^
8d
Long-Term Benefits in Patient-Reported Outcomes and Time to Next Anti-Myeloma Therapy of Ciltacabtagene Autoleucel (Cilta-cel) Versus Standard of Care for Patients with Lenalidomide-Refractory Multiple Myeloma: Results from the Phase 3 Cartitude-4 Clinical Trial (ASH 2024)
"Background: Ciltacabtagene autoleucel (cilta-cel) demonstrated superior progression-free survival (PFS) and overall survival compared to standard of care (SOC; pomalidomide, bortezomib, and dexamethasone or daratumumab, pomalidomide, and dexamethasone) in patients with lenalidomide-refractory multiple myeloma (MM) after 1-3 prior lines of therapy (LOTs) in the phase 3 CARTITUDE-4 trial. The increase in the TTNT and sustained benefits in PROs, along with prolonged survival, support cilta-cel as a new SOC treatment for MM patients who are refractory to lenalidomide and have received 1-3 prior LOTs. Importantly, with ~3 years of follow-up, a single infusion of cilta-cel provided patients with a longer delay in worsening of MM related symptoms, functional impacts, and GHS/QoL. The totality of clinical and patient-reported evidence demonstrates the significant benefit of cilta-cel."
P3 data • Clinical • Patient reported outcomes
|
lenalidomide • bortezomib • Darzalex (daratumumab) • dexamethasone • pomalidomide • Carvykti (ciltacabtagene autoleucel)
8d
Pharmacodynamic Signatures and Correlatives of Response in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) Treated with Talquetamab or Teclistamab Plus Daratumumab and Pomalidomide (ASH 2024)
P1 | "Tal-DP exhibits a deep, long-term impact on efficacy through complementary mechanisms of action and may be especially beneficial in pts with prior BsAb exposure, who typically have unfavorable BL immune profiles. Ongoing analyses of tec-DP from MajesTEC-2 (NCT04722146) will be presented."
PK/PD data • Clinical
|
Darzalex (daratumumab) • pomalidomide • Talvey (talquetamab-tgvs) • Tecvayli (teclistamab-cqyv)
16d
Rapid DFLC Response Predict CHR in AL Amyloidosis (clinicaltrials.gov)
P=N/A, N=50, Recruiting, Peking University People's Hospital | Not yet recruiting --> Recruiting
Enrollment open
|
bortezomib • cyclophosphamide • Darzalex (daratumumab) • Darzalex Faspro (daratumumab and hyaluronidase-fihj)
16d
Trial completion date
|
TP53 (Tumor protein P53)
|
TP53 mutation
|
Imbruvica (ibrutinib) • Darzalex (daratumumab)
22d
Daratumumab in Treating Patients with Muscle Invasive Bladder Cancer or Metastatic Kidney Cancer (clinicaltrials.gov)
P1, N=17, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jun 2024 --> Jun 2026 | Trial primary completion date: Jun 2024 --> Jun 2026
Trial completion date • Trial primary completion date
|
PD-L1 (Programmed death ligand 1)
|
Darzalex (daratumumab)
23d
A Study to Assess the Adverse Events and Change in Disease Activity in Adult Participants With Relapsed or Refractory Multiple Myeloma Receiving Oral ABBV-453 Tablets (clinicaltrials.gov)
P1, N=34, Active, not recruiting, AbbVie | Recruiting --> Active, not recruiting | N=360 --> 34 | Trial completion date: Aug 2026 --> Dec 2025 | Trial primary completion date: Aug 2026 --> Feb 2024
Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date • Adverse events • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2)
|
Chr t(11;14)
|
lenalidomide • Darzalex (daratumumab) • dexamethasone • ABBV-453
27d
miR‑1343‑3p inhibits autophagy by directly targeting ATG7 in multiple myeloma cells. (PubMed, Biomed Rep)
Despite application of several new drugs, such as daratumumab, bortezomib/lenalidomide/dexamethasone, in combination with hematopoietic stem cell transplantation, overall prognosis remains poor and the pathological mechanism of MM is still unknown. The present findings suggested that miR-1343-3p may regulate ATG7 and autophagy by directly targeting the 3'UTR of ATG7. To the best of our knowledge, there are no direct data showing the roles of miR-1343-3p in development of MM; however, miR-1343-3p may be considered a potential target for MM treatment.
