Blincyto (blinatumomab)

"Introduction: Brexucabtagene autoleucel (brexu cel) is a CD19-targeted chimeric antigen receptor (CAR) T cell therapy approved for the treatment of adults with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL)...No differences were observed with respect to sex, TP53 mutation status, prior inotuzumab (ino) or blinatumomab (blina) exposure, disease burden prior to CAR, or development of any cytokine release syndrome (CRS) or any neurotoxicity with brexu cel... In a large real-world cohort of adults with R/R B-ALL infused with brexu cel, we identified practice variation regarding the use of consolidative HCT. Among brexu cel recipients who entered an MRD- CR, we identified ClonoSeq NGS MRD negativity as a novel predictive factor of favorable oncologic outcomes, even without a consolidative HCT. Similar results have been obtained in pediatric ALL patietns ftreated with 41BB-based tisagenleucleucel (Pulsipher et al., Blood Cancer Discovery 2022)."

P1/2, N=35, Active, not recruiting, St. Jude Children's Research Hospital | N=98 --> 35 | Trial completion date: Jul 2029 --> Mar 2025 | Trial primary completion date: Aug 2025 --> Jun 2024

P2, N=300, Suspended, National Cancer Institute (NCI) | N=550 --> 300

This report presents two pediatric ALL cases (one Ph+ and one Ph-like) with minimal residual disease negativity established by multicolor flow cytometry but persistent transcript detection by quantitative PCR (qPCR) even after second-line treatment with tyrosine kinase inhibitors combined with blinatumomab immunotherapy. Using droplet digital PCR, BCR::ABL1 or TPM3::PDGFRB transcripts were identified in CD19+ cells as well as in non-CD19+ cells, suggesting the presence of a Ph+ or Ph-like ALL-M subtype originating from hematopoietic stem cells. This report provides information for better characterization, diagnosis, and treatment of these ALL subtypes.

P=N/A, N=30, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China

Case presentation: Herein, we present the case of a 23-month-old girl with high-risk B-ALL who experienced very early isolated medullary relapse; following the failure of conventional chemotherapy according to the ALL-IC REL 2016 protocol, she went on to receive the bispecific T-cell engager (BiTE) blinatumomab and subsequently, due to refractory disease, the combination of fludarabine, cytarabine, and the proteasome inhibitor bortezomib without achieving remission. The minimal residual disease (MRD) was 0.08% on day 28, and InO was continued, thus achieving MRD negativity; the patient successfully underwent an allogeneic stem cell transplantation from a matched family donor. Our case highlights the efficacy and safety of InO as a salvage treatment in the setting of relapsed B-ALL refractory not only to conventional chemotherapy but also to novel treatments, such as blinatumomab and bortezomib.

P1, N=33, Recruiting, Imugene Limited | N=52 --> 33 | Trial completion date: Sep 2025 --> May 2029 | Trial primary completion date: Sep 2024 --> Jun 2027

P1, N=10, Not yet recruiting, Amgen

P=N/A, N=36, Not yet recruiting, Shandong University

Two patients did not achieve remission even after two rounds of induction chemotherapy, with one achieving complete remission after treatment with blinatumomab immunotherapy...Five patients died, while two patients survived with sustained complete remission. TCF3-HLF-positive B-ALL is rare and has a high relapse rate and poor prognosis.

P1, N=31, Completed, Amgen | Phase classification: P1b --> P1

P1, N=28, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Jul 2025

P4, N=10, Terminated, Amgen | N=45 --> 10 | Trial completion date: Dec 2025 --> Sep 2024 | Recruiting --> Terminated | Trial primary completion date: Dec 2025 --> Sep 2024; The decision to terminate is not based on safety or efficacy but due to slow enrollment impacting the ability to complete the study as planned.

