Highlights from

ASH 2019

61st Annual Meeting & Exposition of the American Society of Hematology

Orlando, Florida (USA) 7 - 10 December 2019

Anti-BCMA/anti-CD38 in refractory multiple myeloma

In the first clinical trial of a novel, bispecific anti-BCMA and CD38 dual-targeted chimeric antigen receptor (CAR) T-cell therapy in refractory multiple myeloma, results demonstrated promising responses and a manageable safety profile [1].

The dose-escalation phase 1 trial, presented by Prof. Yu Hu (Huazhong University of Science and Technology, China), included 22 patients with multiple myeloma that had returned or not responded to at least 3 prior therapies. Of the 22 patients, 9 (41%) had extramedullary tumours. Myeloma cells in the bone marrow were observed at a median of 9.7% (0.50% to 56.1%) by flow cytometry; and 73% of patients had cytogenetic abnormalities such as amplified 1q21 (54.6%) or deletion of chromosome 13q (40.9%).

All patients were treated with fludarabine at 25 mg/m2 and cyclophosphamide 250 mg/m2 before infusion with the engineered CAR T cells. Patients were infused with CAR T cells at 0.5 × 106/kg to 4.0 × 106/kg with at least 2 patients treated at every dose level.

The objective response rate was 90.1%, with 12 patients achieving a stringent complete response (sCR) as their best response. Seven patients (31.8%) had a partial response (PR), with 2 patients achieving a very good partial response (VGPR). One patient had a minor response. Furthermore, 18 patients (81.8%) reached bone marrow minimal residual disease-negative status.

At the cut-off date of 31 October 2019, 19 patients were still alive, with 10 stably maintaining sCR, 1 with VGPR, and 4 with PRs. Only 3 patients experienced relapse and 1 patient had progressive disease. The median progression-free survival (PFS) had not been reached; at 9 months PFS was 78.9%. For the 17 patients remaining in remission at 7 months after treatment, the median duration of response was 28.8 weeks.

Cytokine release syndrome (CRS) was observed in 20 out of 22 patients (90.9%); most were not severe with 11 having grade 1 CRS and 4 with grade 2. Severe CRS grade ≥3 occurred in 5 (22.7%). Only 6 patients overall required treatment for CRS. No neurotoxicity was observed. Hepatotoxicity was seen in 3 patients (13.6%) and 1 patient experienced nephrotoxicity.

Of the 9 patients with extramedullary disease, 8 achieved complete or partial response undetectable by CT scan. Follow-up on these patients will continue for 2 years, at which point these preliminary data points will be revised.

Keywords: Multiple Myeloma; Adoptive Immunotherapy; Chimaeric Antigen Receptors; BCMA

Top image: @ iStockPhoto: ustas7777777

The content and interpretation of these conference highlights are the views and comments of the speakers/authors.