belantamab (GSK2857914) / GSK - LARVOL DELTA

Belantamab for the Treatment of Multiple Myeloma: Results from Part 1 of the First-in-Human Phase 1/2 DREAMM-20 Trial (IMS 2025) - P1 | "Introduction: Belantamab mafodotin (belamaf) is a B-cell maturation antigen (BCMA)–targeted monoclonal antibody (mAb) conjugated with a monomethyl auristatin F (MMAF) payload. Belantamab had a favorable safety profile, with no DLTs, TRAEs leading to discontinuation, or grade ≥2 corneal events associated with belantamab. Encouraging preliminary clinical activity was observed, with durable responses occurring across dose levels in this heavily pretreated, triple class−exposed population. These findings support the potential of belantamab to provide clinical activity with an acceptable safety profile."

First-in-human • P1/2 data • Anemia • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Ophthalmology

Preclinical efficacy of a bispecific NK cell engager studied using a humanized multiple myeloma mouse model (AACR 2026) - "Flow cytometry of bone marrow showed fewer BCMA+CD138+ cells, indicating MM cells, in the engager- and belantamab-treated groups compared to vehicle controls.These findings support the potential of the bispecific NK cell engager combined with ADAPT-NK cells as a treatment for MM. The study also demonstrates the utility of the humanized MM mouse model for evaluating NK cell engagers using BLI and flow cytometry."

Bispecific • IO biomarker • Preclinical • Hematological Malignancies • Multiple Myeloma • Oncology • FCGR3A • IL6 • SDC1

Bone marrow from acute myeloid leukemia (AML) and multiple myeloma (MM) patients can be used to evaluate target expression and on-target efficacy for novel antibody drug conjugates (ADCs) (AACR 2026) - "Gemtuzumab ozogamicin (Mylotarg), Belantamab Mofodotin (Blenrep) and Trastuzumab vedotin were evaluated for toxicity to hematopoietic progenitor cells using the colony forming cell assay (CFC) in diseased (on-target efficacy) and normal bone marrow (NBM) (off-target toxicity). Blenrap in MM patient bone marrow had IC50 values which ranged from 4.4 to 46 µg/mL with an average IC50 value of 21 µg/mL, compared to evaluation in NBM which resulted in IC50 values > 30 µg/mL (highest tested concentration) and rarely had any impact on colony growth. These data suggest that the CFC assays with primary normal and diseased bone marrow cells may provide insight as to relative potency of an ADC on a disease-specific target as well as potential off-target toxicity to normal hematopoietic progenitors."

ADC • Clinical • IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology • CD33 • HER-2

Synthbody™- A novel multivalent multispecific antibody drug conjugate platform demonstrates combinatorial logic-gated "synthetic" targeting of cancer antigens with log order enhanced internalization and potency (AACR 2026) - "Antibody Drug Conjugates (ADCs), such as trastuzumab deruxtecan, achieve complete responses >20% and duration of response >30 months in patients with metastatic Her2+ breast cancer1...SDF-061390E (and SDF-061390E-MMAF) demonstrates >30x greater internalization and >80x greater potency when compared, respectively, with the BCMA-targeting antibody Belantamab and Belantamab mafodotin in human myeloma cells...Optimized Synthbody™ constructs show excellent production in CHO cells, developability and IgG-like PK in vivo.The novel Synthbody™ platform demonstrates broad utility as ADC and biologic therapeutics, with capabilities for coordinated targeting, advanced logic-gated control and multifunctional action that may complement or ultimately replace current IgG-based biologics.1 Cortes et al. Nat Med 2024"

ADC • IO biomarker • Breast Cancer • Hematological Malignancies • HER2 Breast Cancer • HER2 Positive Breast Cancer • Multiple Myeloma • Oncology • Solid Tumor • HER-2

