- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka, Incyte, Blincyto (blinatumomab) / Astellas, Amgen
Journal: Ph+ ALL in 2022: is there an optimal approach? (Pubmed Central) - Dec 10, 2022 With improvements in TKI efficacy and allogeneic hematopoietic cell transplantation (HCT), survival has improved over the past 3 decades, and the role of chemotherapy and allogeneic HCT is now changing. Better risk stratification, the application of the third-generation TKI ponatinib, and the use of immunotherapy with the CD19-CD3 bifunctional T-cell engaging antibody blinatumomab in place of chemotherapy has made therapy for Ph+ ALL more tolerable and arguably more efficacious, especially for older patients who comprise most patients with Ph+ ALL.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Blincyto (blinatumomab) / Astellas, Amgen
Journal, IO biomarker: Updates in infant acute lymphoblastic leukemia and the potential for targeted therapy. (Pubmed Central) - Dec 10, 2022 In contrast, infants with KMT2A-germline ALL have demonstrated excellent survival outcomes with current therapy, but there remains a high burden of treatment-related morbidity. Greater understanding of the underlying blast genetics for infants with KMT2A-germline ALL and incorporation of immunotherapeutic approaches may enable a reduction in the intensity of chemotherapy while maintaining the excellent outcomes.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Besponsa (inotuzumab ozogamicin) / Pfizer, UCB, Rituxan (rituximab) / Biogen, Zenyaku Holdings, Roche
New P2 trial: Study of Pedi-cRIB: Mini-Hyper-CVD With Condensed Rituximab, Inotuzumab Ozogamicin and Blinatumomab (cRIB) for Relapsed Therapy for Pediatric With B-Cell Lineage Acute Lymphocytic Leukemia (clinicaltrials.gov) - Dec 9, 2022 P2, N=27, Not yet recruiting,
- |||||||||| Scemblix (asciminib) / Novartis, Blincyto (blinatumomab) / Astellas, Amgen
Enrollment closed, Combination therapy: ABL001 + Dasatinib + Prednisone + Blinatumomab in BCR-ABL+ B-ALL or CML (clinicaltrials.gov) - Dec 6, 2022 P1, N=34, Active, not recruiting, Greater understanding of the underlying blast genetics for infants with KMT2A-germline ALL and incorporation of immunotherapeutic approaches may enable a reduction in the intensity of chemotherapy while maintaining the excellent outcomes. Recruiting --> Active, not recruiting
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Besponsa (inotuzumab ozogamicin) / Pfizer, UCB
Journal, Residual disease, IO biomarker: Measurable residual disease in acute lymphoblastic leukemia: methods and clinical context in adult patients. (Pubmed Central) - Dec 2, 2022 However, new approaches to target MRD in patients with T-ALL remain an unmet need. As our MRD detection assays become more sensitive and expanding novel therapeutics enter clinical development, the future of ALL therapy will increasingly utilize MRD as a criterion to either intensify or modify therapy to prevent relapse or de-escalate therapy to reduce treatment-related morbidity and mortality.
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka, Incyte, Blincyto (blinatumomab) / Astellas, Amgen
Journal: De novo lymphoid blastic phase chronic myeloid leukemia: report and contemporary discussion. (Pubmed Central) - Dec 1, 2022 De novo lymphoid blastic-phase CML can therefore be difficult to differentiate from Philadelphia positive B-ALL due to their overlapping clinical and laboratory picture, implying the need to do myeloid compartment evaluation at the time of diagnosis. With recent progress in the treatment of Philadelphia positive B-ALL, including the role of transplant with the use of novel agents, a better characterization of this disease entity in retrospective and prospective trials is warranted.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Haematopoietic Progenitor Cell Mobilisation Following Blinatumomab Therapy () - Nov 29, 2022 - Abstract #ASH2022ASH_7834; However, these patients are at risk of failed mobilisation and may benefit from pre-emptive strategies such as the use of plerixafor to optimise mobilisation success. Our relatively high rate of salvage reinfusion of autologous HPCs in ALL patients underlines the utility of universal back-up harvests for patients undergoing unrelated donor transplant.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Minimal Residual Disease Negativity after Blinatumomab Is Predictive of Survival in B-Cell Acute Lymphoblastic Leukemia: Data from a Real-Life Study () - Nov 29, 2022 - Abstract #ASH2022ASH_7332; Twenty-nine (87 %) patients received levetiracetam for seizure-prophylaxis.MRD was measured after each cycle by RT-qPCR with a sensitivity of 10-4 for clonal IgH and for BCR-ABL.As MRD response was considered clonal IgH or BCR-ABL < 10-4.Relapse-free survival (RFS) and overall survival (OS) were estimated by the Kaplan-Meier analysis and compared by the log-rank across the sub-groups using 95 % confidence intervals...MRD-responsive gain a significant survival advantage over non-responsive patients. This advantage was observed both for transplanted and non-transplanted patients.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
