Darzalex (daratumumab) / Genmab, J&J - LARVOL DELTA

Johnson & Johnson today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has granted approval for a Type II variation to the labelling for DARZALEX (daratumumab) subcutaneous (SC) formulation. (The Manila Times) - "The label update enables patients living with multiple myeloma or their caregivers to administer daratumumab from the fifth dose, if determined to be appropriate by their healthcare professional and following proper training....It applies to all ten therapeutic indications of daratumumab SC for multiple myeloma, smouldering multiple myeloma and light chain (AL) amyloidosis."

CHMP • Amyloidosis • Multiple Myeloma

Oncolytic bovine herpesvirus type 1 induces immune microenvironment remodeling and enhances treatment responses in multiple myeloma. (PubMed, Haematologica) - "Co-treatment of BoHV-1 with either bortezomib or lenalidomide increased anti-MM cytotoxicity. Finally, BoHV-1 upregulated CD38 on both MM cells and immune effectors, thereby increasing sensitivity to the anti-CD38 daratumumab. These findings establish BoHV-1 as a promising immunovirotherapy agent, effective as a single agent and in combination strategies, by coupling direct oncolysis with broad immune remodeling of the BM microenvironment."

Journal • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Oncology • CD8

Vitamin D receptor expression in germinal centre type diffuse large B-cell lymphoma cells is associated with vitamin D insensitivity. (PubMed, Endocr Oncol) - "CD38 is also activated by VitD3 treatment of human peripheral B cell lines, where VDR can bind to the CD38 locus, suggesting direct regulation. Combined VDR and cell-of-origin assessment may contribute to a greater understanding of vitamin D's role in mature B-cell lymphoma and its interplay with BCL6 and MYC."

IO biomarker • Journal • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • BCL6 • CD38 • MYC • VDR

Treatment with Daratumumab in Combination with Glucocorticosteroids as First-Line Treatment Achieves a Complete Remission for a Patient with Multiple Myeloma and Resolves Neutropenia: A Case Report. (PubMed, Case Rep Oncol) - "This case highlights the potential for daratumumab combined with glucocorticosteroids alone to effectively manage a patient's MM and severe neutropenia, suggesting a dual therapeutic benefit without treatment-related toxicity. Our findings support the consideration of daratumumab and glucocorticosteroids as a viable first-line therapeutic option for patients with MM who develop neutropenia."

Journal • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Neutropenia • Oncology

EMN39: A Study to Learn How Safe and How Well Linvoseltamab Works Compared to Standard Treatment in Adult Patients With Multiple Myeloma Who Are Not Eligible for Transplant (clinicaltrials.gov) - P3 | N=1000 | Recruiting | Sponsor: European Myeloma Network B.V.

Trial initiation date • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

CC-220-MM-001: A Study to Determine Dose, Safety, Tolerability and Efficacy of CC-220 Monotherapy, and in Combination With Other Treatments in Subjects With Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=466 | Active, not recruiting | Sponsor: Celgene | Trial completion date: Feb 2028 ➔ Jul 2028

Monotherapy • Trial completion date • Hematological Malignancies • Multiple Myeloma • Oncology

PGNMID WITH AKI SUCCESSFULLY MANAGED BY CLONE-DIRECTED THERAPY (ISN-WCN 2026) - "We report a case of PGNMID with severe AKI requiring hemodialysis following recovery from infectious enteritis, successfully managed by clone-directed therapy, including daratumumab and bortezomib.Methods A 60-year-old man presented with proteinuria and edema...He was treated with steroid pulse therapy followed by oral prednisolone and an ARB, later combined with cyclosporine and an SGLT2 inhibitor, achieving partial remission...Prospective studies are essential to establish optimal treatment strategies for PGNMID with AKI. The current case indicates that the narrowing of the glomerular capillary lumina, resulting from an increase in inflammatory cells and mesangial matrix expansion, may lead to AKI."

Gastrointestinal Disorder • Glomerulonephritis • Infectious Disease • Lupus Nephritis • Nephrology • Novel Coronavirus Disease • Renal Disease

LIGHT CHAIN PROXIMAL TUBULOPATHY ASSOCIATED WITH CONCOMITANT FANCONI AND NEPHROTIC SYNDROMES IN A PATIENT WITH MULTIPLE MYELOMA (ISN-WCN 2026) - "Bortezomib and dexamethasone therapy was initiated, followed by daratumumab-based regimens. Conclusion This case suggests that LCPT can present with nephrotic-range proteinuria, presumably due to a combination of light chain overflow and impaired tubular reabsorption, even in the absence of glomerular involvement.This abstract includes content previously presented at "The Japanese Society of Internal Medicine, Koto-Hajime 2025 (Osaka, Japan)". Re-submission to WCN 2026 is permitted by the organizers of the original meeting."

