Acute Lymphoblastic Leukemia: Therapy, excluding Transplantation: Targeted Therapy in ALL: Immunotherapy and Beyond
553 Sequential Combination of Low-Intensity Chemotherapy (Mini-hyper-CVD) Plus Inotuzumab Ozogamicin with or without Blinatumomab in Patients with Relapsed/Refractory Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia (ALL): A Phase 2 Trial
Koji Sasaki, et al.
The Abstract concludes: The combination of inotuzumab ozogamicin plus/minus blinatumomab with low-intensity mini-hyper-CVD chemotherapy is effective and shows encouraging results in patients with relapsed/refractory ALL. The risk of VOD can be minimized with fractionated inotuzumab ozogamicin dosing.
554 Blinatumomab for Minimal Residual Disease (MRD) in Adults with B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL): Median Overall Survival (OS) Is Not Reached in Complete MRD Responders at a Median Follow-up of 53.1 Months
Nicola Goekbuget, et al.
The Abstract concludes: In this multinational study of adults with BCP-ALL in hematologic complete remission with persistent MRD or MRD relapse at baseline, median OS was 36.5 months after blinatumomab treatment, with median long-term follow-up of 53.1 months, and OS reached a plateau. Median OS was not estimable (ie, not reached) among the patients who had achieved a complete MRD response after cycle 1 of blinatumomab treatment, or among the subsets of patients who had achieved a complete MRD response with blinatumomab either in CR1 or with subsequent HSCT in CCR. These results provide further support for the long-term benefits in OS associated with blinatumomab treatment in adults with BCP-ALL and MRD.
555 A Phase 2 Study of Ruxolitinib with Chemotherapy in Children with Philadelphia Chromosome-like Acute Lymphoblastic Leukemia (INCB18424-269/AALL1521): Dose-Finding Results from the Part 1 Safety Phase
Sarah K. Tasian, et al.
The Abstract concludes: These findings demonstrate safety and tolerability of ruxolitinib in combination with intensive multi-agent chemotherapy in children and AYAs with newly-diagnosed HR CRLF2-R/JAK pathway-mutant Ph-like ALL and support continued investigation of treatment efficacy in Part 2 of this trial.
Amanda M. Li, et al.
The Abstract concludes: T cell exhaustion or activation induced CAR T death (AICD) has been suspected to contribute to poor persistence of CAR T cells. We hypothesized that the PD-1 checkpoint pathway may be involved in CAR T cell exhaustion in some cases, which may be overcome by checkpoint inhibition. Here, promising responses were specifically seen in those with early B-cell recovery and bulky extramedullary disease. In contrast, PD-1 inhibition had partial, but no durable, effect in the four B-ALL patients with poor initial marrow response to CAR T cell therapy alone, suggesting a different mechanism such as AICD may be responsible for poor initial responses. No unexpected or fatal toxicities were seen. This cohort shows initial evidence that checkpoint inhibitors can be used effectively and safely with CAR T cell therapy in children with relapsed B-ALL, and that this strategy may augment CAR T cell effect and persistence.
557 Blinatumomab in Combination with Immune Checkpoint Inhibitors of PD-1 and CTLA-4 in Adult Patients with Relapsed/Refractory (R/R) CD19 Positive B-Cell Acute Lymphoblastic Leukemia (ALL): Preliminary Results of a Phase I Study
Jonathan Webster, et al.
The Abstract concludes: Combination therapy with blinatumomab and nivolumab in R/R ALL with is feasible with acceptable toxicity. The MRD-negative CR rate was (80%) despite heavily pre-treated patients with significant baseline disease burden. The last patient treated at DLA1 is undergoing treatment before dose escalation to include ipilimumab.
Matthew J. et al.
The Abstract concludes: In a retrospective analysis of pediatric MPAL, the majority of patients treated with ALL chemotherapy achieved a MRD-negative CR by EOC (~week 12 of therapy); overall survival in this group was excellent. Further prospective validation of MRD is essential to refine risk-stratified therapy for pediatric MPAL. Optimal salvage for those who fail to achieve remission with ALL chemotherapy is unknown and requires further study.