bortezomib / Generic mfg. - LARVOL DELTA

Dexamethasone dose intensity does not impact outcomes in newly diagnosed multiple myeloma: a secondary SWOG analysis. (PubMed, Blood) - P1/2, P3 | "We conducted a secondary pooled analysis of the S0777 and S1211 SWOG studies of NDMM, which employed lenalidomide-dexamethasone (Rd) alone with or without bortezomib (VRd) and with or without elotuzumab (Elo-VRd). Given dexamethasone's many toxicities and unclear benefit in the era of modern treatment regimens, dexamethasone dose reduction during NDMM induction warrants further prospective study. NCT00644228, NCT01668719."

Journal • CNS Disorders • Diabetes • Hematological Disorders • Hematological Malignancies • Insomnia • Multiple Myeloma • Oncology • Sleep Disorder • Thrombocytopenia

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

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

High-dose busulfan-melphalan vs melphalan and reinforced VRD for newly diagnosed multiple myeloma: a phase 3 GEM trial. (PubMed, Blood) - P3 | "We compared BUMEL vs. MEL200 outcomes in newly diagnosed multiple myeloma (NDMM) patients receiving intensified bortezomib, lenalidomide and dexamethasone (VRD) induction and consolidation therapy. After a median follow-up of 8.4 years, GEM2012 reported one of the longest PFS durations in NDMM patients, with BUMEL significantly favoring advanced ISS stages. The trial is registered at ClinicalTrials.gov (NCT01916252) and EudraCT (2012-005683-10)."

Journal • P3 data • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Efficacy and safety of a fully human BCMA CAR T-cell therapy for high-risk newly diagnosed transplant-ineligible multiple myeloma: Updated results from an open label, single-arm,phase 1 study(fumanba-2) (ASH 2025) - P1 | "Pts would undergo 4 cycles ofinduction chemotherapy based on one of three regimens: Bortezomib-Lenalidomide-Dexamethasone,Bortezomib-Cyclophosphamide-Dexamethasone, or Bortezomib-Adriamycin-Dexamethasone...After lymphodepletion with Fludarabine-Cyclophosphamide, pts received a single infusion of Eque-cel at the dose of 1.0 x 106 CAR-T cells/Kg.Primary endpoint was the proportion of minimal residual disease (MRD)-negative (MRD−; sensitivity <10-5) and progression-free survival (PFS)...Soluble BCMA was cleared within 1 month post infusion in 81.25% (13/16) of pts.Secretion of inflammatory cytokines was also observed, with median peak levels of 58.59 pg/mL (range:9.12-3017.83 pg/mL) for IL-6, 44.30 mg/L (range: 3.66-117.30 mg/L) for CRP, and 553.35 ng/mL (range:68.10-2349.00 ng/mL) for ferritin.In conclusion, the current data suggest that Eque-cel could be a promising and effective treatment optionfor high-risk NDMM pts following induction therapy. However, longer..."

CAR T-Cell Therapy • Clinical • P1 data • CNS Disorders • Hematological Disorders • Hematological Malignancies • Infectious Disease • Influenza • Multiple Myeloma • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • Transplantation • IL6

A dual targeting BCMA and CD19 fastcar-t (GC012F/AZD0120) as first-line therapy for newly diagnosed multiple myeloma (ASH 2025) - P1, P1/2 | "Here, we report the combined data of these twostudies to provide long term follow up data of GC012F/AZD0120 in NDMM pts.Methods Eligible NDMM pts received a single infusion of GC012F/AZD0120 following two cycles lenalidomide,bortezomib and dexamethasone (RVd) induction therapy...GC012F/AZD0120 was administered at 4 dose levels:1x105/kg (n=1), 1.5x105/kg (n=3), 2x105/kg (n=4), or 3x105/kg (n=22) after a standard 3-daylymphodepletion regimen of fludarabine and cyclophosphamide...3 pts were treated with one dose of tocilizumab and 1 pt was treated with one dose oftocilizumab and corticosteroids...These promising results highlight the potential ofGC012F/AZD0120 CAR-T therapy for treating NDMM patients with HR features and transplant ineligibleNDMM pts. Further research with a larger patient population and extended follow-up is needed tovalidate these findings and address this critically unmet medical need."

