Dual CD19- and CD20-targeting CAR T-cell therapy was effective and had a unique safety profile in patients with relapsed/refractory CLL.
The CD19- and CD20-targeting CAR (chimeric antigen receptor) T-cell therapy LV20.19 generated a high complete response (CR) rate in patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL), according to data from a phase 1/2 trial (NCT04186520) presented at the
Results from the trial showed that, at a median follow-up of 25 months, 78% of patients with R/R CLL who received LV20.19 (n = 18) achieved a CR or CR with incomplete bone marrow recovery (CRi). Additionally, 11% of patients achieved a partial response, 6% had stable disease, and 6% were not evaluable for response.
Patients in the trial achieved a median progression-free survival (PFS) of 32 months and a 24-month overall survival rate of 79%. Moreover, 24% of patients relapsed, whereas 7 patients reached minimal residual disease negativity from days 30 to 90 of treatment.
LV20.19 in Relapsed/Refractory CLL: Take-Home Points
“Bispecific LV20.19 CAR T cells demonstrated exciting overall response/CR [rates] in patients with relapsed/refractory CLL but with a different toxicity profile than seen in other B-cell malignancies,” lead study author Nirav N. Shah, MD, said in a presentation of the data. “Dual targeting of CD20 in addition to CD19 may improve CAR T-cell therapy outcomes for CLL, with a median PFS of 32 months.”
Shah is an associate professor of medicine in the Division of Hematology and Oncology and the clinical director of bone marrow transplantation and cellular therapy at the Medical College of Wisconsin in Milwaukee.
Investigators of the trial sought to improve outcomes of a previous trial that evaluated LV20.19 in patients with CLL. The current trial used a shortened CAR T-cell manufacturing process and higher-potency cytokines to enhance the functionality, persistence, and expansion of LV20.19.
The study enrolled patients aged 18 to 80 years with R/R CLL.1,2 Patients had to have received 2 prior lines of therapy, 1 of which had to be either Bruton tyrosine kinase (BTK) or BCL-2 inhibition. A Karnofsky performance score of 70 or higher, adequate hepatic function, and an absolute cluster differentiation 3 count of 50 mm3 or higher were also required for enrollment.
If patients had confirmed hepatitis B, hepatitis C, or HIV; significant autoimmune disease; or received previous CD19- or CD20-targeting CAR T-cell therapy within 100 days of enrollment, they were not included in the trial.
Patients in the trial received a fixed LV20.19 dose of 2.5 x 106 cells/kg on a flexible 8- to 12-day schedule. Notably, patients were administered a lymphodepletion regimen consisting of 30 mg/m2 of fludarabine and 300 mg/m2 of cyclophosphamide once daily starting 4 days before receiving LV20.19.1 Patients then underwent monitoring for at least 28 days after receiving LV20.19 infusions.1,2
The primary end point of the trial is to determine the incidence of adverse effects following CAR T-cell therapy infusion.2
Baseline characteristics revealed that patients had a median age of 65 years (range, 34-75) and were mostly male (83%).1 Most patients were either BTK or BCL-2 inhibitor refractory (83%), and less than half of patients had ATM/11q abnormalities (44%). Complex cytogenetics and p53 aberrations were present in 56% and 33% of patients, respectively. Ninety-four percent of patients received a fresh infusion and used an 8-day manufacturing length; 1 patient used a 12-day manufacturing length. Patients had received a median of 4 prior lines of therapy (range, 2-7). Ten patients received an LV20.19 dose of 2.5 x 106 cells/kg compared with 8 patients who received a dose of 1.0 x 106 cells/kg.
Any-grade cytokine release syndrome (CRS) occurred in 94% of patients; 89% had grade 1/2 CRS, and 5% had grade 3/4 CRS. Furthermore, any-grade immune effector cell–associated neurotoxicity syndrome (ICANS) was experienced by 22% of patients; grade 1/2 and grade 3/4 ICANS each occurred in 11% of patients. Half of patients experienced immune effector cell–associated hemophagocytic lymphohistiocytosis–like syndrome (IEC-HS); 44% of patients experienced grade 1/2 IEC-HS, and 6% of patients experienced grade 3/4 IEC-HS. Notably, IEC-HS was not reported at the same frequency in patients with other disease histologies.
Two dose-limiting toxicities were seen in patients with grade 3 ICANS and grade 4 IEC-HS, who both received LV20.19 at 2.5 x 106 cells/kg. Patients had a mean ferritin level of 31,194 ng/mL with IEC-HS and 1162 ng/mL without IEC-HS. Tocilizumab (Actemra), steroids, and anakinra (Kineret) were administered in 89%, 61%, and 39% of patients, respectively.
“In this multicohort clinical trial, the rates of IEC-HS were highest in patients with CLL followed by [patients with] mantle cell lymphoma, both diseases that often have a larger circulating component,” Shah added.
Disclosures: Shah reported participating in advisory boards as an advisor for AbbVie, AstraZeneca, BeONE, BMS-Juno, Genentech, Gilead-Kite, Incyte, Janssen, LOXO-Lilly, Nurix, and Seattle Genetics; receiving research funding as a researcher from Genentech, LOXO-Lilly Oncology, and Miltenyi Biotec; participating as a consultant for Incyte, Lilly Oncology, and Miltenyi Biotec; and participating on the scientific advisory board as a member/founder for Tundra Therapeutics.
