- |||||||||| imatinib / Generic mfg.
UPDATED RESULTS OF THE GIMEMA LAL2116, D-ALBA TRIAL, FOR NEWLY DIAGNOSED ADULTS WITH PH+ ALL (RED ROOM 1) - Nov 16, 2021 - Abstract #SIE2021SIE_30; To further improve the outcome of these cases, we designed an induction/consolidation chemo-free trial (GIMEMA LAL2116, D-ALBA) based on the administration of dasatinib plus steroids followed by at least two cycles of blinatumomab (maximum 5) and central nervous system (CNS) prophylaxis...Within not-transplanted patients, 29 continued treatment with a TKI: 21 continued with dasatinib alone, 3 switched to imatinib due to intolerance and 5 switched to ponatinib for a molecular increase or medical decision: in the latter group, 1 CNS relapse was observed...Finally, a low transplant-related mortality rate was recorded. Notably, among the few relapses, we observed a rather high incidence of CNS involvement; thus, in the upcoming trial, CNS prophylaxis will be increased.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Opdivo (nivolumab) / BMS, Yervoy (ipilimumab) / BMS
Trial completion date, Trial primary completion date, 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) - Nov 9, 2021 P1, N=30, Recruiting, Although the limited power of this study to detect a significant difference between subgroups is acknowledged, the data suggest that blinatumomab and InO may have comparable efficacy as a first or second NA therapy in RR ALL. Trial completion date: Nov 2021 --> Nov 2022 | Trial primary completion date: Nov 2021 --> Nov 2022
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Journal, IO biomarker: Down syndrome and acute lymphoblastic leukemia (Pubmed Central) - Nov 6, 2021 The CRLF2 abnormality is found in 30-60% of DS-ALL cases. In the future, treatment of CRLF2, targeting JAKs downstream of CRLF2, and administration of blinatumomab or CAR-T therapy will be incorporated into DS-ALL treatment.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Multidisciplinary Provider Insights to Promote Adoption of Bispecific Antibodies to Treat Cancer in the Community (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_5740; The survey primarily assessed experiences with blinatumomab, the first FDA-approved bispecific antibody for the treatment of malignancy (Newman & Benani, 2016)...With this survey data, ACCC is positioned to offer this support. Through its education program, ACCC will build on the survey results to develop content and resources that prepare multidisciplinary providers to welcome BsAbs into the community to treat cancer.
- |||||||||| Besponsa (inotuzumab ozogamicin) / Pfizer, UCB
Potential Impact of Treatment with Inotuzumab Ozogamicin on Chimeric Antigen Receptor T-Cell Therapy in Children with Relapsed or Refractory Acute Lymphoblastic Leukemia (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_5522; InO as a bridging strategy to CAR T-19 does not seem to result in inferior response when EFS/OS are compared to published data (Maude, NEJM 2018; Pasquini, Blood Adv, 2020). The ITCC/IntReALL-059 study will treat very high risk first relapsed BCP-ALL pts (very early relapse or presence of TP53 mutation and/or deletion, hypodiploidy, t (1;19)/ t (17;19), KTM2A / AF4 ) with InO reinduction followed by CART, given the poor prognosis with current strategies.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Blinatumomab for Patients with Richter’s Syndrome: A Multicenter Phase 2 Trial from the Filo Group (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_5258; P2 Considering the whole strategy (including R-CHOP debulking) (n=28), 15 (54%) patients achieved overall response including 11 (39%) CR. Conclusions Our preliminary data suggest that blinatumomab suggests encouraging anti-tumor activity and acceptable toxicity in patients with RS.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Besponsa (inotuzumab ozogamicin) / Pfizer, UCB
Age-Related Clonal Hematopoiesis Is a Precursor for Adult Acute Lymphoblastic Leukemia (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_5161; This may reflect the frequent use of antibody-based therapies (i.e. blinatumomab and inotuzumab) at diagnosis (on a clinical trial basis) or relapse in the two centers where these patients were treated. Collectively, these data suggest that ARCH may constitute a fertile soil for acute lymphoblastic leukemogenesis and further studies are warranted to interrogate the dynamic interplay between myeloid and lymphoid compartments of these patients.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Besponsa (inotuzumab ozogamicin) / Pfizer, UCB
