- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Opdivo (nivolumab) / Ono Pharma, BMS, Yervoy (ipilimumab) / Ono Pharma, BMS
Trial suspension, Combination therapy, Checkpoint inhibition, IO biomarker: NCI-2016-01300: Blinatumomab and Nivolumab With or Without Ipilimumab in Treating Patients With Poor-Risk Relapsed or Refractory CD19+ Precursor B-Lymphoblastic Leukemia (clinicaltrials.gov) - Dec 21, 2022 P1, N=30, Suspended, Recruiting --> Suspended Recruiting --> Suspended
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Besponsa (inotuzumab ozogamicin) / Pfizer, UCB
Trial completion date, Trial primary completion date: NCI-2017-00596: Blinatumomab, Inotuzumab Ozogamicin, and Combination Chemotherapy as Frontline Therapy in Treating Patients With B Acute Lymphoblastic Leukemia (clinicaltrials.gov) - Dec 21, 2022 P2, N=80, Recruiting, Recruiting --> Suspended Trial completion date: Nov 2021 --> Nov 2023 | Trial primary completion date: Nov 2021 --> Nov 2023
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Journal, IO biomarker: PAX5 epigenetically orchestrates CD58 transcription and modulates blinatumomab response in acute lymphoblastic leukemia. (Pubmed Central) - Dec 16, 2022 We described a PAX5-driven enhancer at the CD58 locus, which was disrupted by PAX5 P80R, and the loss of CD58 abolished blinatumomab-induced T cell activation with global changes in transcriptomic/epigenomic program. In conclusion, we identified previously unidentified genetic mechanisms of blinatumomab resistance in B-ALL, suggesting strategies for genomics-guided treatment individualization.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Review, Journal, Residual disease, IO biomarker: Measurable residual disease in acute lymphoblastic leukemia: How low is low enough? (Pubmed Central) - Dec 16, 2022 Emerging data suggest these higher sensitivity methods are superior for identifying patients at lowest risk for relapse, but it remains controversial whether to institute therapies such as blinatumomab or chimeric antigen receptor (CAR)-T cells or move patients to allogeneic hematopoietic cell transplant (alloHCT) when they have quantifiable disease burden less than 10. With additional evidence to facilitate integration of highly sensitive MRD quantification into clinical care and to contextualize MRD within the genotype of individual patients, it will likely be increasingly possible to identify patients able to avoid alloHCT and potentially even de-escalate therapy.
- |||||||||| obecabtagene autoleucel (AUTO1) / Autolus
Long-Term Follow-up of AUTO1, a Fast-Off Rate CD19 CAR, in Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia and Factors Associated with Durable Response. () - Dec 16, 2022 - Abstract #TCTASTCTCIBMTR2023TCT_ASTCT_CIBMTR_906; P1 METHODS Subjects ≥ 16y received fludarabine (30mg/m 2 x3) and cyclophosphamide (60mg/kg x1) followed by split dose AUTO1 (day 0: ≥20% Bone Marrow (BM) blasts, AUTO1 dose=10 x10 6 ; <20% BM blasts, AUTO1 dose=100 x10 6...RESULTS 20 adult B-ALL patients (median age, 41.5y), previously treated with blinatumomab (25%), inotuzumab ozogamicin (50%) and allogeneic stem cell transplantation (65%), were infused with AUTO1...This suggests that CAR-T persistence and B cell aplasia (denoting functional persistence) are associated with long-term clinical responses. We will present further analysis of factors associated with response and relapse at the conference.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis
Clinical Practice Patterns and Factors Driving Usage of Consolidative Stem Cell Transplantation Post-Tisagenlecleucel () - Dec 16, 2022 - Abstract #TCTASTCTCIBMTR2023TCT_ASTCT_CIBMTR_895; In this survey of 22 tisagenlecleucel-prescribers, over half of respondents indicated that the decision to recommend cHSCT post-tisagenlecleucel was patient-dependent. Increased disease burden pre-infusion, extramedullary disease, KMT2Ar, and history of treatment-refractoriness were associated with increased likelihood of recommending cHSCT, while having a history of HSCT, not being a TBI candidate, and Trisomy 21 were associated with decreased likelihood of recommending cHSCT.