P2, N=171, Not yet recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2027 --> Dec 2028 | Initiation date: Oct 2024 --> Jan 2025 | Trial primary completion date: Dec 2027 --> Dec 2028

P3; Initiation date: Jul 2024 --> Feb 2025

P2, N=170, Active, not recruiting, St. Jude Children's Research Hospital | Recruiting --> Active, not recruiting | N=52 --> 170

CAR-MNZ bearing the CD28-OX40-CD3ζ signaling modules, and CAR-BG2, designed on the Tisagenlecleucel CAR sequence (Kymriah®), carrying the 4-1BB and CD3ζ signaling elements, were employed. CIK + Blina displayed strongest NFAT and IFN-ɣ induction, whereas CARCIK-BG2 demonstrated superior synapse formation. All the effectors have shown therapeutic activity in vivo against the CD19+ Daudi tumor model, with CARCIK cells showing a more durable response compared to CIK + Blina, likely due to the short half-life of Blina in this model.

P2/3, N=90, Recruiting, Shanghai Jiao Tong University School of Medicine

P1, N=6, Recruiting, The Children's Hospital of Zhejiang University School of Medicine

Can chemotherapy-free approaches, such as blinatumomab in conjunction with more potent TKIs, obviate the need for an allograft in high-risk patients?...Can salvage therapy and a subsequent allograft cure patients who relapse after not being transplanted in CR1? This manuscript reviews the latest data influencing contemporary management and discusses these controversies.

She was treated with modified Ph-negative EWALL induction (Vincristine, Idarubicin, dexamethasone) and achieved a complete remission. However, she subsequently experienced an early relapse and was refractory to targeted therapy with blinatumomab. After treatment with inotuzumab ozogamicin, she achieved a second complete remission...It demonstrates that patients with ostensibly favourable prognostic factors may experience poor response rates to traditional chemotherapy as well as targeted salvage agents. It also illustrates the challenges of treating B-ALL in the elderly population.

P1, N=20, Recruiting, OHSU Knight Cancer Institute | Trial completion date: Jun 2026 --> Dec 2026 | Trial primary completion date: Jun 2025 --> Dec 2025

Blinatumomab was associated with greater benefit in terms of OS and EFS relative to SC. Probabilistic, deterministic, and scenario analyses indicate that blinatumomab represents the best value for money. Therefore, blinatumomab administered as part of consolidation therapy in B-ALL pediatric patients with high-risk first relapse is a cost-effective option.

Significant progress has been made in recent years in the treatment of adults with Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL).1 Combining BCR::ABL1 tyrosine kinase inhibitors (TKIs) with intensive chemotherapy regimens like hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine (hyper-CVAD) and others has greatly improved patient outcomes.2 As a result, allogeneic hematopoietic stem cell transplantation (HSCT) has become an additional valuable option...Specifically, the 5-year PFS rates were 81% with hyper-CVAD plus ponatinib, 54% with hyper-CVAD plus dasatinib, and 64% with hyper-CVAD plus imatinib...In contrast to the D-ALBA trial, only two patients underwent HSCT.26 Whether the combination of blinatumomab and ponatinib can overcome the poor prognosis of IKZF1plus and the negative impact of an elevated white blood cell count (higher than 70×109/L, as shown in a multivariate analysis to correlate with a higher risk of relapse) remains to be determined.Asciminib is a first-in-class selective allosteric ABL myristoyl pocket (STAMP) inhibitor that was evaluated in combination with dasatinib and prednisone in a phase 1 trial of 25 patients with Ph-positive ALL, with a median age of 65 years (range, 33 to 85 years).27 Fourteen patients were enrolled in the dose-escalation cohort and 11 in the dose-expansion cohort...Eighteen patients with newly diagnosed Ph-positive ALL received dasatinib/vincristine/prednisone followed by sequential infusions of CD19 and CD22 CAR T cells...The chemotherapy-free regimens involving TKIs alongside blinatumomab have demonstrated outstanding outcomes in the frontline setting, particularly with the utilization of ponatinib. The combination of ponatinib and blinatumomab exhibits high efficacy, with CMR rates of 83% by PCR and 98% by ClonoSEQ and a 3-year OS rate of 91%, with only two patients undergoing HSCT.