Changing the Survival Landscape in RRMM with Novel ADC (ICKSH 2026) - "In the phase 3 DREAMM -7 trial, patients with RRMM after at least one prior line were randomized to belantamab mafodotin plus bortezomib and dexamethasone (BVd) versus daratumumab plus bortezomib and dexamethasone (DVd)...In the phase 3 DREAMM -8 trial, belantamab mafodotin in combination with pomalidomide and dexamethasone (BPd) likewise yielded markedly prolonged progression free survival ( PFS) and higher MRD -negative deep responses compared with the control arm (PVd) , including in clinically relevant subgroups such as patients with lenalidomide -refractory disease and those previously exposed or refractory to anti -CD38 antibodies. Belantamab mafodotin has a distinct toxicity profile, most notably ocular toxicity that is mechanistically linked to the ADC payload and occurs more frequently in belantamab -containing regimens than comparator triplets...In conclusion, the superior efficacy across OS, PFS and DOR in the DREAMM -7 and DREAMM -8 trials supports the..."

Hematological Malignancies • Multiple Myeloma • Ophthalmology

Antibody-Drug Conjugates, T-Cell Engager Bispecific Antibodies and Chimeric Antigen Receptor T Cells for Multiple Myeloma: What's the Current Status? (PubMed, Target Oncol) - "This has resulted in European Medicines Agency and US Food and Drug Administration approval of agents targeting the B-cell maturation antigen: antibody-drug conjugate belantamab mafodotin (belantamab), bispecific T-cell engaging antibodies teclistamab, elranatamab and linvoseltamab, and chimeric antigen receptor T-cell products idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel). Talquetamab, a bispecific T-cell engaging antibody targeting G protein coupled receptor family C group 5 member D has also been approved by the European Medicines Agency and Food and Drug Administration. With increasing availability of these agents, knowledge on the efficacy and safety of these novel treatments will be essential for future multiple myeloma care. In this narrative review, we discuss the pivotal trials, current real-world evidence and recent insights in the mechanisms of resistance of antibody-drug conjugates, bispecific T-cell engaging antibodies and..."

Journal • Review • Hematological Malignancies • Multiple Myeloma • Oncology

DREAMM-20: A Study to Investigate the Safety and Efficacy of Belantamab for the Treatment of Multiple Myeloma When Used as Monotherapy and in Combination Treatments (clinicaltrials.gov) - P1/2 | N=153 | Recruiting | Sponsor: GlaxoSmithKline | Phase classification: P1 ➔ P1/2 | N=55 ➔ 153

Enrollment change • Monotherapy • Phase classification • Hematological Malignancies • Multiple Myeloma • Oncology

Maintenance Therapy with Belantamab, Pomalidomide and Dexamethasone in High-risk Myeloma Patients: A Phase 2 Study with a Safety Run-in - Interim Analysis (IMS 2025) - P2 | "In pts with high-risk myeloma, BPd maintenance deepened responses, with MRD negativity (10-5) attained in 80% of pts. The extended dosing schedule of belantamab 1.9 mg/kg every 12 weeks is not associated with higher grade toxicities and had proven efficacy in this setting. The current results support the exploration of BPd maintenance in future high-risk studies."

Clinical • Late-breaking abstract • P2 data • Cardiovascular • CNS Disorders • Cough • Hematological Malignancies • Inflammation • Insomnia • Multiple Myeloma • Ophthalmology • Pneumonia • Respiratory Diseases • Sleep Disorder

Prophylactic tocilizumab in Relapsed/Refractory multiple myeloma patients treated with bispecific antibodies: A single centre experience (ASH 2025) - "Twelve patients (46%) had received previous anti-BCMA therapy (8 belantamab, 2 both belantamab and teclistamab, 1 teclistamab and 1 idecel). Talquetamab was administered to 16 patients (61%), teclistamab to 8 (30%), elranatamab to 2 (8%)...Premedication for each step up dose included dexamethasone, acetaminophen and diphenhydramine...This data supported, in our center, the use of prophylactic tocilizumab in outpatient setting. Given these results, even if all CRS events were grade 1, remained fully manageable and ICANS were rare, the use of prophylactic tocilizumab could improve treatment safety, inpatient management, and ultimately support feasibility in the outpatient regimen."

