-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

4852 Safety and Efficacy of a Locally Produced Novel Anti-BCMA Chimeric Antigen Receptor T-Cell (CART) (HBI0101) for the Treatment of Relapsed and Refractory Multiple Myeloma

Program: Oral and Poster Abstracts
Session: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: Poster III
Hematology Disease Topics & Pathways:
Biological therapies, Plasma Cell Disorders, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, Therapies, Lymphoid Malignancies
Monday, December 11, 2023, 6:00 PM-8:00 PM

Eyal Lebel1,2*, Nathalie Asherie2*, Shlomit Kfir-Erenfeld2,3*, Batia Avni, MD3,4*, Sigal Grisariu, MD2,4*, Shlomo Elias2,3, Miri Assayag2,3*, Tatyana Dubnikov2,3*, Nomi Zalcman3,5*, Marjorie Pick3*, Eran Zimran, MD2,3*, Yael C. Cohen6,7*, Irit Avivi Mazza, MD8*, Cyrille Cohen9*, Moshe E Gatt, MD3,10 and Polina Stepensky2,3*

1Faculty of Medicine, the Hebrew University, Jerusalem, Jerusalem, Israel
2Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah Medical Center, Jerusalem, Israel
3Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
4Bone Marrow Transplantation & Cancer Immunotherapy Department, Hadassah-Hebrew University Medical Center and Faculty of Medicine, the Hebrew University of Jerusalem, Jerusalem, Israel
5Bone marrow transplant and cellular therapy department, Hadassah Medical Center, Jerusalem, Israel
6Department of Hematology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
7Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
8Hematology Division, Sourasky Medical Center and the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
9Laboratory of Tumor Immunology and Immunotherapy, The Mina and Everard Goodman Faculty of Life Sciences,, Bar-Ilan University, Ramat Gan, Israel
10Department of Hematology, Hadassah Medical Center, Jerusalem, Israel

BACKGROUND: Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CART) therapy shows remarkable efficacy in patients with relapsed and/or refractory (R/R) multiple myeloma (MM), with recent phase 3 studies showing clear advantage of idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) over standard-of-care. However, access to these commercial CART products is a major barrier, and it is estimated that only around a quarter of eligible R/R MM patients will receive CART nowadays.

HBI0101 is a novel second generation optimized anti-BCMA CART with 4-1BB co-stimulatory domain, that was developed in an academic setting, at Hadassah Medical Center and Bar-Ilan University. The phase Ia study evaluating HBI0101 (NCT04720313) demonstrated a manageable safety profile and an initial high efficacy (Asherie, Haematologica 2022). Here, we present the updated results of 50 patients receiving 800x10^6 CART cells in the NCT04720313 phases 1a-b / 2.

METHODS: The phase 1a study with HBI0101 which first evaluated 20 R/R MM patients with ≥3 prior lines of therapy, including a PI, IMiD and anti-CD38 antibody, revealed a dose of 800x10^6 CART cells to be safe and effective. The phase Ib and phase 2 of the study evaluated this dose infusion in 43 additional patients. Inclusion criteria were relatively permissive with minimum creatinine clearance of 20ml/min, platelet count of 30x109/ml, left ventricular ejection fraction of 40%, and ECOG performance status of ≤2. Lymphodepletion included fludarabine 25mg/m2 and cyclophosphamide 250mg/m2 on days -5 to -3 before infusion (bendamustine 90mg/m2 and on days -4 and -3 for patients with creatinine clearance <30ml/min). Planned manufacturing time was 10 days.

RESULTS: Of 51 patients who underwent lymphocyte apheresis, 50 (98%) were treated with 800x10^6 CART cells; 7 patients in the phase Ia cohort and 43 in the phases 1b / 2 cohorts. HBI0101 production success rate was 100%, with manufacturing time of 10 days for all patients. The median age was 65y (range 40-84). The median number of prior lines was 4 (range 3-13) and most patients (47/50, 94%) were triple refractory to PI, IMiD and anti-CD38 antibody. Twenty patients (40%) were penta-refractory and 10 (20%) were refractory to the anti-BCMA antibody drug conjugate belantamab mafodotin. Forty-six patients (92%) were refractory to the last line of therapy. Twelve patients (24%) had high risk cytogenetics (t(4:14), t(14:16) or deletion 17p); 31 (62%) when 1q gain included. Sixteen patients (32%) had extramedullary involvement at study entry.

Grade 3-4 hematological toxicities were common (anemia- 62%, thrombocytopenia- 54%, neutropenia- 98%, lymphopenia- 100%). Cytokine release syndrome (CRS) occurred in 48/50 (96%)- grade 1/2- 17 patients (82%); grade 3- 7 patients (14%). Tocilizumab was used in 40/48 patients with CRS (median of 1 dose, range 1-4) and corticosteroids in 8/48. Two cases of immune effector cell associated neurotoxicity syndrome (ICANS) were observed (grade 1 and 2). Two patients developed CART-associated hemophagocytic lymphohistiocytosis syndrome (HLH). No irreversible organ toxicities or treatment related deaths occurred.

The overall response rate (ORR) was 45/50 (90%), including 29 patients (58%) with complete response (CR)/stringent CR, 10 (20%) with very good partial response and 6 (12%) with partial response. Thirty-five patients (70%) achieved minimal residual disease (MRD) negativity at day +30. At a median follow-up of 11.9 months (range: 0.6-19), the median progression-free survival was 10.6 months, and the median overall survival was not reached (Figure 1).

Although the presence of extra-medullary disease and prior anti-BCMA therapy correlated with worse outcome, high response rates were still observed (ORR of 98%/75% for patients without/with extra-medullary disease, respectively, and 95%/75% for patients without/with prior anti-BCMA therapy, respectively). Updated results will be communicated at the presentation time.

CONCLUSION: Our findings demonstrate the manageable safety and high efficacy profiles of HBI0101 also in high-risk patients. Fast production time enabled the timely treatment of 98% of apheresed patients. These favorable data are encouraging and support decentralization of CART production at an academic setting, ensuring a sufficient CART supply in the light of the increasing demand.

Disclosures: Cohen: Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Avivi Mazza: AbbVie: Honoraria.

*signifies non-member of ASH