Clinical • Glomerulonephritis • Hematological Disorders • Hematological Malignancies • Immunology • Multiple Myeloma • Nephrology • Renal Disease • Scleroderma • Systemic Sclerosis

A CASE OF ANTI-NEPHRIN AUTOANTIBODIES POSITIVE FSGS RECURRING IMMEDIATELY AFTER KIDNEY TRANSPLANTATION, WITH DARATUMUMAB ADMINISTRATION FAILING TO PREVENT RENAL FUNCTION LOSS (ISN-WCN 2026) - "Treatment with steroids, rituximab (RTX), and LDL apheresis, but treatment was unsuccessful. Hemodialysis started on July 13, and the patient was admitted to the hospital on November 7 for living donor kidney transplantation.In addition to RTX, Basiliximab, mycophenolate mofetil, and tacrolimus, as well as plasma exchange and IVIG...This may be due to the already lost renal function or the possibility of antibody leakage via low-selectivity proteinuria. Japan Renal Transplantation Physician Association"

Clinical • Chronic Kidney Disease • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Inflammation • Transplantation

PLASMA CELL-RICH ACUTE REJECTION IN A YOUNG KIDNEY TRANSPLANT PATIENT AND THE ROLE OF ANTI-CD38 THERAPY (ISN-WCN 2026) - "The maintenance immunosuppressive regimen consisted of cyclosporine, mycophenolate mofetil, and corticosteroids.Five years later, she developed acute kidney injury (creatinine 2.8 mg/dL), accompanied by sub-nephrotic proteinuria (1.5 g/24h), and microhematuria. Our experience suggests that daratumumab may offer a promising therapeutic option to reduce plasma cell infiltration and improve graft outcomes. Further studies are needed to confirm its efficacy and define optimal protocols."

Clinical • IO biomarker • Acute Kidney Injury • Antibody-mediated Rejection • Genetic Disorders • Nephrology • Transplant Rejection • Transplantation

PROSPECTIVE STUDY ON DARATUMUMAB WITH OR WITHOUT AUTOLOGOUS STEM CELL TRANSPLANTATION FOR THE TREATMENT OF MONOCLONAL GAMMOPATHY OF RENAL SIGNIFICANCE (MGRS) DISEASES (ISN-WCN 2026) - "Two patients have undergone ASCT and one more is going to. All ASCT patients had light chain deposition disease (LCDD).Download: Download high-res image (213KB)Download: Download full-size imageConclusion The study will provide important data on the effectiveness of daratumumab either alone or in combination with ASCT in the treatment of both kidney and hematological conditions on various MGRS diseases.I have potential conflict of interest to disclose.Grant from Janssen-Cilag to conduct the study.I did not use generative AI and AI-assisted technologies in the writing process."

Clinical • Amyloidosis • Complement-mediated Rare Disorders • Glomerulonephritis • Hematological Malignancies • Lupus Nephritis • Monoclonal Gammopathy • Multiple Myeloma • Nephrology • Renal Disease • Smoldering Multiple Myeloma • Transplantation

A rare case of renal cancer with PLA2R-positive membranous nephropathy and AL amyloidosis: Insights into mechanisms and treatment. (PubMed, Clin Nephrol) - "The patient achieved remission following sequential treatment with bortezomib, dexamethasone, daratumumab, and rituximab. Future research should focus on the immunological mechanisms of PLA2R antibody production in malignancy and the pathophysiological links among these conditions. Clinicians should remain vigilant for secondary causes of nephrotic syndrome in renal malignancy patients and adopt comprehensive, multidisciplinary approaches to improve outcomes."

Journal • Amyloidosis • Clear Cell Carcinoma • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Glomerulonephritis • Kidney Cancer • Lupus Nephritis • Nephrology • Oncology • Renal Cell Carcinoma • Renal Disease • Solid Tumor

Phase 3 Randomized Study of Daratumumab (DARA) + Bortezomib, Lenalidomide and Dexamethasone (VRd) Versus Alone in Patients with Transplant-Ineligible Newly Diagnosed Multiple Myeloma or for Whom Transplant Is Not Planned As Initial Therapy: Analysis of Minimal Residual Disease in the Cepheus Trial (ASH 2024) - "Of patients who achieved MRD-negativity (10–5) with D-VRd, >80% were alive and progression-free at 54 months. These data further support the use of D-VRd as a new standard of care for patients with NDMM that are TIE or for whom transplant is deferred."