Clinical • Hematological Disorders • Hematological Malignancies • Inflammation • Multiple Myeloma • Neutropenia • Thrombocytopenia

Zip-code drug conjugates (ZDCs): Ctdna-guided therapy shows strong efficacy and low toxicity in vitro and In Vivo (ASH 2025) - "Compared to Belantamab (an anti-BCMA MM ADC), KTS002 was 1000-fold more cytotoxic in cells with p53 deletions or mutations...In MM1Sxenograft models, KTS002 demonstrated dose-dependent tumor suppression, with high-dose treatmentoutperforming bortezomib...KTS002 is a promising new therapy for MM, especially in high-risk patients, offering strongefficacy with minimal toxicity. Ongoing studies are focused on dose optimization, pharmacokinetics, andsafety to support IND-enabling and clinical development."

Circulating tumor DNA • IO biomarker • Preclinical • Hematological Malignancies • Multiple Myeloma • FGFR3 • MAFB • NSD2

Impact of previous BCMA exposure: Evidence from practice outside of clinical trials to inform talquetamab sequencing (ASH 2025) - "Within theBCMA exposed group, 41 patients received belantamab, 6 were treated with a BCMA-bispecific antibody,and 5 received BCMA-CAR T. The median time to next treatment of BCMA-exposed patients from BCMAagent to TAL was 4.4 months (CI95% 3.1-5.1): 5 patients BCMA-CART 10.9 months (CI95% 3.5-18.2), 30patients belantamab 3.9 months (CI95% 3-5) and 5 patients BCMA-BsA 4.9 months (CI95% 2.1-7.7). Our study on TAL therapy in a setting comparable to real-world conditions, highlightednoteworthy response rates and survival among both BCMA exposed and naïve groups, though nosignificant differences in progression-free survival or overall survival were observed. These findingsunderscore the potential of TAL in treating BCMA-exposed patients, even though the majority weretreated with BCMA ADC. While the retrospective nature of this study imposes some limitations, theseinsights may be valuable for improving clinical decision-making."

Clinical • Hematological Malignancies • Multiple Myeloma

Trends in Medicare Spending on Multiple Myeloma Drugs, 2013 to 2021 (ASH 2023) - "Lenalidomide (68%) and pomalidomide (52%) had the largest price increases...Spending on the three myeloma drugs approved via accelerated approval but subsequently withdrawn from the market following confirmatory trials was $85,328,842 (melflufen: $859,764, belantamab: $31,749,711, panobinostat: $52,719,367). Spending data demonstrate prescriber sensitivity to route-of-administration-specific toxicities: almost no intravenous bortezomib was prescribed, and in 2021, >60% of patients on daratumumab received subcutaneous Darzalex Faspro. Second-in-class anti-CD38 antibody isatuximab offered daratumumab little competition (623 beneficiaries received isatuximab vs 20,573 receiving daratumumab)...Our analysis underscores why the Inflation Reduction Act—and its key provisions of inflationary rebates and Medicare price negotiation—are vital to rein in Medicare spending. Generic competition, particularly for lenalidomide and bortezomib, whose patents expired recently, may also..."

Medicare • Reimbursement • US reimbursement • Hematological Malignancies • Multiple Myeloma • Oncology

Final Results of Phase 1 Clinical Trial of Belantamab Mafodotin Combined with Carfilzomib, Lenalidomide, and Dexamethasone for Multiple Myeloma after One to Three Prior Lines of Therapy (ASH 2024) - "Moreover, in the DREAMM-8 trial, Belamaf outperformed bortezomib in combination with pomalidomide and dexamethasone...50% of pts with available ISS staging data at diagnosis had stage III, 42% were refractory to lenalidomide, 11% were bortezomib refractory, 26% were double refractory, and 26% were daratumumab refractory...Conclusions : This phase 1 trial established the MTD of belantamab of 1.9 mg/kg every 8 weeks in combination with KRd...Despite the dosing schedule of every 8 week Belamaf dosing, clinically significant keratopathy was common. Pts with high-risk newly diagnosed MM will be enrolled in the phase 2 portion of this trial."

