Darzalex Faspro (daratumumab and hyaluronidase-fihj) / J&J, Genmab, Halozyme - LARVOL DELTA

CHARACTERIZATION OF IMMEDIATE ADVERSE EVENTS ASSOCIATED WITH SUBCUTANEOUS DARATUMUMAB AND PREMEDICATIONS (MASCC-ISOO 2025) - "Premedications administered were similar between the first and fourth exposures (dexamethasone: 92.1% vs. 97.3%; acetaminophen: 98.6% vs. 96%; diphenhydramine: 96% vs. 90.7%), except for montelukast (100% vs. 2.6%). Conclusions Daratumumab IRRs were generally mild and primarily occurred with the first exposure. Although the reported incidence of premedication adverse events was relatively low, the absence of IRRs after the second exposure may suggest the feasibility of premedication de-escalation, although further studies are warranted."

Adverse events • Hematological Malignancies • Multiple Myeloma • Oncology

DARZALEX (daratumumab) receives the first positive CHMP opinion for patients with high-risk smouldering multiple myeloma (The Manila Times) - "Janssen-Cilag International NV, a Johnson & Johnson company, today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended the approval of a new indication for DARZALEX (daratumumab) subcutaneous (SC) formulation as monotherapy for the treatment of adult patients with smouldering multiple myeloma (SMM) at high-risk of developing multiple myeloma....The CHMP recommendation is supported by data from the Phase 3 AQUILA study (NCT03301220), evaluating the efficacy and safety of fixed-duration monotherapy daratumumab SC compared with active monitoring in those with high-risk SMM."

CHMP • Multiple Myeloma

DARATUMUMAB-BASED TREATMENTS IN STAGE IIIB AL AMYLOIDOSIS: REAL LIFE EXPERIENCE FROM ANCONA TERTIARY CENTER (EHA 2025) - "Frontline therapy was Dara-CyBorD in 16 patients (42%), CyBorD in 17 (45%), bortezomib-dexamethasone in 3 (8%), melphalan-prednisone in 1 (3%) and rituximab-CyBorD in 1 (3%)... In conclusion, despite small sample size, our real life data showed that, by adding dara to CyBorD, outcome of advanced stage cardiac amyloidosis was not improved since early mortality, mostly due to heart failure, is still the major problem. Pending therapies able to eliminate pre-existing amyloid fibrils, early diagnosis represents the best tool to improve outcome of pts with cardiac amyloidosis, so far."

Clinical • Amyloidosis • Cardiac Amyloidosis • Cardiovascular • Congestive Heart Failure • Heart Failure • Infectious Disease • Novel Coronavirus Disease • Oncology • Pneumonia • Proteinopathy • Respiratory Diseases • Septic Shock

SHORT-TERM RESPONSE AND SAFETY OF DARATUMUMAB TREATMENT IN ADULT IMMUNE THROMBOCYTOPENIA: RESULTS OF A PHASE II STUDY WITH SAFETY RUN-IN (THE DART STUDY) (EHA 2025) - P2 | "Main inclusion criteria: adults (age ≥18) with primary ITP and platelet count of ≤30X109/L (15-30x109/L for the safety run-in) with failure of corticosteroid therapy and at least one second-line therapy, including rituximab and/or TPO- RA. Participants on concomitant ITP treatment were to remain on a stable dose of corticosteroids and/or TPO-RAs during the 2 weeks preceding the inclusion without dose escalation during the study.In the safety run-in phase of the study, 3 patients received 4 weekly subcutaneous daratumumab injections, 1800 mg each, followed by a 4-week observation period... Treatment with daratumumab in ITP patients shows promising results with an acceptable safety profile."