Updated Results from a Phase II Study of Mini-Hyper-CVD Plus Inotuzumab Ozogamicin, with or without Blinatumomab, in Older Adults with Newly Diagnosed Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_5081; Even with this relatively reduced-intensity regimen, deaths in remission (usually due to infection) occur, primarily in pts ≥70 years of age. A strategy using the combination INO and blinatumomab, without any chemotherapy, is being explored in this population.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Dose Reduced Chemotherapy in Sequence with Blinatumomab for Newly Diagnosed Older Patients with B-Precursor Adult Lymphoblastic Leukemia (ALL): Results of the Ongoing GMALL Bold Trial (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_5080; After a 5-d prephase with dexamethasone (dexa) and cyclophosphamide (cyclo) pts receive dexa (10 mg/m 2 d 7-8 and 14-17), vincristine (2 mg d 7 and 14) and idarubicin (10 mg d 7 and 15) together with i.th...Rituximab is given to pts with CD20+ ALL...Consolidation treatment consists of alternating cycles of intermediate-dose methotrexate/ PEG-asparaginase, intermediate-dose cytarabine and reinduction and 3 further cycles of Blina...Age and subtype appeared to have an impact on the outcome with poorer results for older pts and those with pro-B-ALL. Confirmation of the results in a larger, potentially randomized trial and with longer follow-up is warranted.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Iclusig (ponatinib) / Takeda, Otsuka, Incyte
Venetoclax-Ponatinib for T315I/Compound-Mutated Ph+Acute Lymphoblastic Leukemia (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_5076; The outcome of Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) have greatly improved in tyrosine kinase inhibitors (TKIs) era and is just moving to a chemo-free era using dasatinib and blinatumomab (Foà R, N Engl J Med...Moreover, venetoclax had a strong synergistic effect with ponatinib and dexamethasone on inducing apoptosis of primary blast cells and BaF3 cells expressing p190 BCR/ABL with T315I-mutation in vitro , with a combination index of 0.019 when the suppressing rate is 0.05, while the effect was significant decreased when ponatinib was replaced by dasatinib (Figure 1D-F), a prominent change of mitochondrial membrane potential as well as the cleavage of PARP were also observed in triple-combination treatment group (Figure 1G-H)...A clinical trial also using similar VPD regimen for treatment of R/R Ph+ ALL is ongoing now (Short NJ, Am J Hematol . 2021).
- |||||||||| Besponsa (inotuzumab ozogamicin) / Pfizer, UCB
A Phase II Study of Inotuzumab Ozogamicin for the Treatment of Measurable Residual Disease-Positive B-Cell Acute Lymphoblastic Leukemia (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_3921; Ursodiol prophylaxis was given to all pts...Ten pts (63%) had Ph-positive ALL; 9 pts received concomitant ponatinib, and 1 received dasatinib...Nine (56%) pts had received prior blinatumomab, 3 (19%) pts had undergone prior ASCT, and one (6%) patient had undergone CAR-T...One patient discontinued study treatment due grade 3 veno-occlusive disease after 5 courses of INO. Conclusion : INO is a well-tolerated and effective agent to eradicate MRD in pts with B-cell ALL who have persistent MRD or who experience MRD recurrence.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
“My T Cell”: A Smartphone Application for Guidance of CAR T Logistics and Management of CAR T & BiTE Related Toxicities (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_3521; The Bispecific T-cell engager (BiTE) Blinatumomab and CD19-specific Chimeric Antigen Receptor (CAR) T-cell products are approved for the treatment of relapsed and refractory B-cell neoplasms...Health care professionals validated feasibility and in particular appreciated fast and easy assessment of toxicity grading and management. Thus, “myTcell” is a tool that has the potential to improve guideline adherence and accelerate broader and safer application of CARs and BiTEs based immunotherapy.
