- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Review, Journal: Evaluating Blinatumomab for the Treatment of Relapsed/Refractory ALL: Design, Development, and Place in Therapy. (Pubmed Central) - Nov 14, 2020 Although blinatumomab has changed the therapeutic landscape for adults with R/R B-ALL, a number of important clinical considerations and questions remain, including the potential role of blinatumomab in the frontline setting, mechanisms of resistance, optimal goal MRD level, the role of transplant following MRD clearance, the optimal place for blinatumomab in the context of other recently approved immune-mediated therapies, and real world outcomes for patients treated outside the context of clinical trials. These issues are the focus of ongoing studies, which will hopefully inform future clinical practice regarding the utility of blinatumomab in the treatment of B-ALL patients.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Clinical, Clinical Trial,Phase II, Journal, IO biomarker: Dasatinib-Blinatumomab for Ph-Positive Acute Lymphoblastic Leukemia in Adults. (Pubmed Central) - Nov 6, 2020 P2 A chemotherapy-free induction and consolidation first-line treatment with dasatinib and blinatumomab that was based on a targeted and immunotherapeutic strategy was associated with high incidences of molecular response and survival and few toxic effects of grade 3 or higher in adults with Ph-positive ALL. (Funded by Associazione Italiana per la Ricerca sul Cancro and others; GIMEMA LAL2116 D-ALBA EudraCT number, 2016-001083-11; ClinicalTrials.gov number, NCT02744768.).
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
[VIRTUAL] Predictive Model of Response to Blinatumomab Therapy in Children and Adults with Relapsed/Refractory B-ALL () - Nov 5, 2020 - Abstract #ASH2020ASH_4999; Based on the model high probability of response in case of short time to next line of therapy is observed only for adult patients with low-to-moderate blast count, while in patients with long time to next line of therapy broader patient population has a high probability of response, including young children and patients with high blast count. Verification of this model in a larger multicenter study is required to confirm this hypothesis.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
[VIRTUAL] Phase II Study of Blinatumomab and Concurrent Oral Tyrosine Kinase Inhibitor Therapy As Consolidation and Maintenance Therapy for Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Following Chemotherapy-Sparing Induction (Poster Hall (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_3637; P2 Others have previously reported rates of morphologic complete response (mCR) approaching 100% among adults w/ Ph+ ALL treated w/ corticosteroids (CS) and dasatinib (DAS) alone as induction therapy, but w/ low rates of minimal residual disease (MRD) negativity by flow cytometry (FACS) and BCR-ABL1 PCR (complete molecular response, CMR) and high rates of relapse in the absence of further consolidation.The bispecific T-cell engager blinatumomab (BLIN) has considerable efficacy in clearing MRD in patients (pts) w/ Ph- B-cell ALL...The ongoing D-ALBA study (GIMEMA LAL2116) is also investigating BLIN + DAS consolidation following 12 weeks of induction (prednisone + DAS followed by DAS), w/out protocol-specified maintenance, and has demonstrated preliminary evidence of efficacy (Chiaretti et al., ASH Meeting, 2019)...Pts are eligible if they are ≥18 years-old w/ Ph+ ALL confirmed by cytogenetic or molecular studies, ECOG performance status 0-2, w/out prior therapy for ALL beyond CS, hydroxyurea, or intrathecal chemotherapy, w/out known active extramedullary disease and/or CNS-3 disease, and w/ appropriate organ function.See Figure 1: pts will receive a CS pre-phase (days [d] -6 – 0) followed by modified GIMEMA LAL1205 induction (dexamethasone [DEX] 10 mg/m2 [max 24 mg/d], d1-24, tapered off d25-32) + DAS 140 mg/d (dose adjustments or TKI change permitted per protocol) w/ intrathecal methotrexate (IT MTX) d22, 43 and bone marrow (BM) assessments including FACS and BCR-ABL1 PCR...If ≥ 3 of the first 10 pts achieve CMR we will continue enrollment to max 17 pts. If ≥ 6 pts achieve CMR, then BLIN + TKI will be considered promising for further investigation.The investigators are hopeful this study will add to the currently limited prospective data supporting TKI + BLIN consolidation/maintenance for pts w/ Ph+ ALL and efforts to develop chemotherapy-sparing and immunotherapeutic strategies for older pts w/ ALL.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Iclusig (ponatinib) / Takeda, Otsuka, Incyte, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