Clinical • P1 data • Cough • Fatigue • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Ophthalmology • Respiratory Diseases • Thrombocytopenia

Phase I/II Study of Belantamab Mafodotin, Cyclophosphamide, and Dexamethasone (BelCyd) in Relapsed/Refractory Multiple Myeloma (ASH 2023) - P1/2 | "Median time since diagnosis was 9 years with a median of 5 prior therapies (range: 4- 7) including Auto-SCT (n=7), Allo-SCT (n=1); all patients had received lenalidomide, pomalidomide, bortezomib, carfilzomib & daratumumab, 2 patients had BCMA CAR T cell therapy. The RP2D of BelCyd is 2. 5 mg/kg Q6W plus Cy 500 mg & dexa 40mg; no new safety signal was seen. BelCyd activate NK, cytotoxic T cells & macrophages adding to Bel direct MM cytotoxicity."

IO biomarker • P1/2 data • Hematological Malignancies • Multiple Myeloma • Oncology • Ophthalmology • Plasmacytoma • B2M • CCL2 • CCL3 • CCR7 • CD14 • CD8 • CSF2 • CXCL10 • GZMB • IFNG • IL13 • IL7 • MRC1 • SDC1 • TGFB1

A Multicenter Phase 2 Study Evaluating the Optimized Schedule of Belantamab Mafodotin 1.9 Mg/Kg Q8W Plus Bortezomib and Dexamethasone in Relapsed Refractory Multiple Myeloma (ASH 2024) - P2 | "Belantamab in combination with bortezomib and dexamethasone (Vd) and belantamab in combination with pomalidomide and dexamethasone (Pd) confirmed significant benefit in PFS over daratumumab Vd and bortezomib Pd, respectively (V Hungria, NEJM 2024; MA Dimopoulos, NEJM 2024). Conclusion : The ocular findings seem to be limited due to the significantly de-escalated belantamab dosing and still the ORR reaches 64% (25/39) with MRD negativity rate of 10% (4/39). The clinical trial is ongoing, these results will have to be confirmed by the final analysis."

Clinical • P2 data • Cardiovascular • Congestive Heart Failure • Heart Failure • Hematological Malignancies • Hepatology • Infectious Disease • Multiple Myeloma • Oncology • Ophthalmology

Outcomes Multiple Myeloma Patients Progressing after BCMA-Directed Chimeric Antigen Receptor T Cell (CART) Therapy (ASH 2023) - "All pts were refractory to PI, IMid, Daratumumab, double-refractory and-triple refractory...Outcomes with next LOT: Of these 30 pts, 10 received BCMA-directed therapies (3 got belantamab mefodotin and 7 received bispecifics (BCMA on Harpoon trial and teclistamab, 2 received GPRC5D targeting bispecific, talquetamab... This study describes outcomes for post-CART relapse in RRMM. Most pts do not respond to the first LOT post-BCMA CART relapse. The survival was less than a year, suggesting need for further studies with a longer follow-up and larger sample size to establish the best regimen for CART failure and characterize prognostic factors associated with poor outcomes for CART relapses."

CAR T-Cell Therapy • Clinical • IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology

Prior Exposure to Belantamab Mafodotin Influences Outcomes with Idecabtagene Vicluecel in Patients with Multiple Myeloma (ASH 2024) - "The incidence and severity of CRS and NT, the average number of days in the hospital and in the ICU, the need for tocilizumab, anakinra, steroids, the incidence and severity of cytopenias, and the need for stem cell boosts did not differ significantly between those with and without prior exposure to belantamab (p > 0.05). Specifically, patients who respond to belantamab exhibit inferior outcomes with ide-cel compared to those not achieving a partial or better response to belantamab. With the potential re-approval of belantamab and the increasing availability of BCMA CAR T-cell therapy, understanding the impact of previous exposure to BCMA-directed therapies is crucial for optimizing treatment selection for these patients."

