Darzalex (daratumumab)

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

P2, N=160, Recruiting, Institute of Hematology & Blood Diseases Hospital, China

The patient achieved short-term remission with bortezomib in combination with etoposide, dexamethasone, cyclophosphamide, and doxorubicin as first-line therapy. After disease progression, the patient received daratumumab combined with GemOx as second-line treatment but showed no response...The patient received CD19 and CD22 CAR-T therapies as the third-line treatment and achieved durable complete remission for more than one year with good tolerance. A patient with refractory PBL achieved durable complete remission after CD19 and CD22 CAR-T therapies, suggesting this treatment may be effective for patients with refractory or relapsing PBL.

Stratifying patients with MM based on myeloma cell maturity provides meaningful information for choosing the best treatment strategy and improving patient outcomes.

P2, N=50, Not yet recruiting, University of Arkansas | Initiation date: Oct 2025 --> Apr 2026

At the patient's request, six cycles of systemic chemotherapy with daratumumab, lenalidomide, and dexamethasone (DRd) were administered, leading to further shrinkage without complete response. This rare case of solitary plasmacytoma showed residual disease post definitive radiotherapy. In those residual tumors, close long-term monitoring is crucial.

P2, N=160, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College; Institute of Hematology