P2, N=50, Not yet recruiting, Amgen

P2, N=36, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Sep 2025

He underwent cord blood transplantation with the conditioning regimen of total body irradiation plus cyclophosphamide and cytarabine with granulocyte-colony stimulating factor priming. Prophylaxis for graft versus host disease was performed with short-term methotrexate and cyclosporin...At that time, he was treated with inotuzumab ozogamicin because the blasts expressed CD22 (75.4%), but this was ineffective. He was next administered blinatumomab with dexamethasone pretreatment, resulting in a complete remission (CR)...He has still maintained a CR for 12 months. Blinatumomab might be a promising treatment and a bridge to stem cell transplantation even in relapsed/refractory CD19-expressing MPAL-B/T.

Analysis of CSF by flow cytometry showed median CD4:CD8 ratio of 1.34. In conclusion, CSF pleocytosis is prevalent with blinatumomab but only demonstrated lower rates of non-CNS extramedullary relapse but no impact on CNS relapse or neurotoxicity.

P2, N=20, Recruiting, First Affiliated Hospital of Zhejiang University

P2, N=18, Recruiting, Amgen | Not yet recruiting --> Recruiting

P2, N=52, Recruiting, St. Jude Children's Research Hospital | Trial completion date: Jul 2025 --> Jul 2026 | Trial primary completion date: Jul 2024 --> Jul 2025

P2, N=2, Active, not recruiting, University of Maryland, Baltimore | Trial primary completion date: Jun 2024 --> Jun 2025

P2, N=128, Not yet recruiting, St. Jude Children's Research Hospital

P3, N=287, Recruiting, Amgen | Trial completion date: Mar 2031 --> Oct 2031 | Trial primary completion date: May 2026 --> Jan 2027

Toll-like receptor 7 (TLR7) agonist imiquimod (IMQ) and bispecific antibody (BsAb) blinatumomab were loaded onto PDA-CaCO3 nanoparticles (NPs). PICB had a strong inhibitory effect on tumor growth in 4T1 tumor-bearing mice, and has no toxicity to other organs. Therefore, the multifunctional drug delivery nanosystem constructed in this study could effectively exert the properties of various components in vivo, fully demonstrate the synergistic effect between immunotherapy and photothermal therapy, thus significantly improving the tumor therapeutic efficacy, and has a promising clinical application.

The addition of blinatumomab to consolidation chemotherapy in adult patients in MRD-negative remission from BCP-ALL significantly improved overall survival. (Funded by the National Institutes of Health and others; E1910 ClinicalTrials.gov number, NCT02003222.).

P1, N=4, Recruiting, The First Affiliated Hospital of Soochow University

P=N/A, N=20, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China

P1/2, N=40, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting

After two cycles of blinatumomab, he underwent allogeneic bone marrow transplantation (BMT) from his human leukocyte antigen (HLA)-matched sibling, following conditioning with total body irradiation, etoposide, and cyclophosphamide. A t-distributed symmetric neighbor embedding (tSNE) analysis revealed that blinatumomab altered the CD8+ population, as with pre-HSCT use, and markedly reduced the CD8+19dim+/CD8+CD19- ratio (i.e., naïve lymphocyte predominance). Blinatumomab maintenance therapy after HSCT may be considered a safe treatment.

Of these, there is promising early data on the efficacy and tolerability of the bi-specific T-cell engager monoclonal antibody, blinatumomab, as well as the use of autologous and allogeneic chimeric antigen receptor T-cell therapy. We discuss how we can improve risk stratification and incorporate these new agents to replace the most toxic elements of currently deployed intensive chemotherapy schedules with their associated unacceptable toxicity.

P3, N=287, Recruiting, Amgen | Trial completion date: Sep 2031 --> Feb 2031 | Trial primary completion date: Dec 2026 --> May 2026