Clinical • Anemia • Hematological Disorders • Hematological Malignancies • Inflammation • Multiple Myeloma • Neutropenia • Oncology • Ophthalmology • Thrombocytopenia

Epigenetic Silencing of Immunotherapy Targets in Multiple Myeloma (DGHO 2025) - "Known genetic drivers: structural variants (SVs), deletions, single-nucleotide variants (SNVs) in target genes, only account for a minority of resistant cases, suggesting alternative mechanisms e.g. epigenetic ones.We performed long-read Nanopore sequencing on sequential bone marrow samples from patients who relapsed to anti-BCMA (CAR T, elranatamab, belantamab) and anti-FCRL5 therapies (cevostamab). Our findings advocate for the clinical integration of methylation profiling as a predictive and monitoring tool to anticipate resistance. The observations of an "epigenetic resistance memory" argues in favour of a broader, underappreciated role in multidrug resistance."

IO biomarker • Hematological Malignancies • Multiple Myeloma • CRBN • DNMT1 • DNMT3A • DNMT3B

Predictive Markers for Outcomes after Disease Progression Post BCMA-Directed CAR T-Cell Therapy in Patients with Relapsed or Refractory Multiple Myeloma (ASH 2024) - "BACKGROUND Idecabtagene vicleucel (I) and Ciltacabtagene autoleucel (C) are two commercially available BCMA-directed CAR-T cell products initially FDA approved after > 4 lines of therapy in patients with triple class exposed relapsed or refractory multiple myeloma patients (RRMM)...Treatment at progression was categorized as follows : combination therapy (CT including alkylating agents, proteasome inhibitors, immunomodulatory agents, BCL2 inhibitors, XPO1 inhibitors, monoclonal antibodies), BCMA bispecific antibody (teclistamab, elranatamab), GPRC5D bispecific antibody (talquetamab), BCMA antibody-drug conjugate (ADC) (belantamab) and clinical trial...High-risk cytogenetics and high tumor burden at the time of progression are associated with worse outcomes in these patients. The post progression use of either BCMA or GPRC5D bispecific antibody is associated with improved outcomes as compared to combination chemotherapy"

Biomarker • CAR T-Cell Therapy • Clinical • IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology

Real-World Analysis of Teclistamab in 115 RRMM Patients from Germany (ASH 2023) - "35.6% (41/115) had received BCMA-directed pretreatment, among them 20 with ide-cel, 21 with belantamab mafodotin and single patients with both or a BCMA-directed study medication...In the group of patients with BCMA-directed pretreatment, the ORR of belantamab-pretreated patients (70%) was comparable to that in anti-BCMA naïve patients (60.0%), whereas ide-cel pretreated patients showed a significantly lower ORR of 27.8%...Tocilizumab was administered in 25.2% and dexamethasone in 15.7% of patients...Conclusions With an ORR of 56.8% in all patients and 60.0% in anti-BCMA naive patients, Teclistamab showed a similar ORR in the real-world setting to that observed in the MAJESTEC-1 trial. PFS was slightly lower, but our patient collective comprised higher proportions of patients with high risk disease, extramedullary disease, high disease burden, hematopoietic or renal impairment."

Clinical • Real-world • Real-world evidence • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Oncology • Renal Disease

A Real-World Pharmacovigilance Analysis of Cardiac Adverse Events Associated with Newer Antibody-Drug Conjugates: A Disproportionality Analysis from FDA Adverse Event Reporting System Database (ASH 2024) - "Trastuzumab, one of the earliest approved ADCs for breast cancer, is known to cause cardiotoxicity, however, significant cardiac adverse events (CAEs) have not been reported with the recently approved ADCs. We aim to explore the post-marketing reports of CAEs with these medications.Methods : •Drugs of interest : We analyzed gemtuzumab, inotuzumab, polatuzumab, belantamab, and loncastuximab.•Data Source and Extraction : Data was obtained from the publicly available FDA Adverse Event Reporting System (FAERS)...Given the limited exploration in the trial data, there is a broader question of establishing causation between ADCs and CAEs. Findings of our analysis support the need for further post-marketing surveillance and potential inclusion of significant CAEs to the drug labels."

