S826 IMPROVED EFFICACY AND SAFETY OF A DUAL‐TARGET CAR‐T CELL THERAPY TARGETING BCMA AND CD38 FOR RELAPSED/REFRACTORY MULTIPLE MYELOMA FROM A PHASE I STUDY
Authors: C. Li, H. Mei, Y. Hu, T. Guo, L. Liu, H. Jiang, L. Tang, Y. Wu, L. Ai, J. Deng, D. Jin
Journal: HemaSphere (2019)

Background: Encouraging results are seen from several early phase clinical trials on the cellular immunotherapy for relapsed/refractory (RR) multiple myeloma (MM), including anti‐B cell maturation antigen (BCMA) CAR‐T cell therapy and anti‐CD38 daratumumab (DARA) monotherapy. We conducted an anti‐BCMA and anti‐CD38 dual‐target CAR‐T cell in order to avoid negative relapse of single‐target loss. Here we report a promising results on 12 patients about the efficacy and safety in the ongoing phase I study. Aims: 1.To evaluate the safety of the anti‐BCMA and anti‐CD38 dual‐target CAR‐T cell in RRMM, including cytokine release syndrome (CRS), neurotoxicity and other adverse events. 2.To assess the efficacy of the anti‐BCMA and anti‐CD38 dual‐target CAR‐T cell in RRMM, including the overall response rate(ORR),duration of remission and Progression‐free survival(PFS). 3.To estimate the proliferation and persistence of the dual‐target CAR‐T cell in the blood of RRMM patients. Methods: A phase I clinical trial (ChiCTR1800018143) has been launched to evaluate the efficacy and safety of the dual‐target CAR‐T cell product for RRMM. The enrolled RRMM patients had received at least 2 prior treatment regimens, including a proteasome inhibitor and an immunomodulatory agent, or are double‐relapsed or relapse after autologous hematopoietic stem cell transplantation(ASCT). Patients were subjected to a lymphodepleting regimen with Cy(250 mg/m 2 ,d‐5 to d‐3) and Flu(25 mg/m 2 ,d‐5 to d‐3) daily prior to the CAR‐T infusion (d0).The median number of infused cells was 2.17(0.5∼4.0) × 10 6 CAR + cells/kg. The median follow‐up times is 21.5(6∼33)weeks and 66.7%(8/12) are more than 5 months. The efficacy was assessed by the International Uniform Response Criteria for Multiple Myeloma(2016), and the toxicity was graded by CTCAE 5.0. Results: As of January 31, 2019, 12 patients consisting of 66.67%(8/12) with genetic abnormalities,16.7%(2/12) with ASCT and 16.7%(2/12) with extrandal disease, have been infused with thedual‐target CAR‐T cell product. The overall response rate(ORR) is 83.3%(10/12), including 5 sCR, 2 VGPR and 3 PR. the shortest duration of sCR is 8 weeks and the longest one is over 26 weeks and 60%(3/5) have still maintained sCR more than 2 month. More encouragingly, 60%(6/10) have still kept sustained remission and allextramedullary lesions have been eliminated.The 8‐week Progression‐free survival(PFS) is 0.90 and 12‐week PFS is 0.77. Up to now, the CAR‐T cells still exists in the patients’ peripheral blood by flow cytometry and q‐PCR. The peak time of CAR‐T cells proliferation of sCR patients is about the 2 nd week after infusion, which is earlier than other patients. 83.3%(10/12) were observed with cytokine release syndrome (CRS) and severe CRS(≥ Grade 3) accounted for 33.33%(4/12). No neurotoxicity was observed. Almost all the patients were observed with hematological toxicities. 16.7%(2/12) of patients was observed with hepatotoxicity and one patient with nephrotoxicity, which were relieved after symptomatic treatment. Summary/Conclusion: Our study demonstrates an improved efficacy with dual‐target CAR‐T therapy targeting BCMA and CD38 for RRMM with a high ORR, especially a higher rate and a longer duration of sCR. CRS and hematological toxicities are observed but manageable. Other toxicity is rare. These initial data provide strong evidence to support the further development of the dual‐target CAR‐T therapy for RRMM. ChiCTR1800018143 image