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CD20-Targeted CAR T-Cell Therapy Shows Safety, Good Response Rates in B-Cell Non-Hodgkin Lymphoma

A phase 1/2 multicenter study is underway following MB-106’s IND approval.

Results of an ongoing phase 1/2 clinical trial of CD20-targeted CAR T-cell therapy in B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia show good response rates and a favorable safety profile. The findings were presented at the Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR (2022 Tandem Meetings), held in Salt Lake City, Utah, and virtually April 23-26, 2022.

The single-center study, led by Mazyar Shadman, MD, MPH, of Fred Hutchinson Cancer Research Center, is evaluating MB-106 (Mustang Bio), a fully human, 3rd-generation CD20-targeted CAR T product with both 4-1BB and CD28 costimulatory domains across 4 dose levels: 3.3x105; 1x106; 3.3x106; 1x107 CAR T cells/kg.

Following lymphodepletion with cyclophosphamide and fludarabine, 16 patients were treated. Participants had previously treated R/R lymphoma and had failed at least 1 other treatment prior.

Between December 2019 and July 2021, the 16 participants (12 FL, 2 MCL, 1 CLL, 1 DLBCL)reached all dose levels with no dose-limiting toxicities observed. Notably, cytokine release syndrome (CRS) occurred in 44% of patients (n = 7), of which 4 had grade 1 and 3 had grade 2 (median time to occurrence, 6.5 days), and 1 patient experienced grade 2 immune effector cell-associated neurotoxicity syndrome (ICANS; occurrence on day 12). Although immune effector cell-associated neurotoxicity syndrome is an ongoing challenge, Notably, no grade 3 to 4 CRS or ICANS occurred. In addition, 1 patient experienced grade 3 temporary neuropathic pain, and no cases of tumor lysis syndrome or grade 3 or 4 infections were reported.

Investigators reported an overall response rate (ORR) of 94%, with 62% of patients achieving complete response (CR) and 31% achieving partial response (PR). All but 1 complete response are ongoing as of the data cutoff. Among the 12 patients with follicular lymphoma, ORR was 92% (11/12), CR was 75% (9/12), and PR was 17% (2/12). A PET-negative CR and undetectable measurable residual disease in peripheral blood and bone marrow at day 28 was recorded for the single patient with chronic lymphocytic leukemia; 1 patient with diffuse large B-cell lymphoma recorded a partial response on day 28, with PET imaging on about day 90 showing continued improvement; and 2 patients with mantle cell lymphoma recorded partial responses. Complete response rate was higher (86%) among those who received dose levels 3 or 4. Among the treated patients, 1 has thus far lost CAR-T persistence at day 95 and 2 lost CAR-T engraftment by day 181 and 201, respectively. As of last follow-up (approximately 13 months post-infusion), all other patients continue to have detectable CAR-T cells.

“MB-106 has been demonstrating compelling clinical activity and a favorable safety profile in the ongoing Phase 1/2 trial at Fred Hutch for patients with relapsed or refractory B-NHL and CLL,” said Manuel Litchman, MD, president and chief executive officer of Mustang Bio, in a statement. “Looking ahead, Mustang intends to dose 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.”

REFERENCES
1. Shadman M, Yeung CCS, Lee SY, et al. High Efficacy and Low Toxicity of MB-106, a Third Generation CD20 Targeted CAR-T for Treatment of Relapsed/Refractory B-NHL and CLL. Presented at: Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR (2022 Tandem Meetings). April 23-26, 2022; Salt Lake City, UT.
2. Mustang Bio Announces Upcoming MB-106 CD20-Targeted CAR T Data Presentations. News release. Mustang Bio. April 21, 2022. https://www.globenewswire.com/news-release/2022/04/21/2426502/0/en/Mustang-Bio-Announces-Upcoming-MB-106-CD20-Targeted-CAR-T-Data-Presentations.html