Mustang Bio’s CAR-T MB-106 Achieves Responses in Waldenstrom Macroglobulinemia, Follicular Lymphoma

Mustang Bio’s and Fred Hutchinson Cancer Center (Fred Hutch)’s MB-106, an investigational CD20-directed autologous chimeric antigen receptor (CAR) T-cell therapy being evaluated in a single-center phase 1/2 clinical trial (NCT03277729) at Fred Hutch, has achieved responses in 2 separate cohorts for patients with Waldenstrom macroglobulinemia (WM) and follicular lymphoma (FL), respectively.^1-3

The data from the WM cohort was reported in a poster presentation at the European Hematology Association (EHA) 2023 Congress, held June 8 to 11, both virtually and in Frankfurt, Germany. Among the 6 patients in the WM cohort, the overall response rate (ORR) was 83% (n = 5). Two patients achieved a complete response (CR), 1 patient achieved a very good partial response, 1 patient achieved a partial response, and 1 patient achieved a minor response. It was additionally noted that 1 patient showed stable disease. Mustang Bio stated that 1 of the patients who achieved a CR continued to be in remission at 22 months posttreatment. This patient also experienced a sustained reduction in immunoglobulin M to normal levels following administration of MB-106. Furthermore, none of the 6 patients began treatment with additional anti-WM therapies following treatment with MB-106.

In terms of safety, 2 patients experienced cases of grade 1 cytokine release syndrome (CRS) and 3 patients experienced grade 2 cases of CRS. A single case of grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS) was reported in 1 patient. No higher grade cases of CRS or ICANS occurred. Other grade 3 to grade 4 adverse events reported included leukopenia (83% of patients), neutropenia (100%), lymphopenia (83%), thrombocytopenia (33%), hypotension (33%), hypertension (16%), fatigue (16%), elevated alanine transaminase (16%), and elevated aspartate aminotransferase (16%). The ages of the 6 patients in the cohort ranged from 51 years to 79 years (median, 69) and the group included 2 women (33%). The number of prior lines of therapy received by the patients ranged from 2 to 12 (median, 7.5). It was noted that all 6 of the patients had experienced progression during prior treatment with Bruton tyrosine kinase inhibitors. MB-106 previously received FDA orphan drug designation for WM in June 2022.

“As we continue to evaluate MB-106 in this single-institution study, we’re encouraged by its potential to become an outpatient treatment option for WM and other B-cell malignancies, including indolent and aggressive non-Hodgkin lymphomas,” Mazyar Shadman, MD, MPH, an associate professor and physician at Fred Hutch and University of Washington, said in a June 12, 2023, statement.² “We have observed ongoing responses to MB-106 with improvements in the quality of response over time, along with a favorable safety profile.”

Among 20 patients in the FL cohort who had at least 28 days of follow-up, the ORR was 95% (n = 19) with a CR rate of 80% (n = 16).³ Among a subset of patients who were treated at the 2 highest dose levels (3.3x10⁶ cells/kg and 1.0x10⁷ cells/kg) the ORR was 100% with a CR rate of 91%. Moreover, Mustang Bio noted that 10 of the patients in the cohort had remissions that have continued for more than 1 year and that 7 of these patients’ remissions have continued formore than 2 years. The company also highlighted the case of 1 patient who had been previously treated with a CD19-direct CAR-T therapy, who achieved a CR with MB-106, and has continued to be in remission for 18 months.

In terms of safety, there were 5 cases of grade 1 CRS and 1 case of grade 2 CRS reported. No grade 3 or higher CRS nor any cases of ICANS were reported in this cohort. The ages of the patients in the cohort ranged from 44 years to 81 years (median, 63) and the number of prior lines of treatment received ranged from 1 to 12 (median, 4). Fifteen of the patients (75%) had had disease progression within 24 months of their first-line chemotherapy and 4 patients (20%) had a history of histologic transformation. Mustang Bio noted that the data from the FL cohort were presented at the 17th International Conference on Malignant Lymphoma (17-ICML).

"We are encouraged by the MB-106 data from the FL cohort presented by Dr Shadman at 17-ICML from the Fred Hutch phase 1/2 clinical trial, as well as the data from the Waldenstrom macroglobulinemia cohort that he recently presented at the European Hematology Association 2023 Hybrid Congress,” Manuel Litchman, MD, the president and CEO of Mustang, said in a June 15, 2023, statement.³ “The data underscore the great potential of MB-106 to treat a range of hematologic malignancies. We look forward to reporting initial data from our multicenter phase 1/2 clinical trial of MB-106 shortly.”

REFERENCES
1. Shadman M, Yeung C, Redman MW, et al. CC20 CAR-T therapy with MB-106 for BTK inhibitor-refractory Waldenström macroglobulinemia (wm)/ lymphoplasmacytic lymphoma (lpl) – single institution study. Presented at: the European Hematology Association (EHA) 2023 Congress, June 8-11, held both virtually and in Frankfurt, Germany. Abstract #P1097
2. Mustang Bio announces updated results from Waldenstrom macroglobulinemia cohort of ongoing phase 1/2 clinical trial of MB-106, CD20-targeted autologous CAR T therapy. News release. Mustang Bio, Inc. June 12, 2023. Accessed June 16, 2023. https://ir.mustangbio.com/news-events/press-releases/detail/160/mustang-bio-announces-updated-results-from-waldenstrom
3. Mustang Bio announces final results from follicular lymphoma cohort of single-institution phase 1/2 clinical trial of MB-106, CD20-targeted autologous CAR T therapy. News release. Mustang Bio, Inc. June 15, 2023. Accessed June 16, 2023. https://ir.mustangbio.com/news-events/press-releases/detail/161/mustang-bio-announces-final-results-from-follicular