Darzalex (daratumumab)

Bispecific antibodies such as blinatumomab (anti-CD19), antibody-drug conjugates like inotuzumab ozogamicin (anti-CD22), and monoclonal antibodies such as daratumumab (anti-CD38) have demonstrated efficacy in relapsed or refractory disease with improved safety profiles. The integration of targeted and immune-based therapies into conventional regimens represents a decisive step toward precision medicine, aiming to enhance survival outcomes while reducing treatment-related toxicity and improving quality of life in ALL children. This review aims to provide a comprehensive overview of the current understanding of ALL pathobiology and therapeutic approaches, with particular emphasis on the expanding role of immunotherapeutic strategies in pediatric disease.

P2, N=5, Terminated, University Hospital, Grenoble | Phase classification: P=N/A --> P2 | N=12 --> 5 | Recruiting --> Terminated; limited clinically significant reduction on global cPRA levels (access to transplantation was unchanged), as well as restrictions in belatacept supply.

P3, N=1000, Recruiting, European Myeloma Network B.V. | Not yet recruiting --> Recruiting

P2, N=31, Active, not recruiting, City of Hope Medical Center | Trial completion date: Nov 2025 --> Jul 2026 | Trial primary completion date: Nov 2025 --> Jul 2026

Recent advancements in treatment involve using novel agents like bortezomib, daratumumab, and B-cell maturation antigen-targeted therapy, which are improving outcomes; however, the prognosis for relapsed disease remains poor. The best remission chances come from rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy combined with central nervous system-directed treatment. New research is ongoing for relapsed cases.

Rituximab is now the preferred second-line option for relapsed/refractory patients, comparing favorably with the traditional splenectomy. The latter is increasingly reserved for later lines together with classic immunosuppressants. Several novel treatments are in development for refractory wAIHA, encompassing drugs targeting B-cells (parsaclisib, ibrutinib, rilzabrutinib, zanubrutinib, obexelimab, ianalumab, povetacicept), plasma cells (bortezomib, daratumumab), spleen tyrosine kinase (fostamatinib, sovleplenib), and the neonatal Fc receptor (nipocalimab).

Our study examined two "first-in-class" RNA Pol I inhibitors, CX-5461 and BMH-21, which differentially regulate NK cell-activating and inhibitory ligand expression in MM. This effect was modulated by Lenalidomide and Panobinostat. Moreover, RNA Pol I inhibition enhanced Daratumumab-mediated antibody-dependent cellular cytotoxicity (ADCC) of NK cells against MM, uncovering novel immuno-mediated antitumor mechanisms.

Treatment regimens comprised lenalidomide (n = 36) or thalidomide (n = 15) with daratumumab, and pomalidomide (n = 2) with isatuximab. Most patients (n = 38) received frontline therapy, and all were given thromboprophylaxis according to guidelines, mainly aspirin (73%)...Given the limited number of patients and thrombotic events, and the cytokine data available for only two VTE cases, these associations should be regarded as exploratory and interpreted with caution. Overall, these exploratory findings warrant validation in larger, independent cohorts and may help generate hypotheses on how inflammatory signatures influence thrombotic risk and prophylaxis efficacy in MM patients receiving IMiD/anti-CD38-based regimens.

P=N/A, N=359, Completed, iOMEDICO AG | Active, not recruiting --> Completed

Background/Objectives: The role of daratumumab, lenalidomide, and dexamethasone (DRd) in autologous stem cell transplantation (ASCT)-eligible patients with multiple myeloma (MM) after first-line bortezomib, cyclophosphamide, and dexamethasone (VCd) treatment is not yet established. However, hypogammaglobulinemia was more common in the salvage group (75% vs. 15%, p = 0.018). This small case series suggests that DRd is promising for ASCT-eligible patients with MM after VCd failure.

P2, N=75, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial primary completion date: Sep 2026 --> May 2025

P=N/A, N=450, Recruiting, Brigham and Women's Hospital | Trial primary completion date: Jun 2025 --> Jun 2026