Clinical • Minimal residual disease • P3 data • Residual disease • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Randomized, multi-center study of carfilzomib, lenalidomide, and dexamethasone (KRd) with or without daratumumab (D) in patients with newly diagnosed multiple myeloma (NDMM): The ADVANCE clinical trial. (ASCO 2025) - P2 | "In this large randomized, multicenter investigator-initiated trial for NDMM, treatment with DKRd (59%) compared to KRd (36%) showed a significant, 2.5-fold higher MRD negativity rate with no new safety concerns. Updated EFS, PFS and OS results will be presented at the meeting. Based on these results, DKRd should be a new standard for most NDMM patients receiving initial KRd-backbone therapy."

Clinical • Acute Kidney Injury • Back Pain • Cardiovascular • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Musculoskeletal Diseases • Musculoskeletal Pain • Nephrology • Neutropenia • Novel Coronavirus Disease • Oncology • Orthopedics • Pain • Pneumonia • Pulmonary Disease • Renal Disease • Respiratory Diseases • Septic Shock

Health-related quality of life with belantamab mafodotin in patients with relapsed or refractory multiple myeloma (RRMM): An exploratory analysis of overall quality of life in dreamm-7 (ASH 2025) - P3 | "In DREAMM-7 (NCT04246047), belamaf with bortezomib and dexamethasone (BVd) significantlyprolonged progression-free survival and overall survival vs daratumumab, bortezomib, anddexamethasone (DVd) in patients with RRMM who received ≥1 prior line of therapy. Despite being common with belamaf, ocular events did not have a meaningful impact onHRQOL. Notably, in patients with bilateral worsening of BCVA to 20/50 or worse, HRQOL was maintained,likely due to the transient nature of ocular events and their management with dose reductions anddelays, which have been shown to improve tolerability while maintaining efficacy. The significant efficacybenefits of belamaf prolonged time to deterioration in disease-specific symptoms and physicalfunctioning, including self-care and walking."

Clinical • HEOR • Hematological Malignancies • Multiple Myeloma

Teclistamab plus Daratumumab in Relapsed or Refractory Multiple Myeloma. (PubMed, N Engl J Med) - P3 | "In patients with multiple myeloma who had received one to three previous lines of therapy, those in the teclistamab-daratumumab group had significantly longer progression-free survival than those in the DPd or DVd group. (Funded by Johnson & Johnson; ClinicalTrials.gov number, NCT05083169.)."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology

Multiple Myeloma and Mimicry: Gastrointestinal Tract Histologic Findings in Patients Following Chimeric Antigen Receptor T-cell Therapy and Anti-CD38 Monoclonal Antibodies. (PubMed, Mod Pathol) - "Our findings suggest that CAR-T cell therapy causes gastrointestinal injury characterized by epithelial cell apoptosis and intraepithelial lymphocytosis and predominantly affects crypts and glands in the deep mucosa. Recognizing this pattern may help pathologists suggest the presence of CAR-T cell therapy-induced injury in the appropriate clinical context."

Journal • B Cell Lymphoma • Cytomegalovirus Infection • Dermatology • Diffuse Large B Cell Lymphoma • Gastroenterology • Gastrointestinal Disorder • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • CD19

Long-term progression-free survival benefit with ciltacabtagene autoleucel in standard-risk relapsed / refractory multiple myeloma (ASH 2025) - P1/2, P3 | "Introduction: The CARTITUDE-4 study (NCT04181827), which enrolled patients with lenalidomide-refractory multiple myeloma (MM) after 1–3 prior lines of therapy (pLOT), demonstrated a significantbenefit of ciltacabtagene autoleucel (cilta-cel) over established triplet regimens...Here, we report outcomes inpatients with standard-risk cytogenetics from the intent-to-treat and as-treated populations inCARTITUDE-4. In CARTITUDE-4, patients randomized to the cilta-cel arm underwent apheresis and bridgingtreatment with either pomalidomide, bortezomib, and dexamethasone (PVd) or daratumumab,pomalidomide, and dexamethasone (DPd), followed by lymphodepletion therapy with cyclophosphamideand fludarabine, and then a single cilta-cel infusion... The PFS rate at 2.5 years for patients with standard-risk RRMM was higher in CARTITUDE-4compared with CARTITUDE-1, supporting the use of cilta-cel as early as second line in the treatmentcourse. In CARTITUDE-4 (as-treated..."