- |||||||||| cyclophosphamide / Generic mfg.
Anaphylaxis to Cyclophosphamide Metabolites during Lymphodepletion for CAR-T Therapy () - Dec 16, 2022 - Abstract #TCTASTCTCIBMTR2023TCT_ASTCT_CIBMTR_819; Case description: A 13 year old boy was diagnosed with very high risk ALL in 2015 and had 2 isolated CNS relapses treated with intensified chemotherapy (chemo) and cranial radiation (1 st relapse) and Blinatumomab with intrathecal (IT) chemo followed by sibling donor HSCT (2 nd relapse)...Later, during lymphodepletion with fludarabine (Flu) and Cy, physiologic replacement hydrocortisone (HC) was briefly held to prevent interference with CAR-T function...CAR-T infusion was subsequently delayed by skin GVHD requiring glucocorticoids and COVID-19 infection treated with convalescent plasma and nirmatrelvir/ritonavir...Onset of anaphylaxis within hours rather than minutes after Cy administration supports hypersensitivity to Cy metabolites rather than to the drug itself. This case highlights the importance of consideration of sensitivity to Cy metabolites as well as acquired donor-specific allergy even when alternative explanations are likely.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Besponsa (inotuzumab ozogamicin) / Pfizer, UCB
Phase I Trial of CAR T-Cell Therapy Using a Fully Human CD19-Targeted Binder for Adults with Relapsed/Refractory B-ALL () - Dec 16, 2022 - Abstract #TCTASTCTCIBMTR2023TCT_ASTCT_CIBMTR_725; P1 Pts were treated with cyclophosphamide 300 mg/m 2 /d and fludarabine 30 mg/m 2 /d for 3 days followed by infusion of JCAR021 for R/R B-cell malignancies (NCT03103971) on 1 of 2 cohorts: high marrow burden ALL (HMB; > 5% bone marrow [BM] blasts; n=12); low marrow burden ALL (LMB; ≤ 5% BM; n=11)...Thirteen (57%) had received blinatumomab; 12 (52%) had received inotuzumab ozogamicin...CD19 CAR T cells with a fully human scFv for R/R adult B-ALL led to high rates of MRD-negative marrow and EM responses, but durable responses in the absence of consolidative allo-HCT were only observed in 3 pts. Additional strategies are needed to improve CAR T-cell persistence and outcomes of CD19 CAR T-cell therapy for adult R/R B-ALL.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Late-breaking abstract: Congrats to the E1910 study team led by @MRLitzow @SelinaLugerMD Ryan Mattison, MD, Zhuoxin Sun, PhD, @MartinTallman, Matthew Wieduwilt, MD, Michaela Liedtke, MD, Julie Bergeron, MD. Late-breaking abstract today at #ASH22 #leusm Frontline blinatumomab in Adult ALL #leukemia (Twitter) - Dec 13, 2022
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka, Incyte, Blincyto (blinatumomab) / Astellas, Amgen
Clinical, P2 data, Next-generation sequencing, Minimal residual disease: CONGRESS| #ASH22 @NicholasShortMD, @MDAndersonNews presents the phase II sub-study results of ponatinib + blinatumomab in pts with ND Ph+ ALL(n=40). It was well tolerated with high rates of CMR(87%) and NGS MRD negativity(88%), and estimated 2-year OS of 95% #allsm #leusm (Twitter) - Dec 10, 2022
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka, Incyte, Blincyto (blinatumomab) / Astellas, Amgen, Tasigna (nilotinib) / Novartis, Inhibikase
Review, Journal: Evidence-Based Minireview: What is the optimal tyrosine kinase inhibitor for adults with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia? (Pubmed Central) - Dec 10, 2022 While randomized data to support the TKI selection in Ph-positive ALL are lacking, data from single-arm studies suggest deeper molecular responses and superior survival outcomes with each successive generation of TKI. More recently, chemotherapy-free regimens with blinatumomab and TKIs have shown excellent results in the frontline setting and may represent an emerging paradigm shift in the treatment of Ph-positive ALL.
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