- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Besponsa (inotuzumab ozogamicin) / Pfizer, UCB
Clinical, Journal: Antibody and cellular immunotherapies for acute lymphoblastic leukemia in adults. (Pubmed Central) - Apr 15, 2022
With indisputable activity in patients with relapsed or refractory ALL, efforts now hope to integrate these agents into earlier phases of treatment. In this review, we will discuss the available antibody and cellular-based immunotherapies for the treatment of patients with ALL and provide a clinical and biologic framework with which to inform treatment approaches.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Journal: Trispecific T-cell engagers for dual tumor-targeting of colorectal cancer. (Pubmed Central) - Apr 9, 2022
Retargeting of T lymphocytes toward cancer cells by bispecific antibodies has demonstrated its therapeutic potential, with one such antibody approved for the treatment of acute lymphoblastic leukemia (blinatumomab) and several other in clinical trials...In addition, it was less efficient at killing single-positive target cells than the corresponding bispecific controls, leading to potentially enhanced tumor specificity. Moreover, dual targeting of two tumor-associated antigens may contribute toward preventing the tumor escape by antigen loss caused by selective pressures from conventional single-targeting T-cell engagers, and may help to overcome antigenic heterogeneity.
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka, Incyte, Blincyto (blinatumomab) / Astellas, Amgen
Clinical, Review, Journal: SOHO State of the Art Updates & Next Questions: Intensive and Non-Intensive Approaches for Adults With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia. (Pubmed Central) - Apr 8, 2022
In this review, we discuss the evolving approach to the treatment of adults with newly diagnosed Ph+ ALL and the major principles that should guide therapy in this disease. We also review the rationale and data supporting the use of novel, chemotherapy-free regimens in Ph+ ALL, and how these approaches may soon become new standards of care.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Review, Journal: Bispecific immunomodulatory antibodies for cancer immunotherapy. (Pubmed Central) - Apr 2, 2022
Bispecific antibody-based immunotherapies have gained momentum in preclinical and clinical investigations following the regulatory approval of the T cell-redirecting antibody blinatumomab...Currently, there are more than 50 bispecific antibodies under clinical development for a range of indications, with promising signs of therapeutic activity. We also discuss two approaches for in vivo secretion, direct gene delivery and infusion of ex vivo gene-modified cells, which may become instrumental for the clinical application of next-generation bispecific immunomodulatory antibodies.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Preclinical, Journal: Cytofluorimetric assay to investigate variability in blinatumomab in vitro response. (Pubmed Central) - Apr 2, 2022
Whether and how this difference is affected by PAX5-regulated CD19 expression is unclear and whether it is predictive of in vivo response to therapy remains to be established. Further dedicated studies are required to investigate these issues in detail.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Besponsa (inotuzumab ozogamicin) / Pfizer, UCB
Review, Journal, Residual disease: Clinical Value of Measurable Residual Disease in Acute Lymphoblastic Leukemia. (Pubmed Central) - Mar 29, 2022
Additionally, the availability of highly effective agents for MRD eradication, such as blinatumomab, inotuzumab ozogamicin, and chimeric antigen receptor (CAR) T-cell therapies, enabled the development of frontline regimens capable of eradicating MRD early in the treatment course. While long-term follow-up of this approach is lacking, it has the potential to significantly reduce the need for intensive post-remission treatments, including allogeneic bone marrow transplantation, in a significant proportion of patients with ALL.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Opdivo (nivolumab) / Ono Pharma, BMS
Enrollment open, Combination therapy, Checkpoint inhibition: AALL1821: A Study to Compare Blinatumomab Alone to Blinatumomab With Nivolumab in Patients Diagnosed With First Relapse B-Cell Acute Lymphoblastic Leukemia (B-ALL) (clinicaltrials.gov) - Mar 29, 2022
