Blincyto (blinatumomab)

P2, N=53, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2026 --> Jan 2027

P2, N=69, Active, not recruiting, St. Jude Children's Research Hospital | N=140 --> 69 | Trial completion date: Aug 2025 --> Jun 2026

P1/2, N=104, Recruiting, University of Chicago | Not yet recruiting --> Recruiting

P3, N=560, Not yet recruiting, Amgen | Trial completion date: Mar 2033 --> Aug 2033 | Initiation date: Jan 2026 --> Jun 2026 | Trial primary completion date: Dec 2029 --> May 2030

P=N/A, N=330, Not yet recruiting, PETHEMA Foundation

Currently, most leukemias are effectively treated with immunotherapies (highly effective monoclonal antibodies targeting CD19 [blinatumomab], or CD22 [inotuzumab ozogamicin]), BCR::ABL1 tyrosine kinase inhibitors (TKIs; e.g., dasatinib, ponatinib), Bruton TKIs (e.g., ibrutinib, acalabrutinib), BCL-2 inhibitors (venetoclax), IDH1/2 inhibitors (ivosidenib, olutasidenib, and enasidenib), FLT3 inhibitors (e.g., midostaurin, quizartinib, and gilteritinib), menin inhibitors (revumenib, ziftomenib), and chimeric antigen receptor T-cell therapies. Herein, we provide a high-level overview of prominent clinical developments across all leukemias. In contemporary times, harnessing the benefits of novel targeted therapies and the evolving treatment landscape bolster the optimistic view that most, if not all, leukemias are curable.

Following induction therapy, sequential therapy with blinatumomab and ponatinib achieved qualitatively PCR-negative minor BCR::ABL1 transcripts, indicating that residual transcripts below the qualitative assay's detection limit were undetectable. She received an allogeneic bone marrow transplant and remains well with PCR-negative minor BCR::ABL1 at 15 months after transplantation. This sequential therapy suggests a potential utility as a bridge to hematopoietic stem cell transplantation for secondary CML-BP with CD19+ mixed phenotype.

P2, N=220, Recruiting, Amgen | N=98 --> 220 | Trial completion date: Jun 2029 --> Mar 2029 | Trial primary completion date: Sep 2028 --> Jan 2028

In conclusion, encouraging activity was seen with blinatumomab and lenalidomide in heavily pretreated R/R B-NHL (NCI Protocol no. 9924).

Despite recent advancements, patients with B-cell ALL tend to have poorer outcomes, especially in the adult population. Future research and larger scale prospective studies are indicated to evaluate the efficacy of InO in different lines of therapy.

Notably, zoledronate-expanded Vγ9Vδ2 γδ T-cell lines achieved cytotoxicity comparable to PHA-expanded αβ cells. Together, these in vitro data reveal subset-specific BLN responses and support the hypothesis that ex vivo-expanded Vγ9Vδ2 γδ T cells could complement BLN-mediated cytotoxicity, particularly under conditions of higher CD19 density and lower target burden. These findings provide a mechanistic framework for future testing of γδ T-cell/BLN combination strategies in patient-derived models and clinical studies.

P=N/A, N=300, Recruiting, Arkansas Children's Hospital Research Institute