612. Acute Lymphoblastic Leukemia: Clinical Studies: Innovative Chemotherapy and Immunotherapy Strategies in Frontline and Relapsed Disease
David T. Teachey, Meenakshi Devidas, Brent L Wood, et al
Authors Conclusion from the Abstract: Outcomes for SR and IR pts with T-ALL and T-LL treated with bortezomib were excellent despite the elimination of prophylactic CXRT. Bortezomib significantly improved 3-year EFS for these groups, comprising ~95% of pts. Outcomes for VHR pts were dismal and worse on the bortezomib arm. T-LL pts had significantly improved EFS and OS with bortezomib on the AALL1231 backbone. This is the first trial to demonstrate an OS benefit for de novo pediatric T-LL with a new agent; however, longer follow-up is needed. Therapy intensification allowed elimination of CXRT in the majority of pts without excessive relapse. These results should be interpreted cautiously as the 3-yr OS on AALL1231 was inferior to AALL0434. Nevertheless, incorporating bortezomib into standard therapy for de novo T-LL appears advantageous. Future COG T-ALL/T-LLy trials will build on the positive findings from AALL0434 and AALL1231, balancing intensity while mitigating toxicity to maintain high cure rates without routine cranial radiation. (MLL, SPH, EAR contributed equally)
Matthias Stelljes, Simon Raffel, Ralph Wäsch, et al.
Authors Conclusion from the Abstract: Replacement of conventional induction chemotherapy by InO is feasible, results in promising remission rates, and may reduce the risk of early morbidity and lethality, particular in older patients with acute B lymphoblastic leukemia.
Franco Locatelli, Gerhard Zugmaier, Carmelo Rizzari, et al.
Authors Conclusion from the Abstract: Blinatumomab monotherapy as consolidation therapy before alloHSCT in children with HR first-relapse BCP-ALL leads to significantly better EFS, lower risk of recurrence, and fewer grade ≥ 3 treatment-emergent AEs vs HC3, suggesting a new standard‑of-care treatment for these patients.
Agne Taraseviciute, Seth M. Steinberg, Regina M. Myers, et al
Authors Conclusion from the Abstract: This large, multicenter analysis demonstrate an association with blina use and 1) increased risk of CAR non-response; 2) worse RFS and EFS and 3) a trend towards a higher incidence of pre-CAR CD19 dim disease. While blina non-response did not preclude CD19 CAR response, blina non-responders had lower remission rates to CD19 CAR and a cohort of patients were refractory to both, potentially suggesting resistance to immunotherapeutic CD19 targeting. Additionally, we found that blina may impact CD19 expression, which could subsequently affect response and relapse. Mechanisms of resistance to CD19 CAR include antigen escape or an inherent resistance to T-cell mediated killing. Our data suggest that 1) patients relapsing after or refractory to blina who proceed to CD19 CAR may have an inherent resistance and 2) blina may impact CD19 expression. Ongoing analysis includes detailed analysis of low/dim/partial CD19 expression to delineate the potential impact of blina exposure on leukemic blasts and evaluation of the role of HSCT.
Xian Zhang, Jiasheng Wang, Yue Liu, et al
Authors Conclusion from the Abstract: This study demonstrates the superiority of STAR T-cells compared to conventional CAR T-cells in terms of signaling capacity, cytokine production capability and anti-tumor potency in an animal model. The Phase I first-in-human study demonstrated technical feasibility, clinical safety and efficacy of STAR-T in treating CD19+ R/R B-ALL. A high CR could be achieved on day 14 with low toxicity. Longer-term observation of these patients and studies of larger patient cohorts are warranted.
Giacomo Gotti, Maneka Puligandla, Kristen E. Stevenson, et al
Authors Conclusion from the Abstract: Our findings provide insight into the prognostic significance of the most common mutations in pediatric HHD B-ALL in a uniformly treated cohort of patients as part of the DFCI ALL Consortium. The presence of CREBBP and clonal Ras pathway mutations may be associated with upfront chemotherapy resistance as demonstrated by high end-induction MRD. Further analysis of Ras pathway mutations segregated by VAF is warranted. Future trials may integrate these findings into risk stratification of HHD ALL. With prospective continued clinical use of NGS assays, we will further clarify the role of mutations and their contribution to disease outcomes in B-ALL.