P2, N=550, Recruiting,
While long-term follow-up of this approach is lacking, it has the potential to significantly reduce the need for intensive post-remission treatments, including allogeneic bone marrow transplantation, in a significant proportion of patients with ALL. Suspended --> Recruiting
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Enrollment closed: Observational Study of Blinatumomab (clinicaltrials.gov) - Mar 25, 2022
P=N/A, N=279, Active, not recruiting,
Suspended --> Recruiting Recruiting --> Active, not recruiting
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Journal: Platelets subvert antitumor efficacy of T cell-recruiting bispecific antibodies. (Pubmed Central) - Mar 24, 2022
P1
BsAb-mediated T-cell reactivity could be restored by platelet inhibition and specifically by blocking the TGF-β axis. Together, our findings demonstrate that platelets undermine the efficacy of T cell-recruiting bsAb and identify modulation of platelet function as a means to reinforce the effectiveness of bsAb treatment.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Preclinical, Journal, IO biomarker: Anticancer effects of a single intramuscular dose of a minicircle DNA vector expressing anti-CD3/CD20 in a xenograft mouse model. (Pubmed Central) - Mar 24, 2022
Among them, the US Food and Drug Administration (FDA)-approved blinatumomab (BLI) is very effective in eliminating the minimum residual disease (MRD) of acute lymphoblastic leukemia (ALL), resulting in long-term remission in many individuals...These results suggest that the i.m. MC technology can eliminate the physical and financial burdens of i.v. delivered BLI without compromising anticancer efficacy and that cancer can be treated as easily as injecting a vaccine. This, together with other superior MC features, such as safety and affordability, suggests that the i.m. MC BsAb technology has great clinical application potential.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Review, Journal: Development of Bispecific Antibody for Cancer Immunotherapy: Focus on T Cell Engaging Antibody. (Pubmed Central) - Mar 17, 2022
Several aspects of a new TCEB-Blinatumomab-are reviewed, including the current clinical data, challenges of patient treatment, drawbacks regarding toxicities, and resistance of TCEB therapy. Development of the next generation of TCEBs is also discussed in addition to the comparison of TCEB with current chimeric antigen receptor-T therapy.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Review, Journal: Acute Lymphoblastic Leukaemia in the Youngest: Haematopoietic Stem Cell Transplantation and Beyond. (Pubmed Central) - Mar 15, 2022
In contrast, the clinical presentations and biological features of ALL in children >1 year but <4 years often resemble those presented by older children. In this review, we explore the state of the art regarding haematopoietic stem cell transplantation (HSCT) in children <4 years, the preparative regimens available, and new developments in the field that may influence treatment decisions.
- |||||||||| cladribine / Generic mfg.
Review, Journal: The cure of leukemia through the optimist's prism. (Pubmed Central) - Mar 11, 2022
Survival in both younger and older patients with ALL has improved with the addition of antibodies targeting CD20, CD19 (blinatumomab), and CD22 (inotuzumab) to chemotherapy. Several recent drug discoveries (venetoclax, FLT3 and IDH inhibitors, and oral hypomethylating agents) are also improving outcomes for younger and older patients with AML and for those with higher risk myelodysplastic syndrome.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
IL-12 overcomes T-cell immune suppression by the B-ALL microenvironment (Section 39) - Mar 9, 2022 - Abstract #AACR2022AACR_5503;
In addition to suppressing CD44 and CD107b, we also found that B-ALL-secreted factors also suppress the activation of signaling pathways downstream of the TCR.Considering clinical implications of this discovery, we further explored IL-12 ex vivo in combination with the clinically approved bi-specific T-cell engager, blinatumomab. Notably, B-ALL-secreted factors reduced blinatumomab-mediated T-cell lysis of target cells, which was restored with recombinant IL-12 treatment.Overall, this data shows the potential for IL-12 to be used as an immunotherapeutic in conjunction with other current therapies to overcome T-cell suppression by B-ALL.
