CAR T-Cell Therapy Shows Promise in Multiple Hematologic Malignancies

Multiple studies designed to evaluate chimeric antigen receptor (CAR) T-cell therapies in various hematologic malignancies appeared to show promise at the 61st American Society of Hematology (ASH) Annual Meeting & Exposition in Orlando, Florida. “This is a very encouraging space to watch as new agents become available,” Stephen M. Ansell, MD, PhD, from Mayo Clinic, said in an interview with ONCOLOGY. “…I think as a class this is a very promising approach.”

Anti-BCMA and CD38 Dual-Targeted CAR T-Cell Therapy

CAR T-cell therapy targeting both B-cell maturation antigen (BCMA) and CD38 induced promising responses among patients with multiple myeloma who were treated with at least 3 prior therapies and whose disease had spread outside of the bone marrow.¹ “This is the first clinical trial of anti-BCMA and CD38 dual-targeted CAR T-cell therapy in refractory multiple myeloma. Our study demonstrates improved efficacy and manageable safety,” Yu Hu, MD, PhD, of Union Hospital at Huazhong University of Science and Technology in Wuhan, China, said during a presentation to an audience at the 61st ASH Annual Meeting and Exposition.

The objective response rate was 90.1%, with 12 patients achieving a stringent complete response (sCR) as their best response, meaning that no plasma cells were detected in the bone marrow. Seven patients (31.8%) had a partial response (PR), meaning that the level of M-protein in their blood or urine was reduced but still detectable, with 2 achieving a very good partial response (VGPR). One patient had a minor response. Eighteen patients (81.8%) reached bone marrow minimal residual disease–negative status.

At the cutoff date of October 31, 2019, 19 patients were still alive with 10 still in an sCR, 1 with a VGPR, and 4 with PRs. Three patients experienced a relapse and 1 patient developed progressive disease.

ZUMA-2 Trial in Mantle Cell Lymphoma

Results from the ZUMA-2 trial indicated that patients with relapsed/refractory mantle cell lymphoma (MCL) resistant to prior therapies may benefit from treatment with KTE-X19, an autologous CD19-targeting CAR T-cell therapy.² In this multicenter phase II study of 74 patients, 93% responded to the CAR T-cell therapy, with 67% of participants achieving a complete response (CR). Currently, this is the highest reported rate of disease response in patients with prior Bruton’s tyrosine kinase inhibitor failure.

“High overall response rates, durable remissions at a year, and without any mortality attributed to the CAR T-cell therapy. This is a big deal. For patients with proliferative mantle cell lymphoma, for patients with p53 variant mantle cell lymphoma, we desperately need active therapies,” Bijal D. Shah, MD, of the Moffitt Cancer Center, said in an interview at the meeting.

Study investigator Michael Wang, MD, professor in the department of lymphoma and myeloma at the University of Texas MD Anderson Cancer Center, noted that responses occurred rapidly after KTE-X19 infusion, with a median time to response of 1 month (range, 0.8-3.1 months). Responses were also durable; the median duration of response had not been reached at the end of follow-up (8.6 months-not estimable). Fifty-seven percent of all evaluable patients, including 78% of those with a CR, remained in remission at data cutoff.

ZUMA-1 Trial in Refractory B-Cell Lymphoma

Axicabtagene ciloleucel (axi-cel; Yescarta) demonstrated improved overall survival (OS) for patients with refractory large B-cell lymphoma, according to a 3-year analysis of the pivotal phase II ZUMA-1 trial.³ The CAR T-cell therapy induced a median OS of 25.8 months. At a median follow-up of 39.1 months, the 3-year OS rate was 47% with axi-cel, with approximately 60% of patients having relapsed or progressed. In a previous 2-year analysis of the study data, the objective response rate was 83% and the complete remission rate was 58%. The 2-year OS rate was 51% and the 2-year progression-free survival rate was 39%. “These data are highly encouraging,” Sattva S. Neelapu, MD, department of lymphoma and myeloma, The University of Texas MD Anderson Cancer Center, said during a presentation of the findings.

References:

1. Li C, Mei H, Hu Y, et al. A bispecific CAR-T cell therapy targeting BCMA and CD38 for relapsed/refractory multiple myeloma: updated results from a phase 1 dose-climbing trial. Presented at: 61st American Society of Hematology Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL. Abstract 930.

2. KTE-X19: A CAR T-cell option for mantle cell lymphoma? [news release]. Orlando, Florida. Published December 10, 2019. ashclinicalnews.org/on-location/ash-annual-meeting/kte-x19-car-t-cell-option-mantle-cell-lymphoma/. Accessed January 12, 2020.

3. Neelapu SS, Rossi JM, Jacobson CA, et al. CD19-loss with preservation of other B cell lineage features in patients with large B cell lymphoma who relapsed post–axi-cel. Presented at: 61st American Society of Hematology Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL. Abstract 203.