Ps940 Combination Bcl-2 Inhibitor Therapy With Venetoclax and Navitoclax in Patients With Relapsed/refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma
Year: 2019
Type: conference-abstract
Abstract: Background: In recent decade, CAR-T cell therapy has surprisingly improved the response rate of refractory and relapsed patients with acute lymphoblastic leukemia (ALL). However, there are still 10∼20% of patients who failed to respond to the treatment, and disease recurrence remains the major concern for patients even achieving remission. Thus, studies focusing on long-term outcomes are warranted. Aims: To investigate the efficacy and safety of CAR-T cell therapy in unremission ALL patients, and to explore the role of the strategy of CAR-T cell bridging to allogeneic hematopoietic cell transplantation (HCT). Methods: A clinical trial was conducted with following inclusion criteria: 1) ALL patients with a disease status out of remission; 2) CD19/CD22 were expressed on leukemic cells; 3) tolerant to intensive treatments. Patients enrolled received preparative treatment of fludarabin and cyclophosphamide, and followed by infusion of CAR-T cells targeting to CD19/CD22 with a target dose of 5∼10 × 106/kg of recipient weight. HCT procedures were performed after the evaluations, which were at 4 weeks after the CAR-T cell therapy. Results: In total, 85 patients were enrolled and received CAR-T cell therapy (details in the table). Complete remission (CR) was attained in 65 patients and partial remission in another 4 patients. Except 4 cases died before evaluation, the CR and overall response rate (ORR) for patients in per protocol set were 80.2% and 85.2% respectively. Among the CR patients, 48 cases were measurable residual disease (MRD) negative, which produced a MRD response of 59.3%. Previous HCT history had a negative impact on the MRD response (P = 0.036). Cytokine-release syndrome (CRS) was observed in 65 cases (76.5%), but only 27 cases (31.8%) were assessed as grade 3 or higher. Higher blast proportion in marrow was related to increased risk for CRS grade≥2 (P = 0.002). Early death (died in first three months after CAR-T cell infusion) occurred in 12 patients, who were excluded from the survival analyses. One-year overall survival (OS) and progression-free survival (PFS) of the rest 73 cases were 53.4% ± 5.9% and 46.4% ± 5.8% respectively. Twenty-four cases who received sequential allogeneic HCT had remarkably improved 1-year OS (79.9% ± 9.2% versus 46.7% ± 7.8%, P < 0.001) and PFS (73.7% ± 9.3% versus 41.2% ± 7.5%, P < 0.001) than the ones without HCT (as shown in the figure), although responses to CAR-T cell therapy was comparable between these two groups of patients. Cox regression results showed allogeneic HCT was a significant impactor for OS (HR 3.606, P = 0.018) as well as PFS (HR 2.901, P = 0.011).Summary/Conclusion: Our data showed, for B-cell ALL patients out of remission, CAR-T cell therapy targeting to CD19/CD22 had a promising response but long-term outcome remained poor. Sequential allogeneic HCT may dramatically improve the OS and PFS, which needs to be further validated by randomized studies.
Source: HemaSphere
Authors: V.A. Pullarkat, W. Stock, N.J. Lacayo, E. Jabbour, A. Bajel, J. Rubnitz, J. Leonard, C.G. Mullighan, S.L. Khaw, S.I. Vear, A. Salem, M. Schmidt, B. Tong, Y. Zhou, J.A. Ross, L. Bensman, A. Jacobson, T. Alexander, R. Norris
Institution: First Affiliated Hospital of Soochow University
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,480
OpenAlex ID: W2950556060