Hematological Malignancies • Multiple Myeloma

Phase 3 randomized study of teclistamab plus daratumumab versus investigator's choice of daratumumab and dexamethasone with either pomalidomide or Bortezomib (DPd/DVd) in patients (Pts) with relapsed refractory multiple myeloma (RRMM): Results of majestec-3 (ASH 2025) - P3 | " Eligible pts had 1-3 prior LOTs including a PI and lenalidomide (Len; pts with 1 prior LOT must have been Len-refractory) with progressive disease (PD) on or after the last LOT. We demonstrate the clinically remarkable and statistically significant PFS and OS benefits of Tec-Dara vs SoC triplets in RRMM, with 83.4% of Tec-Dara pts alive and progression-free at 3 yrs. Infections with Tec-Dara were well managed with established protocols. This highly effective, off-theshelf, immunotherapy combination represents a new SoC for RRMM as early as first relapse."

Clinical • IO biomarker • Late-breaking abstract • P3 data • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Plasmacytoma

A phase 2 trial of iberdomide, carfilzomib, daratumumab and dexamethasone quadruplet therapy for relapsed/refractory multiple myeloma: The rekindle study (ASH 2025) - P2 | "In this context, Iberdomide is a potent cereblon E3 ligase modulator (CELMoD)with demonstrated activity in IMiD-resistant disease (Lonial et al., Lancet Haematology. This quadruplet reinduction strategy adds another treatment alternative in the early relapsesetting (i.e., following lenalidomide resistance; 1-3 prior lines) where parenteral (SC or IV) T-cellredirecting therapies are gaining increased prominence. IberKDd is safe with a manageable toxicityprofile, and it affords the opportunity for de-escalation to oral monotherapy; decreasing the burden ofcontinuous parenteral therapy which is common in this setting of MM."

P2 data • Cardiovascular • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukopenia • Multiple Myeloma • Myocardial Infarction • Neutropenia • Respiratory Diseases • Targeted Protein Degradation • Thrombocytopenia • CRBN

Daratumumab-based quadruplet for patients with extramedullary multiple myeloma: Results from the Phase II prospective EMN19 study. (PubMed, Hemasphere) - "The prospective, Phase II EMN19 study assessed the efficacy and safety of daratumumab plus bortezomib, cyclophosphamide, and dexamethasone (DaraVCD) in 40 patients with newly diagnosed MM (NDMM; n = 29) or at first relapse (RMM; n = 11) and positron emission tomography or computed tomography (PET/CT)-confirmed extramedullary plasmacytomas (extraosseous [EMD] and/or paraosseous [PS]). DaraVCD showed encouraging efficacy in patients with MM and extramedullary plasmacytomas. Notably, this is the first report on CTC levels in EMD, and they were lower than previously reported NDMM thresholds."

Journal • P2 data • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Plasmacytoma

Target antigen and plasma cell phenotype are critical factors for sensitivity to response-adapted daratumumab therapy. (PubMed, Blood) - P2 | "Here, patients achieving a partial response (PR) after 2 cycles continued daratumumab, otherwise lenalidomide or bortezomib was added. To our knowledge, this is the first study to demonstrate the effectiveness of response-adapted daratumumab treatment and describe critical biomarkers of single-agent daratumumab sensitivity in vulnerable, therapy naïve MM patients. NCT04151667."

IO biomarker • Journal • Hematological Malignancies • Multiple Myeloma • Oncology • KRAS

Teclistamab Treatment Followed by Heart Transplantation for Advanced Immunoglobulin Light Chain Amyloid Cardiomyopathy. (PubMed, JACC Case Rep) - "Teclistamab achieved a rapid minimal residual disease-negative complete response within weeks, demonstrating its potential as a fast-acting salvage therapy capable of restoring heart transplant eligibility in advanced cardiac AL amyloidosis."

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Hematological Disorders • Transplantation

Daratumumab and belimumab for patients with neutralising anti-interferon-γ autoantibodies mediated adult-onset immunodeficiency: a case series (ESCMID Global 2026) - No abstract available

Clinical • IFNG

Bortezomib, melphalan, and prednisone with or without daratumumab in transplant-ineligible patients with newly diagnosed multiple myeloma (ALCYONE): final analysis of an open-label, randomised, multicentre, phase 3 trial. (PubMed, Lancet Oncol) - P3 | "With more than 7 years of follow-up, D-VMP continued to elicit clinical benefits in transplant-ineligible patients with newly diagnosed multiple myeloma, supporting the efficacy and safety of frontline daratumumab-based therapy in this patient population."

Journal • P3 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Cardiovascular • Endocrine Cancer • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Multiple Myeloma • Myocardial Infarction • Neutropenia • Oncology • Pneumonia • Pulmonary Embolism • Respiratory Diseases • Solid Tumor • Thrombocytopenia • Transplantation