Journal
|
ATG7 (Autophagy Related 7) • MIR134 (MicroRNA 134)
|
lenalidomide • bortezomib • Darzalex (daratumumab) • dexamethasone
28d
CAMMA 1: A Study Evaluating the Safety, Pharmacokinetics, and Activity of Cevostamab in Participants With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov)
P1, N=184, Recruiting, Genentech, Inc. | Trial completion date: Jul 2025 --> Jan 2026 | Trial primary completion date: Sep 2024 --> Jan 2026
Trial completion date • Trial primary completion date
|
Darzalex (daratumumab) • dexamethasone • pomalidomide • Actemra IV (tocilizumab) • cevostamab (RG6160)
29d
Characterising how a single bout of exercise in people with myeloma affects clonal plasma cell and immune effector cell frequency in blood, and daratumumab efficacy in vitro. (PubMed, Brain Behav Immun Health)
However, plasma cells were largely unchanged, and NK-cells expressing CD38 - the daratumumab target antigen - increased in blood. Future research should consider the optimal timings of exercise during daratumumab treatment in myeloma to avert exacerbation of daratumumab-mediated NK-cell lysis.
Preclinical • Journal
|
PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • NCAM1 (Neural cell adhesion molecule 1) • SDC1 (Syndecan 1) • CD14 (CD14 Molecule) • FCGR2A (Fc fragment of IgG receptor IIa) • FCGR2B (Fc Fragment Of IgG Receptor IIb)
|
CD38 expression
|
Darzalex (daratumumab)
30d
Dara-RVd Induction for Newly Diagnosed Multiple Myeloma With Autologous Stem Cell Transplantation (clinicaltrials.gov)
P2, N=39, Not yet recruiting, UNC Lineberger Comprehensive Cancer Center | Initiation date: Sep 2024 --> Dec 2024
Trial initiation date
|
lenalidomide • bortezomib • Darzalex (daratumumab) • dexamethasone
1m
MonumenTAL-8: A Study of Ciltacabtagene Autoleucel and Talquetamab for the Treatment of Participants With High-Risk Multiple Myeloma (clinicaltrials.gov)
P2, N=30, Recruiting, Janssen Research & Development, LLC | Trial completion date: Apr 2028 --> Feb 2027
Trial completion date
|
lenalidomide • Darzalex (daratumumab) • dexamethasone • Carvykti (ciltacabtagene autoleucel) • Talvey (talquetamab-tgvs)
1m
Trial completion date • Trial primary completion date
|
clonoSEQ
|
lenalidomide • bortezomib • Darzalex (daratumumab) • dexamethasone
1m
2015-12: a Study Exploring the Use of Early and Late Consolidation/Maintenance Therapy (clinicaltrials.gov)
P2, N=50, Active, not recruiting, University of Arkansas | Trial completion date: Oct 2025 --> Oct 2026 | Trial primary completion date: Oct 2024 --> Oct 2025
Trial completion date • Trial primary completion date
|
cisplatin • lenalidomide • bortezomib • doxorubicin hydrochloride • cyclophosphamide • etoposide IV • Darzalex (daratumumab) • carfilzomib • thalidomide • melphalan
1m
Trial completion • Combination therapy
|
bortezomib • Darzalex (daratumumab) • prednisone • melphalan • Darzalex Faspro (daratumumab and hyaluronidase-fihj) • dexamethasone injection
1m
Targeting CD38 with monoclonal antibodies disrupts key survival pathways in paediatric Burkitt's lymphoma malignant B cells. (PubMed, Clin Transl Immunology)
This study investigates the effectiveness of CD38-targeting monoclonal antibodies (mAbs), daratumumab and isatuximab, in impairing crucial cellular processes and survival pathways in pBL malignant cells. The study also revealed a correlation between CD38 and MYC expression levels in pBL patient samples, suggesting CD38 involvement in key oncogenic processes. The study emphasises the therapeutic potential of CD38-targeting mAbs, particularly isatuximab, in pBL.