[VIRTUAL] Interim Results of the Phase I/II Study of the Ponatinib, Venetoclax and Dexamethasone for Patients with Relapsed or Refractory Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Channel 19 (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_3192; The chemotherapy-free, oral combination of ponatinib, venetoclax and dexamethasone appears safe and has promising early efficacy in this heavily pretreated population of pts with R/R Ph+ ALL, with all 3 pts who received venetoclax 800mg daily achieving CMR. The MTD has not yet been reached, and the study continues to accrue.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Arranon (nelarabine) / Novartis, Besponsa (inotuzumab ozogamicin) / Pfizer, UCB
[VIRTUAL] Evaluating Outcomes of Adult Patients with Acute Lymphoblastic Leukemia Treated on the GMALL Protocol (Poster Hall (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_1962; Conclusions While results are improving for patients treated on GMALL, a substantial patient segment still experiences relapse. It is conceivable that in the near future new novel therapeutic modalities for adult ALL involving the use of monoclonal antibodies and CAR-T cell therapy will help reduce relapse rates and further improve the current outcomes of patients treated on the GMALL protocol.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
[VIRTUAL] Superior Event-Free Survival with Blinatumomab Versus Chemotherapy in Children with High-Risk First Relapse of B-Cell Precursor Acute Lymphoblastic Leukemia: A Randomized, Controlled Phase 3 Trial (Channel 19 (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_1609; Children with M1 (< 5% blasts) or M2 (< 25% and ≥ 5% blasts) marrow were randomized 1:1 after induction therapy and cycles of HC1 and HC2 chemotherapy, administered according to the IntReALL HR 2010, ALL-REZ BFM 2002, ALL R3, COOPRALL, and AIEOP ALL REC 2003 protocols, to receive a third consolidation course with blinatumomab (15 µg/m2/day for 4 weeks) or HC3 (dexamethasone, vincristine, daunorubicin, methotrexate, ifosfamide, PEG-asparaginase); intrathecal chemotherapy (methotrexate/cytarabine/prednisolone) was administered before treatment. Blinatumomab monotherapy as consolidation therapy before alloHSCT in children with HR first-relapse BCP-ALL leads to significantly better EFS, lower risk of recurrence, and fewer grade ≥ 3 treatment-emergent AEs vs HC3, suggesting a new standard‑of-care treatment for these patients.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Besponsa (inotuzumab ozogamicin) / Pfizer, UCB, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
[VIRTUAL] Reduced-Intensity Chemotherapy with Mini-Hyper-CVD Plus Inotuzumab Ozogamicin, with or without Blinatumomab, in Older Adults with Newly Diagnosed Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia: Results from a Phase II Study (Poster Hall (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_772; This novel regimen leads to durable remissions and apparent cure in the majority of pts age 60-69 years of age and in those without poor-risk cytogenetic features. To decrease treatment-related mortality, the protocol has been amended to eliminate chemotherapy for pts ≥70 years of age.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Besponsa (inotuzumab ozogamicin) / Pfizer, UCB
Clinical, Review, Journal: Immunotherapy in Pediatric B-Cell Acute Lymphoblastic Leukemia: Advances and Ongoing Challenges. (Pubmed Central) - Nov 3, 2020 In this article, we discuss the clinical biology and treatment of B-ALL with an emphasis on the role of immunotherapy in overcoming the challenges of conventional cytotoxic therapy. As immunotherapy continues to move into the frontline of pediatric B-ALL therapy, we also discuss strategies to address unique side effects associated with these agents and efforts to overcome mechanisms of resistance to immunotherapy.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Opdivo (nivolumab) / Ono Pharma, BMS
