phase 1/2 study of tandem, bispecific anti-CD20/anti-CD19 (LV20.19) CAR T-cells for mantle cell lymphoma. Presented at: 2023 Tandem Transplantation and Cellular Therapy Meetings of ASTCT and CIBMTR. Abstract 40.
This article originally appeared on Hematology Advisor