Journal • IO biomarker
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog)
|
MYC expression
|
Darzalex (daratumumab) • Sarclisa (isatuximab-irfc)
1m
Rapid dFLC Response Predict CHR in AL Amyloidosis (clinicaltrials.gov)
P=N/A, N=50, Not yet recruiting, Peking University People's Hospital
New trial
|
bortezomib • cyclophosphamide • Darzalex (daratumumab) • Darzalex Faspro (daratumumab and hyaluronidase-fihj)
1m
First use of 18F-FDG PET in TEMPI syndrome: can it be used for treatment assessment? A case report. (PubMed, Front Nucl Med)
Post-treatment 18F-FDG PET (Daratumumab Bortezomib Thalidomide Dexamethasone) revealed a completely reduced signal of bone lesions, suggesting a complete response, which was substantiated both clinically and biologically, with the concurrent disappearance of telangiectasia and the monoclonal component, and the normalization of the EPO level. In future, additional data will be required to confirm the added value of 18F-FDG PET with TEMPI. Nevertheless, 18F-FDG PET can be a preferred tool for the extension workup and therapeutic evaluation of TEMPI syndrome.
Journal • IO biomarker • FDG PET
|
JAK2 (Janus kinase 2) • CD38 (CD38 Molecule) • SDC1 (Syndecan 1)
|
JAK2 mutation
|
bortezomib • Darzalex (daratumumab) • dexamethasone • thalidomide
1m
Daratumumab-bortezomib-dexamethasone (Dara-VCd) vs Bortezomib-Thalidomide-Dexamethasone (VTd), Then Maintenance With Ixazomib (IXA) or IXA-Dara (clinicaltrials.gov)
P2, N=401, Active, not recruiting, Stichting European Myeloma Network | Trial completion date: Feb 2025 --> Feb 2026 | Trial primary completion date: May 2024 --> Jun 2025
Trial completion date • Trial primary completion date
|
IGH (Immunoglobulin Heavy Locus)
|
bortezomib • cyclophosphamide • Ninlaro (ixazomib) • Darzalex (daratumumab) • thalidomide • melphalan
2ms
Phase 1b/2 trial of iberdomide in combination with daratumumab, dexamethasone +/- carfilzomib to eliminate MRD after induction therapy and ASCT in NDMM (IMW 2024)
Iber-Dd and Iber-DKd are safe combinations and able to eliminate MRD persistent after modern induction therapy and ASCT in NDMM. This study is ongoing, complete safety and efficacy results from part 1 and updated results from part 2 will be presented at the meeting.
Combination therapy • P1/2 data
|
CRBN (Cereblon)
|
clonoSEQ
|
Darzalex (daratumumab) • carfilzomib • dexamethasone • iberdomide (CC-220)
2ms
New P3 trial • CAR T-Cell Therapy
|
lenalidomide • cyclophosphamide • Darzalex (daratumumab) • carfilzomib • dexamethasone • pomalidomide • fludarabine IV • BMS-986393
2ms
Selinexor, Daratumumab, Carfilzomib and Dexamethasone for the Treatment of High-Risk, Recurrent or Refractory Multiple Myeloma (clinicaltrials.gov)
P2, N=52, Active, not recruiting, Academic and Community Cancer Research United | Recruiting --> Active, not recruiting
Enrollment closed
|
Chr t(4;14) • Chr t(14;16) • Chr del(1p)
|
Xpovio (selinexor) • Darzalex (daratumumab) • carfilzomib
2ms
A Novel Tetravalent Bispecific Immune Cell Engager Activates Natural Killer Cells to Kill Cancer Cells without Mediating Fratricide. (PubMed, Antibodies (Basel))
Notably, our findings showed that daratumumab-induced NK fratricide was restricted to CD38-CD38 crosslinking and was not related to ADCC via CD16a-CD38 crosslinking. This study is the first in the literature to show the successful engineering of a tetravalent immune cell engager composed of tandem VHH units, which achieves high affinity and anticancer activity without mediating fratricide.
