614. Acute Lymphoblastic Leukemia: Therapy, excluding Transplantation: Chemo Immuno and Targets--Improving Combinations in ALL


Adele K. Fielding, et al.

Conclusion cited from the abstract:  The non-significant trend to a better outcome with SOC+R underscores the necessity for including 16-18 doses of rituximab to obtain the full benefit. However, our trial shows no treatment interaction of SOC+R with Ph+ status or CD20+ expression level, suggesting that the GRAALL-2005/R results may possibly be generalizable to all patients with B-precursor ALL.




Conclusion cited from the abstract: In the first chemo-free induction-consolidation protocol for adult Ph+ ALL patients of all ages based on a combination of a targeted and immunotherapeutic strategy, the rates of molecular responses and survival are highly promising; patients harboring IKZF1 plus represent, also in this setting, a clinical challenge.



Conclusion cited from the abstract: InO demonstrated a CR/CRi rate of 58% in these heavily pretreated children and young adults with R/R CD22-positive B-ALL. In responders, 65.4% achieved MRD <0.01%. Minimal hepatic toxicity was observed during InO therapy. SOS occurred in 30.7% of pts who underwent subsequent HSCT (8.3% of pts overall), and all but 1 case resolved quickly with supportive care and defibrotide. The most common DLT was prolonged marrow aplasia. Given the observed efficacy, InO will be incorporated into a randomized phase 3 trial for newly diagnosed pediatric pts with high-risk B-ALL.



Conclusion cited from the abstract: 

The NOPHO ALL2008 stratification strategy led to allocation of 16% of patients to the HR arm with an EFS of 67% and OS of 74%. Due to the intensity of chemotherapy a significant risk of toxic death was encountered, and the risks of toxic death and relapse were very similar. Patients with rearranged KMT2A and a low EOI MRD could be candidates for future reduction of treatment intensity. These findings are integrated into the upcoming European ALLTogether1 protocol opening in 14 European countries early 2020, where the use of the NOPHO ALL2008 HR blocks will be restricted to the 3% of patients with the poorest prognosis.


Figure – EFS with 95% Cis, CITRM (short dash) and CIR (long dash) for the NOPHO ALL-2008 high-risk chemotherapy patients



Conclusion cited from the abstract: 

In this study, we reduced the relapse and toxicity before alloHCT, and improved the EFS and OS at 3 years. JALSG is starting a Ph+ALL219 phase II study to introduce ponatinib for patients who did not achieve CMR after INC following the schedule in the Ph+ALL213 study.



Conclusion cited from the abstract: The combined pediatric and adult phase I trials of bispecific CD19/CD22 targeting CAR T cells in relapsed/refractory ALL demonstrates safety and tolerability at two dose levels. Expanded accrual at dose level 2 is ongoing and clinical outcomes will be updated. This work additionally demonstrates feasibility of delivering unified B-ALL CAR T cell therapy across age boundaries. Multi-parametric CyTOF studies permitting CAR T cell phenotyping in conjunction with single cell TCR tracking, proteomics, epigenomics and cytokine profiling are ongoing and will be used to further characterize persisting CAR T cells and define inter-product and inter-patient variability.




Roberta Demichelis, et al.

Conclusion cited from the abstract: Although different groups have shown the benefit of PIR in the AYA-patients, the MD Anderson group couldn´t found any benefit from using the augmented BFM when compared to HyperCVAD. In our experience, the outcomes with HyperCVAD are poor in this group. In this report, the treatment with PIR was associated with a higher CR rate, lower relapse rate and better OS when compared with our historical HyperCVAD in AYA-patients. The benefit on survival was independent of other risk factors or alloHSCT. The main limitation of the study is the comparison with a historical group. However, given the general trend to treat these patients with RIP, a prospective randomized study in this regard is unlikely.





Juan Rangel-Patiño, et al. 

Conclusion cited from the abstract: 

Mexican patients treated with a modified CALGB 10403 protocol had similar response rates than reported in the original protocol but with more toxicity, mainly hepatic and metabolic. However, induction-related mortality was low and we had no treatment-related toxicity after induction. We presume that the high-rate of toxicities can be related with the genetic and environmental metabolic risk factors plenty described in our population. The modified CALGB showed encouraging results in this Hispanic population, hence we have to explore lower dose schedule based in patient characteristics and asparaginase levels.