Clinical • P2 data • Acute Kidney Injury • Hematological Disorders • Hematological Malignancies • Immune Thrombocytopenic Purpura • Immunology • Infectious Disease • Novel Coronavirus Disease • Renal Disease • Respiratory Diseases • Thrombocytopenia • Thrombocytopenic Purpura

A REAL-WORLD RETROSPECTIVE-PROSPECTIVE ANALYSIS OF SECONDARY IMMUNODEFICIENCY AND RISK OF INFECTION IN PATIENTS WITH AL AMYLOIDOSIS TREATED WITH DARATUMAMAB-BASED INDUCTION REGIMENS. A MULTICENTER ITALIAN EXPERIENCE (EHA 2025) - "D in combination with Cyclophosphamide, Bortezomib and Dexamethasone is now the standard frontline treatment (Tx) of AL, based on the results of the ANDROMEDA trial... In conclusion, in pts treated with D-based induction the rate of severe Inf is low, despite severe HG affecting more than half of pts at Tx initiation and/or during subsequent Tx, to a large extent secondary to Ig urinary loss. Assessment of risk factors (age, disease burden, s-albumin) may help inform the decision on IgRT in this setting."

Real-world • Real-world evidence • Retrospective data • Amyloidosis • Glomerulonephritis • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Nephrology • Oncology • Pneumonia • Renal Disease • Respiratory Diseases • Septic Shock

THE EFFICACY AND SAFETY OF DARATUMUMAB-BASED REGIMENS IN THE INITIAL TREATMENT OF AMYLOID LIGHT-CHAIN AMYLOIDOSIS (EHA 2025) - "Daratumumab combination therapy regimens included the VCD (bortezomib, cyclophosphamide, and dexamethasone), VD (bortezomib and dexamethasone), ID (ixazomib and dexamethasone), RD(lenalidomide and dexamethasone), PD (pomalidomide and dexamethasone), MP (melphalan and dexamethasone), and MTD regimens (melphalan, thalidomide, and dexamethasone).Patients underwent a median of 7 treatment cycles (range: 2-12), with a hematologic overall response rate (ORR), complete response (CR) rate, median time to response (TTR), and median time to maximal response (TMR) of ≥95.4%, 47.7%, 40 days, and 90 days, respectively... In the present study, Daratumumab-based regimens rapidly induce high-level hematologic responses in , significantly surpassing conventional chemotherapy regimens in cardiac and renal response rates and response speed. The treatment was well-tolerated by patients, and there were no unintended adverse reactions observed outside of clinical trials and no cases of..."

Clinical • Amyloidosis

DARATUMUMAB + BORTEZOMIB/LENALIDOMIDE/DEXAMETHASONE IN TRANSPLANT-ELIGIBLE NEWLY DIAGNOSED MULTIPLE MYELOMA: ANALYSIS OF SUSTAINED MINIMAL RESIDUAL DISEASE NEGATIVITY IN THE PHASE 3 PERSEUS TRIAL (EHA 2025) - P3 | "The phase 3 PERSEUS trial (NCT03710603) evaluated subcutaneous daratumumab plus bortezomib, lenalidomide, and dexamethasone (DVRd) induction/consolidation + DR maintenance vs VRd induction/consolidation + R maintenance in transplant-eligible newly diagnosed multiple myeloma (NDMM). In transplant-eligible NDMM, nearly two-thirds of patients treated with DVRd induction and DR maintenance achieved ≥12-month sustained MRD negativity, associated with >95% 48-month PFS rate. Moreover, ≥24-month sustained MRD-negativity rates with DVRd were 2.5 times as high as VRd, and functionally high-risk incidence was halved with DVRd vs VRd. Collectively, these data further support the PERSEUS regimen as standard of care for transplant-eligible patients with NDMM."

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

DARATUMUMAB PLUS BORTEZOMIB, LENALIDOMIDE, AND DEXAMETHASONE IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA: SUBGROUP ANALYSIS OF TRANSPLANT-INELIGIBLE PATIENTS IN THE PHASE 3 CEPHEUS STUDY (EHA 2025) - P3 | "Treatment effect was generally consistent across subgroups (Table).Safety profile was consistent with ITT and the known profile for daratumumab subcutaneous and VRd.Summary/ In CEPHEUS TIE patients, the ≥CR rate was 80.6% and overall MRD-negativity rate (10−5) was 60.4%, with ~50% of patients sustaining MRD negativity for ≥1 year. In CEPHEUS TIE patients, the ≥CR rate was 80.6% and overall MRD-negativity rate (10−5) was 60.4%, with ~50% of patients sustaining MRD negativity for ≥1 year. Nearly 70% of patients were alive and progression free at 4.5 years. These subgroup data reinforce the strong efficacy of DVRd in the TIE population."