Clinical • Hematological Malignancies • Inflammation • Multiple Myeloma • Plasmacytoma • PLAAT3

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

Double hit ultra-high risk myeloma treated with isatuximab, bortezomib, lenalidomide, dexamethasone and cyclophosphamide (Isa-VRDc) induction and isa-VRD consolidation: Initial results of the UK myeloma research alliance (UKMRA) RADAR trial in newly diagnosed transplant eligible patients (ASH 2025) - "RADAR HRv4 pathway is the largest analysis of ultra-high risk (double hit) patients reportedto date. All participants meet the new IMS/IMWG HR criteria. Isa-VRDc induction, followed by Isa-VRDconsolidation post-ASCT and IsaR maintenance met the primary endpoint, with the study crossing theGreen design threshold, with 88% (59/67) alive and progression-free at 18 months."

Clinical • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Transplantation

Effectiveness of bridging therapy corresponds to improved outcomes after ciltacabtagene autoleucel: Phase 3 CARTITUDE-4 study of patients with relapsed, lenalidomide-refractory multiple myeloma (ASH 2025) - "Patients in the cilta-cel arm underwent apheresis, received at least 1 cycle of bridging therapy(investigator's choice) with either pomalidomide, bortezomib, and dexamethasone (PVd) ordaratumumab, pomalidomide, and dexamethasone (DPd), lymphodepletion (cyclophosphamide andfludarabine), and then a single cilta-cel infusion 5–7 days after the start of lymphodepletion. In patients from CARTITUDE-4, better response to bridging therapy correlated with longerPFS and OS. No MNTs were observed in patients who achieved PR or greater following bridging therapy.Patients with poorer responses to bridging therapy were more likely to develop fatal infections,prolonged thrombocytopenia and neutropenia, and had higher rates of non-relapse mortality followingcilta-cel infusion. These data emphasize the importance of optimizing bridging therapy for diseasecontrol prior to receiving cilta-cel."

Clinical • P3 data • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Thrombocytopenia

Primary analysis of the phase 3 randomized trial of selinexor and lenalidomide versus lenalidomide alone as maintenance therapy post autologous stem cell transplant for patients with newly diagnosed multiple myeloma (ALLG MM23; SEALAND) (ASH 2025) - P3 | "Introduction:Selinexor (S) is an oral selective exportin 1 inhibitor approved in relapsed multiple myeloma (MM) incombination with bortezomib (V) and dexamethasone (d)...Patients received ondansetron 8mg immediately prior to, and 8-hours following each S dose.Additional ondansetron and low-dose olanzapine were used as required for break-through nausea andvomiting...In this randomized phase III study, the addition of low-dose S to R maintenance following ASCT did notresult in a significant PFS benefit compared to R alone in NDMM. Although a higher CR rate was observedwith SR, this came at the cost of increased toxicity, including more infections, cytopenias andgastrointestinal AEs. Quality of life, as assessed by EORTC QLQ-C30 and MY20, was comparable betweenarms."

Clinical • P3 data • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Thrombocytopenia • Transplantation • XPO1

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

Final Results of randomized Phase II study of daratumumab, ixazomib, and dexamethasone (DId, ARM A) vs daratumumab, bortezomib and dexamethasone (DVd) followed by daratumumab, did (Arm B) in newly diagnosed multiple myeloma (DeRIVE) study (ASH 2025) - "This is one of the first studies showing the safety and efficacy of non-IMID baseddaratumumab-combination induction therapies with in-class transition of bortezomib to ixazomib (ArmB) yielding higher response rates post-induction and post-transplant without compromising on thesafety. This translated to PFS and OS benefit as well with no survival events for Arm B with more than 60month follow up."