Journal • Immune cell
|
FCGR3A (Fc Fragment Of IgG Receptor IIIa)
|
Darzalex (daratumumab)
2ms
Enrollment open
|
lenalidomide • Darzalex (daratumumab) • dexamethasone • Carvykti (ciltacabtagene autoleucel) • Talvey (talquetamab-tgvs)
2ms
STOMP: Selinexor and Backbone Treatments of Multiple Myeloma Patients (clinicaltrials.gov)
P1/2, N=300, Recruiting, Karyopharm Therapeutics Inc | Active, not recruiting --> Recruiting
Enrollment open • Combination therapy
|
lenalidomide • bortezomib • Xpovio (selinexor) • Ninlaro (ixazomib) • Darzalex (daratumumab) • carfilzomib • pomalidomide • Empliciti (elotuzumab) • Blenrep (belantamab mafodotin-blmf) • mezigdomide (CC-92480)
2ms
Trial completion date
|
lenalidomide • bortezomib • Darzalex (daratumumab) • dexamethasone
2ms
AMC-105: A Study of Daratumumab and Dose-Adjusted EPOCH in Plasmablastic Lymphoma (clinicaltrials.gov)
P1, N=15, Active, not recruiting, AIDS Malignancy Consortium | Recruiting --> Active, not recruiting
Enrollment closed
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CD4 (CD4 Molecule)
|
MYC expression
|
doxorubicin hydrochloride • cyclophosphamide • etoposide IV • Darzalex (daratumumab) • vincristine • daunorubicin
2ms
Daratumumab and Ibrutinib for the Treatment of Relapsed or Refractory Chronic Lymphocytic Leukemia, DIRECT Study (clinicaltrials.gov)
P2, N=11, Active, not recruiting, Mayo Clinic | Trial completion date: Feb 2026 --> Oct 2027
Trial completion date
|
Imbruvica (ibrutinib) • Darzalex (daratumumab)
2ms
Interferon Regulatory Factor 4: An Alternative Marker for Plasma Cells in Daratumumab-Treated Patients With Multiple Myeloma. (PubMed, Int J Lab Hematol)
IRF-4 demonstrates high MFI on PCs, and it is not expressed on other leukocytes. In MM patients with MRD, daratumumab treatment does not affect IRF-4 expression. IRF-4 is a promising marker for PC identification in MRD assessment of MM patients undergoing anti-CD38 therapy.
Journal • IO biomarker
|
TNFRSF17 (TNF Receptor Superfamily Member 17) • LY9 (Lymphocyte Antigen 9) • SDC1 (Syndecan 1) • IRF4 (Interferon regulatory factor 4)
|
IRF4 expression
|
Darzalex (daratumumab)
2ms
Phase II clinical trial of minimal residual disease response-adapted deferral of transplantation in dysproteinemia (MILESTONE) (IMW 2024)
In cohort A (NDMM), treatment consists of daratumumab 1800 mg SC (typical schedule), weekly bortezomib 1.3 mg/m2 SC, lenalidomide 25 mg PO days 1-21 and weekly dexamethasone 40 mg PO/IV (DaraVRd) every 28 days for 6 cycles followed by assessment of MRD by next-generation sequencing (clonoSEQ). Quadruplet induction results in deep responses allowing an opportunity to defer ASCT based on individual treatment response in NDMM. This study provides the initial feasibility of utilization of post induction MRD in guiding next steps in treatment. This approach is being further explored in the larger ongoing, randomized phase II MASTER-2 clinical trial to see if comparable clinical outcomes are possible without ASCT in those achieving deep response to induction therapy.
P2 data • Clinical • Minimal residual disease
|
CD34 (CD34 molecule)
|
clonoSEQ
|
lenalidomide • bortezomib • Darzalex (daratumumab)
2ms
Liquid chromatography mass spectrometry (LC-MS) for identification of exceptional responders in newly diagnosed multiple myeloma (NDMM). (IMW 2024)
Patients were treated either with carfilzomib, lenalidomide, and dexamethasone plus autologous stem cell transplant (KRd-ASCT, NCT01816971) or with daratumumab, carfilzomib, lenalidomide, and dexamethasone (Dara-KRd, NCT03500445). In addition to the prognostic significance of MS(-) at any level, the depth of MS negativity is associated with longer PFS. LC-MS(-) and/or 10-6 MRD(-) patients experience long term disease control. The potential of LC-MS to enhance the prognostic potential of MRD at 10-6 for predicting longer disease control is currently under evaluation in a larger sample set.
clonoSEQ
|
lenalidomide • Darzalex (daratumumab) • carfilzomib • dexamethasone
2ms
Isatuximab for Delayed Red Cell Engraftment after Allogeneic Hematopoietic Cell Transplantation. (PubMed, Case Rep Hematol)
She received therapy with rituximab, bortezomib, prednisone, and darbepoetin alfa with partial to no response. After repeated insurance denials for daratumumab, isatuximab was obtained from the manufacturer through their CareASSIST program. Following the completion of 2 cycles of isatuximab (8 doses), significant and sustained red cell recovery was observed.