Clinical • P3 data • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Oncology • Transplantation

REAL-WORLD REASSESSMENT OF PROPOSED CLINICAL TRIAL CRITERIA AND TRANSLATIONAL FEATURES IN HIGH-RISK SMOLDERING MULTIPLE MYELOMA (EHA 2025) - "The phase-3 AQUILA trial recently demonstrated a 5-year PFS benefit of 63.1% for subcutaneous daratumumab versus 40.8% for active monitoring in a population of high-risk SMM patients (pts), defined by BMPC% ≥10% plus either i) serum M-protein ≥30 g/L, ii) IgA subtype, iii) immunoparesis, iv) FLC ratio ≥8 and <100, or v) clonal BMPCs of 50-60%... Improved definition and accuracy of high-risk SMM remain critical challenges in managing pts with precursor plasma cell diseases. Despite its merits, the definition used in the AQUILA trial could not be fully recapitulated in this retrospective real-world analysis from a single academic center in Germany. Future risk models may additionally incorporate translational endpoints."

Clinical • Real-world • Real-world evidence • Hematological Malignancies • Monoclonal Gammopathy • Multiple Myeloma • Oncology • Smoldering Multiple Myeloma • NSD2

HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH TRANSPLANT-INELIGIBLE OR TRANSPLANT-DEFERRED NEWLY DIAGNOSED MULTIPLE MYELOMA (MM) IN THE PHASE 3 CEPHEUS TRIAL (EHA 2025) - P3 | "In MAIA, improvement in HRQoL (including pain) was faster in patients (pts) treated with daratumumab plus lenalidomide and dexamethasone (DRd) vs Rd and was sustained in both arms. In the phase 3 CEPHEUS trial (NCT03652064), minimal residual disease negativity and progression-free survival improved with subcutaneous daratumumab plus bortezomib and Rd (DVRd) vs VRd in pts with newly diagnosed multiple myeloma (NDMM)... DVRd-treated pts in CEPHEUS had improved HRQoL and physical functioning as well as symptom (pain, fatigue, overall disease symptoms) reduction from BL as measured by the EORTC QLQ-C30, -MY20, and EQ-5D-5L VAS. Improvements were similar vs VRd with no apparent differences between arms, indicating no detriment to HRQoL with addition of daratumumab, as reported in other daratumumab clinical trials. The TIE subgroup also showed similar PRO results."

Clinical • HEOR • P3 data • Fatigue • Hematological Malignancies • Multiple Myeloma • Oncology • Pain • Transplantation

Response of FX deficiency to Daratumumab-CyBorD as a new Treatment Standard in AL amyloidosis (ISTH 2025) - "(2) Daratumumab SC plus Cyclophosphamide, Bortezomib, and Dexamethasone (CyBorD) causes rapid and deep hematologic and organ response, but the impact on F X deficiency remains unclear. After three cycles, the patient achieved a striking improvement in her organ function (Tab 2), her FX-activity level raised to 14%, and thus, no more bleeding episodes occurred. (Tab 1) Table or Figure Upload"

Amyloidosis • Cardiovascular • Heart Failure • Hematological Disorders • Monoclonal Gammopathy • Oncology • Pulmonary Disease

MAGNETISMM-5: A Study to Learn About the Study Medicine Elranatamab Alone and With Daratumumab in People With Multiple Myeloma Who Have Received Other Treatments (clinicaltrials.gov) - P3 | N=944 | Recruiting | Sponsor: Pfizer | Active, not recruiting ➔ Recruiting

Enrollment open • Monotherapy • Hematological Malignancies • Multiple Myeloma • Oncology

DVRd…Maintains Quality of Life in Multiple Myeloma (AJMC) - P3 | N=395 | CEPHEUS (NCT03652064) | Sponsor: Janssen Research & Development, LLC | "PROs were evaluated at baseline and then longitudinally throughout treatment: during each 28-day treatment cycle through cycle 8, and then every third cycle until disease progression or discontinuation. PRO instruments included the EORTC QLQ-C30, EORTC QLQ-MY20, and the EQ-5D-5L visual analogue scale (VAS). Baseline PRO compliance exceeded 85% and remained above 81% through cycle 36 in both treatment arms."

