CD19 targeted CAR-T therapy versus chemotherapy in re-induction treatment of refractory/relapsed acute lymphoblastic leukemia: results of a case-controlled study

Abstract

Chimeric antigen receptor modified T cells against CD19 (CART19s) have potent anti-leukemia activities in patients with refractory/relapsed acute lymphoblastic leukemia (R/R ALL). This study was designed to investigate the correlation between safety/efficacy and therapeutic modalities including chemotherapy and CART19 therapy. Total 23 and 69 patients were enrolled in the CART19 group and in the chemotherapy group, respectively. The safety and efficacy profiles of 66 and 22 patients in the 2 groups were evaluated. The complete remission (CR) rate was higher in the CART19 group than that in the chemotherapy group (90.9 vs 37.9%, P = 0.000). For patients relapsed after allo-HSCT and chemotherapy, CR rates were 100% (8/8) vs 48.0% (12/25) (P = 0.009) and 85.7% (12/14) vs 31.7% (13/41) (P = 0.000), respectively. Moreover, a higher percentage in the CART19 group had results below the threshold for minimal residual disease (100 vs 7.58%, P = 0.000). In survival analysis, the overall survival rate at 12 months was higher in the CART19 group than that in the chemotherapy group (60.9 vs 10.1%, P = 0.000). For post-transplant patients achieving CR, 25.0% (2/8) and 75.0% (9/12) complicated with GVHD (P = 0.04) in the CART19 group and chemotherapy group, respectively. For all CR patients, the median duration of absolute neutrophil count less than 500/μL and platelet count less than 20,000/μL were longer in the CART19 group than in the chemotherapy group (p = 0.0047 and 0.0003, respectively). Our data demonstrated that patients with CART19s therapy acquired higher rates of remission and longer survival, confirming the encouraging application of CART19 therapy in R/R ALL.

Treatment response, survival, safety, and predictive factors to chimeric antigen receptor T cell therapy in Chinese relapsed or refractory B cell acute lymphoblast leukemia patients

“…The application of CAR-T has been implicated in acute leukemia and non-Hodgkin's lymphoma, and it has made prominent progress in B-ALL during the past several years. Clinical studies in the United States and Europe illustrate that the CR rate to CAR-T therapy is around 90% in R/R B-ALL patients, which is similar to that in de novo B-ALL patients [8][9][10][11][12][13][14] . The survival profiles of R/R B-ALL patients have also been improved by CAR-T therapy, but with inevitable adverse events (such as cytokine release syndrome (CRS), B cell aplasia, neurotoxicity, and tumor lysis syndrome) 15,16 .…”

Improving the safety of CAR-T cell therapy by controlling CRS-related coagulopathy

“…In CD19-positive B cell malignancies, approximately 90% acute lymphoblastic leukemia (ALL) patients [1][2][3][4][5][6][7][8][9][10][11][12] and 70% lymphoma patients [13][14][15][16][17][18] can get remissions through CD19-specific CAR-T therapy. Encouragingly, two of the CD19-targeted CAR-T therapies, Kymriah and Yescarta, have been approved to treat relapsed/refractory (r/r) pediatric, young adult B cell ALL (B-ALL), and certain adult non-Hodgkin lymphomas (NHL) by the US Food and Drug Administration in 2017.…”

The efficacy of anti-CD19 chimeric antigen receptor T cells for B-cell malignancies

“…First, we compared the clinical responses among malignancies type (ALL, CLL and lymphoma). For ALL, RR of 81% (223/277) was observed, with an HR of 0.80 (95% CI: 0.68À0.88, P = 0.000) in 14 clinical trials [25][26][27][28][29]32,35,38,41,46,48,50,52,53]. There was significant heterogeneity among the studies with an I 2 of 64, Q = 36 ( Figure 3).…”

“…Thus, ALL patients had higher response rate (81%) than CLL patients (70%) and lymphoma patients (68%) (Figure 3). [20,27,30,34,37,46,52]. There was significant heterogeneity among the studies, with an I 2 of 58, Q = 14 ( Figure 4).…”

“…Eleven clinical trials reported CR and PR [28,30,35,36,39,42,43,45,51,52,54], in addition another 27 clinical trials reported CRe and PRe [17À29, 31,32À34,37,38,40,41,44,46À50,53]. In two clinical trials, only remission was reported [17,22], and we calculated them as CRe and PRe.…”