- |||||||||| Kymriah (tisagenlecleucel-T) / Novartis, Blincyto (blinatumomab) / Astellas, Amgen
Complete Versus Incomplete Hematologic Recovery after CAR T Cell Therapy: Implications for Relapse Free Survival and Overall Survival in Pediatric and Young Adult Patients with Relapsed/Refractory B-ALL (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_3331; P1, P1/2, Forty patients (39%) met criteria for CRi with both ANC <1000/µL and platelets <100,000/µL, 40 (39%) for isolated thrombocytopenia, and 20 (20%) for neutropenia alone. Median age at leukemia diagnosis was 7 years (range 0.2-24), and at CAR T cell infusion was 12 years (range 1-29), with 48% undergoing a prior allogeneic stem cell transplant (HSCT), 32% with high risk cytogenetics, and 10% with prior blinatumomab treatment, none of which differed between the CR and CRi groups (Table 1).
- |||||||||| Besponsa (inotuzumab ozogamicin) / Pfizer, UCB
Outcomes of Children and Young Adults with Acute Lymphoblastic Leukaemia Administered Inotuzumab Pre CAR-T Therapy (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_3327; InO prior to CAR T cell therapy was well tolerated despite the cohort being heavily pre-treated except for one patient who developed fatal VOD prior to CAR T cell infusion. InO was given for disease debulking, rather than to achieve MRD negativity and hence majority of the cohort (75%) received only 1 dose of InO in bridging rather than the usual schedule of three doses weekly per cycle.
- |||||||||| mirdametinib (PD-0325901) / SpringWorks Therap, BeiGene, Mekinist (trametinib) / Novartis, Blincyto (blinatumomab) / Astellas, Amgen
Modeling Relapsed, Refractory Acute Lymphoblastic Leukemia from a Child with Neurofibromatosis (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_2882; He relapsed three years later off treatment and was refractory to both salvage chemotherapy and blinatumomab...In a 3-day cell death assay, only P2RY8-CRLF2 + NF1 fs demonstrated sensitivity to trametinib (LD 50 P2RY8-CRLF2 = >6.4 µM, NF1 fs = >6.4 µM, P2RY8-CRLF2 + NF1 fs =1.7µM; p 16 µM, NF1 fs = >16 µM, P2RY8-CRLF2 + NF1 fs = 8.3 µM; p < 0.0001) (Figure 2)...An understanding of the genomic complexities that lead to relapse may also inform personalized treatment strategies. While this patient subsequently achieved remission with inotuzomab and underwent successful stem cell transplantation, the sensitivity to MEK inhibitors is an exciting development for neurofibromatosis patients with ALL.
- |||||||||| OSE-127 / Servier
IL7R Targeting Using OSE-127 Shows Robust Anti-Leukemic Activity in B-Cell Precursor Acute Lymphoblastic Leukemia Xenografts (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_2878; Of note, OSE-127 therapy response associated with IL7R expression levels on BCP-ALL cells and no significant downregulation of the IL7R antigen was observed upon OSE-127 treatment. Taken together, our data demonstrate that IL7R-targeting using OSE-127, which has already demonstrated a good safety profile in healthy volunteers, is an efficient approach for BCP-ALL immunotherapy and may be particularly beneficial for patients with high IL7R-expression and/or relapsed/refractory disease after CD19-directed therapy.
- |||||||||| T Cell Engaging Bispecific Antibodies Produce Durable Response in Mesothelin-Positive Patient-Derived Xenograft Models of Pediatric AML (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_2843;
Antibody single-chain variable region (scFv) sequences derived from amatuximab recognizing MSLN and from either blinatumomab or AMG330 targeting CD3 were used to engineer and express two MSLN/CD3-targeting BsAbs: MSLN AMA -CD3 L2K and MSLN AMA -CD3 AMG respectively...Chemotherapy (DA) consisted of 3 doses of 1.5 mg/kg daunorubicin iv and 5 doses of 50 mg/kg cytarabine ip...Conclusion These data validate the efficacy of MSLN-targeting BsAbs in PDX models with endogenous MSLN expression. Because prior MSLN-directed therapies appeared safe in humans, MSLN-targeting BsAbs could be ideal immunotherapies for MSLN-positive pediatric AML patients.
|