P3 data • Multiple Myeloma

Testing the Investigational Medication Combination of Daratumumab and Teclistamab Compared to the Usual Treatment (Daratumumab, Pomalidomide, Dexamethasone or Daratumumab, Carfilzomib, Dexamethasone) for Patients With High-risk Multiple Myeloma Refractory or in First Relapse (clinicaltrials.gov) - P2 | N=80 | Not yet recruiting | Sponsor: National Cancer Institute (NCI) | Initiation date: Jul 2025 ➔ Oct 2025

Trial initiation date • Hematological Malignancies • Multiple Myeloma • Oncology

D-VRd Retains Its Role as a Standard of Care for Transplant-Ineligible Multiple Myeloma (OncLive) - P3 | N=395 | CEPHEUS (NCT03652064) | Sponsor: Janssen Research & Development, LLC | "The addition of daratumumab (Darzalex) to bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (D-VRd) led to deeper and more durable responses that translated into improved progression-free survival (PFS) compared with VRd alone in transplant-ineligible patients with newly diagnosed multiple myeloma...At a threshold of 10–5, the overall minimal residual disease (MRD)–negative complete response (CR) or better rate was 60.4% with D-VRd vs 39.3% with VRd (OR, 2.37; 95% CI, 1.47-3.80; P = .0004); at a threshold of 10–6, these rates were 45.8% vs 26.9%, respectively (OR, 2.28; 95% CI, 1.40-3.73)."

P3 data • Multiple Myeloma

LINKER-MM2: A Study to Examine the Effects of Novel Therapy Linvoseltamab in Combination With Other Cancer Treatments for Adult Patients With Multiple Myeloma That is Resistant to Current Standard of Care Treatments (clinicaltrials.gov) - P1 | N=317 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Trial completion date: Jan 2033 ➔ Sep 2034 | Trial primary completion date: Mar 2027 ➔ Apr 2028

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

DVRd Improves MRD Negativity…in Multiple Myeloma (AJMC) - P3 | N=395 | CEPHEUS (NCT03652064) | Sponsor: Janssen Research & Development, LLC | "After a median follow-up of 58.7 months, more patients remained on treatment through cycle 36 in the DVRd arm (n=135) compared with the VRd arm (n=106), suggesting greater treatment durability and possibly better tolerability. DVRd therapy demonstrated significantly improved MRD negativity and prolonged PFS, reinforcing its disease-modifying potential in a frontline setting."

P3 data • Multiple Myeloma

A Multicenter, Prospective Study Evaluating the DVd-Lite Regimen (Reduced-Dose Daratumumab-Based Therapy) in Patients with Light-Chain (AL) Amyloidosis (ChiCTR) - P4 | N=110 | Not yet recruiting | Sponsor: West China Hospital of Sichuan University; West China Hospital of Sichuan University

New P4 trial • Amyloidosis

The cost of convenience: Evaluating economic differences in SQ and IV biotherapeutic formulations. (ASCO 2025) - " SQ formulations of Rituximab (Rituxan Hycela), Trastuzumab (Herceptin Hylecta), and Daratumumab (Darzalex Faspro) became available in 2017, 2019 and 2020, respectively. While subcutaneous (SQ) formulations offer convenience and potential clinical and administrative benefits, they generally cost more than their IV counterparts. SQ Daratumumab was more readily adopted possibly due to fewer drug-related reactions, shorter administration duration, patient convenience, and lack of biosimilar options. Despite the higher costs, convenience and patient preference for SQ formulations may justify their use in certain clinical scenarios."