Adverse events • Clinical • Real-world • Real-world evidence • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Atrial Fibrillation • B Cell Lymphoma • Breast Cancer • Cardiomyopathy • Cardiovascular • Diffuse Large B Cell Lymphoma • Heart Failure • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Myocardial Infarction • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • Ventricular Tachycardia

In Vivo Anti-BCMA CAR T-Cell Expansion Kinetics Correlate with Early IMWG Response in RRMM: A Single Institution Study with Comparative Analysis of Idecabtagene Vicleucel and Ciltacabtagene Autoleucel (ASH 2023) - "Seven patients (30.4%) were previously treated with belantamab...Post-CAR T ferritin max correlated with the baseline b2m (p<0.001) and tocilizumab dose number (p=0.009) but none correlated with peak CAR T expansion (p=0.315)... In our single-center study of comparative analysis of commercial BCMA targeting CAR T-cell treatments, peak CAR T-cell expansion showed a positive correlation with +1 and +3 month post-CAR-T clinical responses. Despite the delayed peak expansion with ciltacel, the expansion was more robust with a higher level of circulating CAR T-cells. Baseline ALC or fludarabine dose reduction did not have an impact on overall CAR T expansion in combined cohort."

CAR T-Cell Therapy • Preclinical • Hematological Malignancies • Multiple Myeloma • Oncology • B2M

Real-World Characteristics, Step-up Dosing Patterns, and Outcomes in Patients with Multiple Myeloma Receiving Teclistamab at Texas Oncology Community-Based Treatment Centers (ASH 2024) - "Of the 2 pts (13%) with prior BCMA exposure, both received belantamab; the median time from belantamab to teclistamab initiation was 17.5 months (range : 16.2-18.8).Six pts (40%) received SUD in a TxO outpatient facility; nine (60%) were referred outside of TxO for SUD, all of whom returned to TxO for the first treatment dose...No pts received primary prophylactic tocilizumab for CRS...Nonetheless, these initial outcomes support the feasibility of administering teclistamab using a community-based approach, which is important to ensure access for pts in need of novel therapies. This analysis will be updated with more pts and longer follow-up."

Clinical • Real-world • Real-world evidence • Anemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Oncology • Renal Disease

Dexamethasone Is Associated with Cataracts in Multiple Myeloma Even after Adjusting for Age: Results of a Large Cross-Sectional Survey (ASH 2024) - "Introduction : Many multiple myeloma (MM) therapies can increase the risk of ocular comorbidities such as bortezomib-related blepharitis or belantamab-related keratopathy. Future research is in development to prospectively investigate whether dex reduction strategies can mitigate this longitudinal risk of cataracts. More broadly, our findings suggest that periodic eye exams - although inconsistently recommended by oncologists - are a key component of supportive care for patients living with MM.Funding : HealthTree Foundation through patient donations."

Cataract • Dry Eye Disease • Glaucoma • Hematological Malignancies • Multiple Myeloma • Ocular Inflammation • Oncology • Ophthalmology

Treatment Modalities and Outcomes of Multiple Myeloma Patients with Spinal Cord Compression: A Single Center Experience (ASH 2024) - "9 pts received proteasome inhibitors (PIs) based therapy (8 bortezomib and 1 carfilzomib), 2 pts received chemotherapy (one combined with PIs), and 1 patient each was treated with daratumumab and belantamab. Newly diagnosed pts presenting with SCC have similar OS compared with their "non-SCC" counterparts, whereas pts with SCC event at the time of relapse appear to have dismal prognosis. Failure to achieve a favorable neurological outcome is associated with decreased survival, emphasizing the need for larger clinical trials to guide optimal management and decision-making."

Clinical • Anemia • Cardiovascular • CNS Disorders • Congestive Heart Failure • Gastroenterology • Gastrointestinal Disorder • Heart Failure • Hematological Disorders • Hematological Malignancies • Infectious Disease • Mucositis • Multiple Myeloma • Neutropenia • Oncology • Orthopedics • Plasmacytoma • Thrombocytopenia