New stratification and treatment approaches in ALL - including CAR T Cell therapy
Sabina Chiaretti, Renato Bassan, Antonella Vitale, Loredana Elia, et al.
Conclusion: This is 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. Though preliminary, the rates of molecular responses and survival are highly promising.
Stephan Grupp, Shannon Maude, Andre Baruchel, Theodore W. Laetsch, et al.
Conclusion: In pts with HR cytogenetic abnormalities with historically poor prognosis, tisagenlecleucel appears effective, with high rates of durable responses, prolonged survival, and a manageable safety profile.
Nicola Goekbuget, Hervé Dombret, Gerhard Zugmaier, Massimiliano Bonifacio, et al.
Conclusion: In the final, 5-year follow-up analysis of a multinational study of adults with BCP-ALL in hematologic complete remission with MRD, median OS was 36.5 months after blinatumomab treatment. Median OS was not reached among patients with a complete MRD response in cycle 1 of blinatumomab treatment. These results provide further support for long-term OS benefits associated with blinatumomab treatment in adults with BCP-ALL and MRD.
Anna Candoni, Davide Lazzarotto, Antonio Curti, Felicetto Ferrara, et al.
Conclusion: This is one of the largest cohort of adult patients with relapsed or refractory T-ALL/T-LBL treated in real-world with Nelarabine. Taking into account the poor prognosis of this population Nelarabine can be considered as an effective option providing an ORR of 50% and a CR rate of 36%. In addition, 40% of cases who received Nelarabine salvage therapy underwent an Allo-SCT with an expected OS at 2 and 5 years of 46% and 38%, respectively. Overall, the safety profile of Nelarabine was acceptable with only 8 % of cases with grade III-IV neurological AE.
Anthony Moorman, Amy Kirkwood, Amir Enshaei, Laura Clifton-Hadley, et al.
Conclusion: PIUKALL, which was developed and validated using paediatric ALL data, is a valid and powerful biomarker in adult ALL. This intriguing observation highlights the benefit of integrating risk factors as continuous variables. We have demonstrated how PIUKALL could be used to provide additional prognostic information in treatment scenarios previously allocated by binary decision. We plan to use this risk score when designing our next adult ALL trial, UKALL15.
Choice of Poster Presentations
Dragana Slavkovic Lukic, Johannes Duell, Jan Davidson-Moncada, Andreas Schlagowsky, et al.
COMBINATION OF FLOTETUZUMAB, A CD123 X CD3 BISPECIFIC DART® MOLECULE, AND BLINATUMOMAB, A CD19 X CD3 BITE MOLECULE, TO PREVENT ANTIGEN ESCAPE IN B-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIAB-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA
Conclusion: Our results indicate that dual targeting of CD123 and CD19 with combination of low doses of flotetuzumab and blinatumomab is an attractive approach to prevent antigen escape of BCP-ALL, resulting in significant reduction of cytokine production by effector cells.
Veerle Mondelaers, Tim Lammens, Laurence Dedeken, Anne Uyttebroeck, et al.
Conclusion: This prospective nation-wide, multi-center study shows that monitoring of ASNase activity during treatment of children with ALL and NHL is feasible and informative. Allergy and SI occurred after both peg-ASNase and Erwinia ASNase administration.
Soumika Sengupta, Mainak Biswas, Khushboo Gandhi, Vikram Gota, Avinash Sonawane
Conclusion: Considering all parameters, Mutant B was found to have the most favorable characteristics and emerged as the lead candidate for future development. This formulation is expected to overcome the existing deficiencies and clinical challenges encountered with the EcA formulations. Clinical development of this drug candidate is envisaged.
Paroni Fan, Kathy Chan, Terry Chow, Grace Lam, Frankie Cheng, Chi-kong Li
Conclusion: Our results high incidence of allergy to Leunase in Chinese children. Patients allergic to Leunase were either clinically hypersensitive or silently inactivated to Oncaspar, suggesting that Oncaspar may not be a suitable alternative after Leunase allergy while the two brands of Erwinia asparaginase displayed satisfactory efficacy without triggering much hypersensitive response. Given the specificity and sensitivity, measurement of asparaginase activity should be part of the clinical monitoring to ensure adequate efficacy of different preparations.
Matthias Stelljes, Elias Jabbour, Anjali Advani, Daniel J DeAngelo, et al.
Conclusion: Improved outcomes were seen with InO vs SC among S1 pts who had a long first complete remission (CR1 ≥ 12 mos or CR1 ≥ 18 mos), supporting the benefit of InO vs SC in this population.
David I Marks, Daniel J DeAngelo, Elias Jabbour, Anjali Advani, et al.
Conclusion: These results are in agreement with current recommendations that patients proceeding to SCT should receive ≤2 Cyc, whereas those not proceeding to SCT may benefit from receiving up to 6 cycles of therapy.
Elias Jabbour, Matthias Stelljes, Anjali Advani, Daniel J DeAngelo, et al.
TIME FROM RANDOMIZATION TO FIRST SUBSEQUENT INDUCTION/SALVAGE THERAPY IN PATIENTS WITH RELAPSED/REFRACTORY ACUTE LYMPHOBLASTIC LEUKEMIA TREATED WITH INOTUZUMAB OZOGAMICIN IN THE PHASE 3 INO-VATE TRIAL
Conclusion: In this study, treatment with InO provided the benefit of extended TST, effectively allowing patients a longer time period until an ST was needed in both patients who proceeded to as well as those who did not proceed to HSCT.
Marie Emilie Dourthe, Aurélie Cabannes-Hamy, Karima Yakouben, Florence Fabian, et al.
Conclusion: CTL019 confirms its efficacy in a cohort of patients heavily pretreated for refractory or relapsed B-ALL without additional therapy after remission. The toxicity profile underlines the need of a strong collaboration between intensivists, neurologists and hematologists to successfully manage these patients.
Bijal D. Shah, Michael R. Bishop, Olalekan O. Oluwole, Aaron C. Logan, et al.
Conclusion: KTE-X19 dosing and safety management have been successfully refined by testing 3 cell doses and evaluating a new AE management guideline with altered corticosteroids/tocilizumab use for NEs/CRS. The pivotal Phase 2 portion of ZUMA-3 is ongoing at the 1 × 106 dose with revised AE management.
Jia Chen, Xiang Zhang, Yi Fan, Aining Sun, et al.
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.
Heng Mei, Yu Hu, Huiwen Jiang, Fen Zhou, et al.
Conclusion: These data demonstrate that CAR-T therapy bridging to allo-HSCT is a safe and effective therapeutic strategy for r/r B-ALL patients, and can achieve better efficacy in terms of maintaining long-term EFS and RFS. Patients with high pre-infusion MRD or with poor prognostic markers can benefit from the early consolidative allo-HSCT after CAR-T therapy. Trials were registered at www.clinicaltrials.gov as # NCT02965092 and # NCT03366350.
Huiwen Jiang, Heng Mei, Yu Hu, Tao Guo, et al.
Conclusion: To conclude, coagulation disorders frequently happen during CAR-T therapy. TF and PECAM-1 are of great importance in the etiology and pathogenesis of coagulation problems. Early and proper interventions targeted at CRS-related coagulopathy contribute a lot to the control of side effects in CAR-T therapy. This trial was registered at www.clinicaltrials.gov as # NCT02965092.