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Third Generation CAR T Product Shows Efficacy in Follicular Lymphoma

Further data from Mustang Bio’s phase 1/2 trial will be presented at the EHA 2022 Congress.

The CD-20-targeted chimeric antigen receptor (CAR) T-cell receptor therapy MB-106 has yielded efficacy in patients with follicular lymphoma (FL).1

Data from Mustang Bio’s phase 1/2 clinical trial (NCT03277729) enrolling patients with relapsed or refractory B-cell non-Hodgkin lymphomas (-NHL) and chronic lymphocytic leukemia (CLL)demonstrated that the therapy was well-tolerated with high overall objective response rates (ORR) and complete response (CR) rates in this population. Further data from the FL cohort of the trial will be presented by Mazyar Shadman, MD, MPH, associate professor and physician, Fred Hutchinson Cancer Center, at the European Hematology Association 2022 Hybrid Congress, June 9-12, 2022.

"...We are encouraged by the enthusiasm of these investigators for the durability of the responses and for the expansion of enrollment at Fred Hutch from CAR T naïve follicular lymphoma patients to patients previously treated with CAR Ts and to patients with other CD20-positive histologies such as diffuse large B cell lymphoma, Waldenstrom macroglobulinemia and CLL. Finally, as Mustang continues to advance our CD20-targeted CAR T cell therapy program, we look forward to the planned dosing of the first patient in a multicenter Phase 1/2 clinical trial evaluating the safety and efficacy of MB-106 for relapsed or refractory B-NHL and CLL under Mustang’s IND this quarter.” Manuel Litchman, MD, president and chief executive Officer, Mustang Bio, said in a statement.2

Sixteen patients with FL have been treated with MB-106 as of the cutoff date of December 2021. These patients had a median age of 61.5 years (range, 45-81) and were dosed at 4 dose levels of 3.3x105 (n = 1), 1x106 (n = 4), 3.3x106 (n = 7), and 1x107 CAR T cells/kg (n = 2) after lymphodepletion with cyclophosphamide with or without fludarabine.

Enrolled patients had high-risk features such as progression of disease within 24 months of first-line chemotherapy (n=11; 69%), history of histologic transformation (n=3; 19%), prior treatment with a CD19 targeted CAR-T (n=1; 6%), and presence of PI3 kinase inhibitor (n = 6; 37.5%). The median time between leukapheresis and lymphodepletion was 15 days (range, 9-21) and 2 patients received bridging therapy with lenalidomide or high-dose corticosteroids.

Overall response (ORR) rate was 94% (15/16) and complete response (CR) rate was 75% (12/16). Patients who received DL3 or DL4 had an ORR of 100% and CR rate of 89%. One patient that was previously treated with a CD19 targeted CAR-T therapy achieved a CR. Patients were followed up for a median of 10 months. One patient died from complications from myelodysplastic syndrome. Most remissions have continued, with 4 patients relapsing a median of 7 months after treatment. At follow-up of up to 2 years, 15 of 16 patients had undetectable CAR T-cells by flow cytometry.

Investigators observed no dose-limiting toxicities or immune effector cell-associated neurotoxicity syndrome and instances of cytokine release syndrome were grade 1 (n = 4; 25%) or grade 2 (n = 1; 6%). In the first 28 days, thrombocytopenia (Gr 3-4: 12.5%) and neutropenia (Gr 3-4: 94%) were common but there were no bleeding complications, and the rate of febrile neutropenia was 25%.

Investigators have planned a multicenter trial for treatment of B-cell malignancies including FL that will start enrollment in 2022 to further investigate the safety, efficacy, and durability of the third generation CAR T product MB-106.

REFERENCES
1. Shadman M, Yeung C, Redman M, et al. Efficacy and Safety of a third generation CD20 CART (MB-106) for treatment of relapsed/refractory follicular lymphoma (FL). Presented at: EHA 2022 Hybrid Congress, June 9-12, 2022.
2. Mustang Bio announces results from follicular lymphoma cohort of ongoing phase 1/2 clinical trial of MB-106, CD20-targeted CAR T therapy, selected for oral presentation at European Hematology Association 2022 Hybrid Congress. News release. Mustang Bio. May 12, 2022. https://firstwordpharma.com/story/5570779