Journal
|
HLA-B (Major Histocompatibility Complex, Class I, B)
|
Rituxan (rituximab) • bortezomib • Darzalex (daratumumab) • prednisone • Sarclisa (isatuximab-irfc) • Aranesp (darbepoetin alfa)
3ms
CheckMate 039: An Investigational Immuno-Therapy Study to Determine the Safety and Effectiveness of Nivolumab and Daratumumab in Patients With Multiple Myeloma (clinicaltrials.gov)
P1/2, N=316, Completed, Bristol-Myers Squibb | Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Jul 2024
Trial completion • Trial completion date
|
Opdivo (nivolumab) • Yervoy (ipilimumab) • Darzalex (daratumumab) • dexamethasone • pomalidomide • lirilumab (BMS-986015)
3ms
T-ALL-2024: Daratumumab for T Cell ALL With MRD-positive After Standard Chemotherapy (clinicaltrials.gov)
P2, N=20, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China
New P2 trial • Minimal residual disease
|
Darzalex (daratumumab)
3ms
AL38: AL Amyloidosis and Anti-CD38-Daratunumab (clinicaltrials.gov)
P=N/A, N=14, Completed, University of Turin, Italy
New trial
|
Darzalex (daratumumab)
3ms
FCGR3A F158V alleles frequency differs in multiple myeloma patients from healthy population. (PubMed, Oncoimmunology)
However, we did not observe difference in response following treatment combining chemotherapy associated or not with daratumumab, an IgG1 mAb direct against CD38. Our findings suggest that FCGR3A F158V polymorphism can regulate the immune environment and affect the development of tumor plasma cells.
Journal • IO biomarker
|
CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • FCGR3A (Fc Fragment Of IgG Receptor IIIa)
|
Darzalex (daratumumab)
3ms
Enrollment change
|
Imbruvica (ibrutinib) • Darzalex (daratumumab)
3ms
Enrollment open
|
bortezomib • cyclophosphamide • Darzalex (daratumumab) • carfilzomib • dexamethasone • pomalidomide • fludarabine IV • anitocabtagene autoleucel (CART-ddBCMA)
3ms
IPoD-790: Ixazomib-pomalidomide-dexamethasone as Second or Third-line Combination Treatment for Patients With Relapsed and Refractory Multiple Myeloma Previously Treated With Daratumumab, Lenalidomide and Bortezomib (clinicaltrials.gov)
P2, N=60, Active, not recruiting, Tel-Aviv Sourasky Medical Center | Trial completion date: Oct 2024 --> Sep 2029 | Trial primary completion date: Sep 2024 --> Mar 2026
Trial completion date • Trial primary completion date
|
lenalidomide • bortezomib • Ninlaro (ixazomib) • Darzalex (daratumumab) • dexamethasone • pomalidomide
3ms
FeAsiBility of a Treatment Free Interval in Newly Diagnosed MM Patients Treated With Daratumumab-lenalidomide-dexamethasone (HOVON174MM) (clinicaltrials.gov)
P3, N=599, Recruiting, Stichting Hemato-Oncologie voor Volwassenen Nederland | Not yet recruiting --> Recruiting
Enrollment open
|
lenalidomide • Darzalex (daratumumab) • dexamethasone injection
3ms
CENTAURUS: A Study to Evaluate 3 Dose Schedules of Daratumumab in Participants With Smoldering Multiple Myeloma (clinicaltrials.gov)
P2, N=123, Completed, Janssen Research & Development, LLC | Active, not recruiting --> Completed
Trial completion
|
Darzalex (daratumumab)
3ms
Enrollment closed
|
lenalidomide • bortezomib • Ninlaro (ixazomib) • Darzalex (daratumumab) • dexamethasone • pomalidomide