T-Cell Lymphocyte Kinetics As a Predictive Biomarker of Blinatumomab MRD Response in ALL-B Patients: A Single-Center Prospective Study () - Nov 29, 2022 - Abstract #ASH2022ASH_7328; By comparing the results according to disease-response (responders vs non-responders) the mean T1/T0 ratios were, respectively, 2.56 vs 1.51 for T4-eff (p = 0.008), 2.54 vs 1.67 for T8-eff (p = 0.016), 3.88 vs 1.09 for T4 IFNγ (p = 0.03), 2.89 vs 1.02 for T8 IFNγ (p = 0.03) (figure 1).CONCLUSIONPreliminary results evidence plausible association between T lymphocyte kinetics, including Inf-gamma production, and achievement of MRD negativity following the first blinatumomab cycle. Further studies with a larger population are needed to predict treatment response.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Besponsa (inotuzumab ozogamicin) / Pfizer, UCB
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: Updated Results and Predictors for Outcomes () - Nov 29, 2022 - Abstract #ASH2022ASH_7239; Pts received mini-hyper-CVD (cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, cytarabine at 0.5 g/m2 x 4 doses) for up to 8 cycles...Rituximab (if CD20+) and prophylactic IT chemotherapy were given for the first 4 cycles...Despite the reduced intensity of this regimen, a substantial proportion of pts >70 years of age died in remission. Ongoing efforts are evaluated for INO and blinatumomab without chemotherapy for these pts.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Improved Survival of Adolescents and Young Adults (AYA) Patients Aged 14-40 Years with First Relapse of Acute Lymphoblastic Leukemia Using Pediatric-Inspired Chemotherapy Salvage Protocol (R3 induction protocol) () - Nov 29, 2022 - Abstract #ASH2022ASH_7237; Background : Although survival of adolescent and young adults (AYA) with acute lymphoblastic leukemia (ALL) has improved using pediatric-inspired protocols, the outcomes of those who relapse remain poor using adult chemotherapy salvage-regimens that have historically incorporated high dose Ara-C based regimen, with long term-survival of less than 10%...The protocol consisted of vincristine (1.5mg/m2 IV D3,10,17,24); mitoxantrone ( 10mg/m2 IV d1 &2); PEG-asparaginase (1000 u/m2 IV d3 & 17); dexamethasone (10mg/m2 BID day d1-5 and d15-20); and intrathecal methotrexate (12mg d1 & d8) were identified...MRD-positive patients received blinatumomab followed by a transplant.Result s :The median age at relapse was 16 years (14-40 years), 88.2% of patients were B-cell ALL and 11.8% were T-cell ALL...At a median follow up of 4 years, OS was 47.3%.Conclusion :Compared to traditional adult-based chemotherapy regimens and antibody therapies used in relapsed ALL, the use of pediatric-inspired protocol (R3) in relapsed AYA-ALL patients showed favorable response rates and overall survival. Further trials are required of pediatric inspired salvage regimens, preferably incorporating antibody therapies in adult patients, especially in 1st relapse.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Synribo (omacetaxine mepesuccinate) / Teva
Homoharringtonine Is Effective in Treating T-ALL By Downregulating MCL-1 with Synergistic Effect When Combining with Venetoclax () - Nov 29, 2022 - Abstract #ASH2022ASH_7173; Moreover, the underlying mechanism of MCL-1 downregulation upon HHT treatment in triggering apoptosis needs further exploration. Nevertheless, our study provides a solid ground work of establishing the role of HHT and its combination with venetoclax in treating T-ALL.Acknowledgements: The work was supported by Health and Medical Research Fund (Project No: 07182526).
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Journal, CAR T-Cell Therapy: Blinatumomab Prior to CAR-T Cell Therapy-A Treatment Option Worth Consideration for High Disease Burden. (Pubmed Central) - Nov 27, 2022 To conclude, blinatumomab can effectively lower disease burden with fewer side effects than standard chemotherapeutics. Therefore, it may be a valid option for patients with high-disease burden prior to CAR-T cell therapy without clear evidence of compromising efficacy; however, further investigations are necessary.
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka, Incyte, Blincyto (blinatumomab) / Astellas, Amgen
P2 data, Journal: Ponatinib and blinatumomab for Philadelphia chromosome-positive acute lymphoblastic leukaemia: a US, single-centre, single-arm, phase 2 trial. (Pubmed Central) - Nov 20, 2022 P2 The chemotherapy-free combination of ponatinib and blinatumomab resulted in high rates of complete molecular response in patients with newly diagnosed and relapsed or refractory Ph-positive acute lymphoblastic leukaemia. Patients with newly diagnosed Ph-positive acute lymphoblastic leukaemia could be spared the toxicities associated with chemotherapy and the need for allogeneic haematopoietic stem-cell transplantation in first response.
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