Darzalex (daratumumab)

Daratumumab-mediated disruption of mitochondrial transfer reduced the mitochondrial content in MM cells, prevented the boost in OXPHOS, significantly impaired MM cell growth and migration, and mitigated drug-resistance. In conclusion, we reveal a crucial metabolic interplay between monocytes and MM cells within the BM microenvironment that promotes tumor growth and induces therapy resistance, providing the rationale for treatment strategies that combine targeting tumor metabolism with existing anti-MM agents.

We report a 69-year-old man with resectable stage IIB right upper lobe lung adenocarcinoma who received neoadjuvant pembrolizumab, carboplatin, and pemetrexed followed by robotic-assisted lobectomy. He received adjuvant pembrolizumab and daratumumab-CyBorD with partial hematologic response. This case highlighted that amyloid can unexpectedly be a second diagnosis after post-neoadjuvant lung resections and that proteomic subtyping is essential for prompt haematologic staging and treatment.

In our real-life study, we confirmed the strong negative impact of lenalidomide on PBSC collection by comparing lenalidomide-treated patients with a control cohort of thalidomide-treated subject, also showing a more frequent use of plerixafor to mitigate these effects, thereby reducing the reliance on cyclophosphamide, that was associated with lower risk of prolonged apheresis sessions. Indeed, we showed that lenalidomide use significantly impaired stem cell collection, with prolonged apheresis sessions and lower CD34+ cell collection on day 1, while post-transplant outcomes did not significantly differ between groups. Our real-life bi-center experience is of great interest in the era of daratumumab-based regimens as first-line therapy for autologous stem cell transplantation-eligible MM patients, because the concomitant use with lenalidomide might negatively affect PBSC mobilization, urging for more tailored PBSC collection strategies.

P=N/A, N=300, Not yet recruiting, The Royal Wolverhampton Hospitals NHS Trust

P2, N=150, Recruiting, European Myeloma Network B.V. | Not yet recruiting --> Recruiting

P1, N=12, Not yet recruiting, Medical College of Wisconsin | Initiation date: Mar 2026 --> Jul 2026

P=N/A, N=40, Recruiting, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico | Active, not recruiting --> Recruiting

CD38 overexpression in GBM drives tumor progression by amplifying immunosuppressive TME remodeling, positioning CD38 as a compelling target for further clinical investigation, supported by preliminary efficacy of daratumumab (NCT04922723) in patients with GBM.

P=N/A, N=40, Active, not recruiting, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

P1/2, N=246, Recruiting, BeOne Medicines | Active, not recruiting --> Recruiting

Although Dara-VTd induction is associated with impaired mobilization kinetics, successful steady-state mobilization remains feasible. On-demand plerixafor use overcomes mobilization deficits, supporting this approach in patients receiving CD38-based quadruplet induction therapy. Furthermore, follow-up analysis of stem cell graft utilization demonstrates a high proportion of collected but unused stem cell grafts in both cohorts.

P1/2, N=246, Active, not recruiting, BeOne Medicines | Recruiting --> Active, not recruiting