Daratumumab

Recent data highlights the use of novel therapies, including monoclonal antibodies and T-cell engagers, which offer high efficacy with different toxicity profiles.

Daratumumab, which is an anti-CD38 monoclonal antibody, has shown significant utility.

Daratumumab binds directly to the CD38 protein highly expressed on the surface of the clonal plasma cells, inducing rapid cell death through complement-dependent cytotoxicity.

In relapsed or refractory patients, daratumumab-based regimens achieved a hematologic complete response in about 30% of patients, providing a critical salvage option.

Right.

What made it up?

J&J credits Tremfya, its newer immunology antibody, along with cancer drugs including Darzalex and Carvykti.

On J&J's figures, excluding currency, oncology grew about seventeen percent and Tremfya about sixty-eight percent.

MedTech, the devices side, grew just two point five percent on the same basis, short of J&J's own expectations.

Today, we are speaking with Dr. Sagar Lonial, professor and chair of the Department of Hematology and Medical Oncology at Emory University School of Medicine, chief medical officer at Winship Cancer Institute, and lead investigator of the Phase 3 ExCALIBUR Trial, new findings from which he presented at the recent IMS 2026 annual meeting.

In this episode, Lonial breaks down these data, how the study arm of iberdomide, daratumumab, dexamethasone demonstrated an MRD negativity rate of 41% compared with 20% seen for the comparator arm of daratumumab, bortezomib, dexamethasone.

How dosing was chosen for fit rather than force by testing iberdomide doses of 1, 1.3 and 1.6 milligrams, and why MRD as an endpoint has potential to get new therapeutics to patients faster.

He also explains how he manages neutropenia with dose holds and GCSF versus early dose reductions and where mezigdomide fits in.

I think what we were able to do with stage 1 of EXCALIBUR was really identify what is the optimal dose, and this again is unique.

Mo- all the IMiDs are dosed to MTD, maximum tolerated dose.

In EXCALIBUR, both the relapsed and the maintenance trial, this two-stage design was employed to understand, in that given clinical context, what is the optimal dose? An optimal dose takes not only efficacy, but also safety into account, and what we found was that the 1 milligram dose was a better partner with daratumumab.

And as you may recall, when we combined dara with either len or pom, the neutropenia does go up.

This is the Majestic 3, which was a late-breaking abstract last year and now published in the New England Journal of Medicine.

And what is the rationale of combining it with an anti-CD38 monoclonal antibody? The reason to do this is you have direct anti-myeloma activity with daratumumab.

Daratumumab, as you all know, or any anti-CD38 monoclonal antibody, depletes immunosuppressive T cells, and it also enhances CD8 T cell cytotoxicity.

So the combinations seem to be a rational approach in this case.

So this is the data with the MAJESTIC-3 trial, teclistamab and daratumumab versus standard of care.

He couldn't give me any certainty about anything.

And so my initial treatment went through cycles Which I went through six cycles, and that included medications such as Darzalex, Velcade, Decatron, and Revlimid.

Mm.

After that I was treated with Revlimid, Decatron [laughs] and the other one Kyprolis.

El frente frío número uno provocará lluvias intensas hasta el 8 de octubre en estados del oriente y sureste del país, como Tamaulipas, Veracruz, Puebla, Oaxaca y Yucatán.

Cofepris alertó sobre la adulteración de dos lotes del medicamento Aderogyl y advirtió por la falsificación de los fármacos Darzalex y Simponi.

Le fue dictada prisión preventiva a Miguel N., alias Capitán Sol, por delincuencia organizada y delitos relacionados con huachicol.

La audiencia será el jueves.

First-line treatment, bortezomib, lenalidomide, dexamethasone.

Daratumumab, anti, CD38 monoclonal antibody now in first-line regimens.

Supportive, bisphosphonates, hydration, infection prophylaxis.

Hyperviscosity, visual disturbance, headache, bleeding.