Oncology

Dara VCD: Outcomes of frontline therapy for light-chain amyloidosis. (ASCO 2025) - "Funded by MSK Cancer Center Support Grant/Core Grant Background: Daratumumab, bortezomib, cyclophosphamide, and dexamethasone (Dara-VCD) is an FDA-approved frontline treatment for AL amyloidosis with the ANDROMEDA trial demonstrating significantly improved outcomes... Dara-VCD was an effective frontline therapy with 79% patients achieving ≥ VGPR with frequent organ responses. However, one third of patients required second line therapy, more often in patients with t(11; 14). Despite the association of t(11; 14) with shorter TTNT, OS does not differ, perhaps associated with Venetoclax."

Amyloidosis • Oncology

Subcutaneous daratumumab (Dara) + bortezomib/lenalidomide/dexamethasone (VRd) with Dara + lenalidomide (DR) maintenance in transplant-eligible (TE) patients with newly diagnosed multiple myeloma (NDMM): Analysis of sustained minimal residual disease negativity in the phase 3 PERSEUS trial. (ASCO 2025) - P3 | "In TE NDMM, nearly two-thirds of pts treated with DVRd induction and DR maint achieved ≥12-mo sustained MRD neg, associated with >95% 48-mo PFS rate. Moreover, ≥24-mo sustained MRD neg rates with DVRd were 2.5 times as high as VRd, and FHR incidence was halved with DVRd vs VRd. Collectively, these data further support the PERSEUS regimen as standard of care for TE NDMM."

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

Daratumumab plus bortezomib, lenalidomide, and dexamethasone (DVRd) in patients with newly diagnosed multiple myeloma (NDMM): Subgroup analysis of transplant-ineligible (TIE) patients in the phase 3 CEPHEUS study. (ASCO 2025) - P3 | "Funded by Johnson & Johnson Clinical Trial Registration Number: NCT03652064 Background: After readout of the PERSEUS and CEPHEUS trials, daratumumab-based therapy + VRd is emerging as the standard of care in NDMM treatment. In CEPHEUS TIE pts, the ≥CR rate was 80.6% and overall MRD neg rate (10−5) was 60.4%, with ~50% of pts sustaining MRD neg for ≥1 y. Nearly 70% of pts were alive and progression free at 4.5 y. These subgroup data reinforce the strong efficacy of DVRd in the TIE population."

Clinical • P3 data • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Oncology • Transplantation

S2209: Comparing Combinations of Drugs to Treat Newly Diagnosed Multiple Myeloma (NDMM) When a Stem Cell Transplant is Not a Medically Suitable Treatment (clinicaltrials.gov) - P3 | N=510 | Recruiting | Sponsor: SWOG Cancer Research Network | Trial completion date: Apr 2030 ➔ May 2031 | Trial primary completion date: Mar 2030 ➔ May 2031

Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

A Study Evaluating Safety, Tolerability, and Clinical Activity of Forimtamig-Based Treatment Combinations in Participants With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=19 | Active, not recruiting | Sponsor: Hoffmann-La Roche | N=316 ➔ 19

Enrollment change • Hematological Malignancies • Multiple Myeloma • Oncology

Additional data from Phase 3 CEPHEUS study explore the benefits of daratumumab SC in transplant-ineligible patients across cytogenetic risk status (GlobeNewswire) - P3 | N=395 | CEPHEUS (NCT03652064) | Sponsor: Janssen Research & Development, LLC | "At a median follow-up of 58.7 months, patients receiving daratumumab-VRd achieved markedly higher overall MRD negativity rates at the 10⁻⁵ sensitivity threshold with 60.4 percent vs 39.3 percent with VRd (OR, 2.37; 95 percent CI, 1.47–3.80; p=0.0004). Furthermore, treatment with daratumumab-VRd resulted in high MRD-negativity rates at the 10⁻⁶ threshold with 45.8 percent compared to 26.9 percent with VRd (OR, 2.28; 95 percent CI, 1.40–3.73; p=0.0010). These deeper responses translated into improved long-term outcomes, with 69.0 percent of patients remaining progression-free at 54-months when treated with daratumumab-VRd vs 48.0 percent with VRd (HR, 0.51; 95 percent CI, 0.35–0.74; p=0.0003)."

P3 data • Multiple Myeloma