- |||||||||| S63845 / Servier, Novartis, Ligand, Blincyto (blinatumomab) / Astellas, Amgen, Koselugo (selumetinib) / Merck (MSD), AstraZeneca
Exploring the combinatorial potential of bispecific T-cell engagers in high throughput format (Section 38) - Mar 9, 2022 - Abstract #AACR2022AACR_4824;
Depending on compound combination, we observe synergistic but also antagonistic effects. Our data support the outstanding usefulness of this methodological approach for the exploration of bispecific cytotoxic immune cell engager agents.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Platelet-derived TGFβ undermines treatment efficacy of t cell recruiting bispecific antibodies (Section 37) - Mar 9, 2022 - Abstract #AACR2022AACR_4794;
P1
BsAb-mediated T cell reactivity could generally be restored by inhibiting platelets using dabigatran, but also specifically by blocking the TGFβ axis. Together, our findings unravel that platelets undermine the efficacy of T cell-recruiting bsAb and identify modulation of platelet function and TGFβ as means to reinforce the effectiveness of bsAb treatment.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Besponsa (inotuzumab ozogamicin) / Pfizer, UCB
Review, Journal: Bispecific Antibodies and Other Non-CAR Targeted Therapies and HSCT: Decreased Toxicity for Better Transplant Outcome in Paediatric ALL? (Pubmed Central) - Mar 8, 2022
Specific issues to be addressed include: (1) The use of these agents to reduce measurable residual disease (MRD) prior to HSCT and their potential for improved transplant outcomes due to reduced toxicity compared to traditional chemotherapy salvage, as well as potentially increased toxicity with HSCT with particular agents; (2) the appropriate sequencing of innovative therapies, i.e., when to use BiTEs or antibodies versus CARs pre- and/or post-HSCT; this will include also the potential for impact on response of one group of agents on response to the other; (3) the role of these agents particularly in the post-HSCT relapse setting, or as maintenance to prevent relapse in this setting; (4) special populations in which these agents may substitute for traditional chemotherapy during induction or consolidation in patients with predisposing factors for toxicity with traditional therapy (e.g., Trisomy 21, infants), or those who develop infectious complications precluding delivery of full standard-of-care (SOC) chemotherapy during induction/consolidation (e.g., fungal infections); (5) the evidence we have to date regarding the potential for substitution of blinatumomab for some of the standard chemotherapy agents used pre-HSCT in patients without the above risk factors for toxicity, but with high risk disease going into transplant, in an attempt to decrease current rates of transplant-related mortality as well as morbidity; (6) the unique toxicity profile of these agents and concerns regarding particular side effects in the HSCT context. The manuscript will include both the data we have to date regarding the above issues, ongoing studies that are trying to explore them, and suggestions for future studies to further refine our knowledge base.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Opdivo (nivolumab) / Ono Pharma, BMS, Imbruvica (ibrutinib) / AbbVie, J&J
Trial completion: Ibrutinib, Nivolumab and Blinatumomab in Richter Transformation (clinicaltrials.gov) - Mar 7, 2022
P2, N=10, Completed,
Not yet recruiting --> Recruiting Active, not recruiting --> Completed
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Anti-CD19-CAR / Beijing Doing Biomedical
Journal, IO biomarker: Factors associated with treatment response to CD19 CAR-T therapy among a large cohort of B cell acute lymphoblastic leukemia. (Pubmed Central) - Mar 1, 2022
P1, P1/2
Our data showed that TP53 mutation, bone marrow blasts > 20%, prior CAR-T/blinatumomab treatment, and severe cytokine release syndrome (CRS) were associated with a lower complete remission (CR) rate while age, extramedullary disease, complex cytogenetics, history of prior transplant, prior courses of chemotherapy, CAR-T cell dose, and manufacturing source of the cellular product did not affect patients' CR rate...Précis TP53 mutation and BM blasts > 20% are two independent factors associated with the CR rate. Patients with high tumor burden as well as those with bone marrow blasts < 5% can benefit from consolidative allo-HSCT post-CAR-T therapy.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Review, Journal: The Role of Bispecific Antibodies in Non-Hodgkin's Lymphoma: From Structure to Prospective Clinical Use. (Pubmed Central) - Mar 1, 2022
More specifically, they have elicited a great interest in the setting of non-Hodgkin's lymphoma (NHLs), where they could represent a viable option for more fragile patients or those resistant to other conventional therapies. This review aims to give a brief overview of the different available bsAb formats and their mechanisms of action, pinpointing the differences between IgG-like and non-IgG-like classes and will then focus on those in advanced clinical development for NHLs.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen
Blinatumomab: Love it or leave it? (Anaheim Convention Center - Learning Hall: Poster Pavilion) - Feb 25, 2022 - Abstract #ONS2022ONS_292;
Of the 45 patients, 43 had a complete response and went to transplant. Blinatumomab we love it!!
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