[VIRTUAL] Validation of the Combinatorial Effect of Blinatumomab and Nivolumab in Cancer Therapy (virtual poster hall) - Nov 3, 2020 - Abstract #SITC2020SITC_2044; Finally, we have employed humanized mouse models bearing Raji or Daudi tumor cells to further validate this combination treatment in vivo. Both In-vivo and In-vitro data support that Blinatumomab is dominant in activing T cell and Nivolumab can only exhibit synergistic effect under suboptimal dosage of Blinatumomab.Download figure Open in new tab Download powerpoint Abstract 781 Figure 1 Establishment of In vitro co-culture system for CD3 BiTEestablish in vitro human PBMC based system to validate CD3 BiTE functionDownload figure Open in new tab Download powerpoint Abstract 781 Figure 2 Opdivo and CD3 BiTE CombinationOpdivo could further promote T cell activation under the treatment of CD3 BiTE Conclusions Successfully establish in vitro system to evaluate the function of CD3 BiTE and also take advantage of MLR/tumor co-culture system to demonstrate PD1 antibody could further promote T cell activation under appropriate dosage of CD3 BiTE.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Opdivo (nivolumab) / Ono Pharma, BMS
[VIRTUAL] Validation of the Combinatorial Effect of Blinatumomab and Nivolumab in Cancer Therapy (virtual poster hall) - Nov 3, 2020 - Abstract #SITC2020SITC_1947; Finally, we have employed humanized mouse models bearing Raji or Daudi tumor cells to further validate this combination treatment in vivo. Both In-vivo and In-vitro data support that Blinatumomab is dominant in activing T cell and Nivolumab can only exhibit synergistic effect under suboptimal dosage of Blinatumomab.Download figure Open in new tab Download powerpoint Abstract 781 Figure 1 Establishment of In vitro co-culture system for CD3 BiTEestablish in vitro human PBMC based system to validate CD3 BiTE functionDownload figure Open in new tab Download powerpoint Abstract 781 Figure 2 Opdivo and CD3 BiTE CombinationOpdivo could further promote T cell activation under the treatment of CD3 BiTE Conclusions Successfully establish in vitro system to evaluate the function of CD3 BiTE and also take advantage of MLR/tumor co-culture system to demonstrate PD1 antibody could further promote T cell activation under appropriate dosage of CD3 BiTE.
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[VIRTUAL] Update on chimeric antigen receptor – T cells (CAR-T) CD19 therapy: the Sheba experience () - Oct 31, 2020 - Abstract #EHOC2020EHOC_327; Lympho-depleting conditioning was inducted by fludarabine 25 mg/m2 for 3 days and cyclophosphamide 900 mg/m2 for 1 day, followed by infusion of 1–1.5 × 106 transduced CAR-T cells per kilogram weight...Ten of 37 (27%) ALL patients received prior therapy directed against CD19, such as blinatumomab and Inotuzumab...The manufactured CAR-T products (n = 9) were also subjected to immunophenotypic analysis in order to elucidate the mechanisms of CAR-T cell trafficking and activity. We observed increased immunosuppressive phenotype as well as induction of T cell senescence/exhaustion in non-responding compare to responding patients.4
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Besponsa (inotuzumab ozogamicin) / Pfizer, UCB
Review, Journal, Adverse events: Management of adverse effects of new monoclonal antibody treatments in acute lymphoblastic leukemia. (Pubmed Central) - Oct 30, 2020 Although these novel immunotherapies have revolutionized the therapeutic landscape, it is important to understand the crucial aspects of administration, especially toxicity. In this article, we review the unique toxicities and adverse effects of blinatumomab and inotuzumab ozogamicin and provide recommendations for prevention of adverse effects as well as the management options for each medication.
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