Clinical • P2 data • Esophageal Adenocarcinoma • Esophageal Cancer • Genito-urinary Cancer • Hematological Malignancies • Multiple Myeloma • Prostate Cancer • Solid Tumor

Updated results from the frailty-stratified, randomised controlled bayesian adaptive trial of bortezomib versus lenalidomide in transplant ineligible myeloma (TI NDMM) – the FRAIL-m study (AMaRC 19-01; ALLG MM22) (ASH 2025) - P1/2 | "Lenalidomide (R), bortezomib (V) and dexamethasone (d)are available, but no direct comparisons of VRd vs Rd vs Vd exist to rationalise treatment selection orestablish the standard of care for TI NDMM pts (60% of all NDMM diagnoses). All arms demonstrate acceptable efficacy however, in the triplet (VRd) regimen arms toxicityis emerging in 2A and may be unacceptable in 3A. The observed rate in jointly evaluable 3A patients doesnot meet BOP2 guideline for discontinuation and thus recruitment to all arms continues. These findingshighlight the impact of therapeutic deliverability, support frailty-adapted therapy and question thebenefit of attempting triplet and even quadruplet induction in the truly frail TI-NDMM."

Clinical • Hematological Malignancies • Multiple Myeloma • Transplantation

An immune-therapeutic salvage strategy for 'functional' high-risk (FHR) multiple myeloma (MM) incorporating iberdomide, isatuximab, and dexamethasone – the IBIS study amarc 20-01. (ASH 2025) - P2 | "Of 50 pts: 28%, 32%, 16%, 12% with 0, 1, 2 or 3 high-risk chromosomal abnormalitiesrespectively; 34% fulfilling IMS2025 high-risk criteria, 54% standard-risk and 12% in whom diagnosticCG/FISH were omitted, 83% received PI-IMID 1L (76% VRd, 3% VRd+chemotherapy, 7% VRd+Selinexor),10% bortezomib-cyclophosphamide-dexamethasone (VCD), 7% lenalidomide-dexamethasone (Rd), 24%ASCT; 10% 1REF to 1L and 90% relapsed after initial response to 1L, of these 72% had ³PR to 1L. In this second planned interim analysis, IB-IS-DEX was well-tolerated, achieved early diseasecontrol and demonstrated promising efficacy in FHR MM. Preliminary ctDNA genomic analyses highlight asubstantial burden of adverse biology, with frequent del(17p), MYC copy number gains, and high cTFamong pts with PD. Updates on survival will be presented at the conference."

CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Infectious Disease • Insomnia • Multiple Myeloma • Neutropenia • Respiratory Diseases • Septic Shock • Sleep Disorder • Squamous Cell Carcinoma

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

Optimizing lenalidomide therapy in renal impairment: analysis of renal response in the prospective REMNANT study in transplant-eligible newly diagnosed multiple myeloma. (PubMed, Blood Cancer J) - "All patients received four 21-day cycles of induction with bortezomib, lenalidomide, and dexamethasone. Four RI patients (5%) experienced worsening renal function; two cases were possibly related to lenalidomide, both reversible. These findings support the safety and efficacy of increased lenalidomide-dosing during induction in TE-NDMM patients with RI, including those with severe impairment."

Journal • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Renal Disease • Thrombocytopenia • Transplantation

Long-Term Follow-Up of Patients With Multiple Myeloma Treated on Earlier Total Therapy Protocols: A Secondary Analysis of 3 Clinical Trials. (PubMed, JAMA Oncol) - P2, P3 | "Combinational chemotherapy and tandem hematopoietic stem cell transplant with the implementation of immunomodulatory drugs (thalidomide, lenalidomide) and proteosome inhibitor (bortezomib) extended therapy. Future studies are needed to evaluate the long-term benefits of newer generation treatments in MM. ClinicalTrials.gov Identifiers: NCT00580372, NCT00083551, NCT00081939."

Clinical • Journal • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Circulating tumor cells predict myeloma outcomes in patients treated with daratumumab, bortezomib, lenalidomide, and dexamethasone. (PubMed, Blood) - P3 | "D-VRd improved overall and sustained MRD-negativity rates in CTC-high and CTC-low patients, and improved PFS for CTC-low with a positive trend in CTC-high patients. NCT03710603."

Circulating tumor cells • Journal • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation • CTCs

Patient-reported outcomes with belantamab mafodotin, pomalidomide, and dexamethasone versus bortezomib, pomalidomide, and dexamethasone in patients with relapsed or refractory multiple myeloma (DREAMM-8): a phase 3, open-label, randomised controlled trial. (PubMed, Lancet Haematol) - P3 | "Patients with relapsed or refractory multiple myeloma treated with belantamab mafodotin, pomalidomide, and dexamethasone or bortezomib, pomalidomide, and dexamethasone reported stable HRQOL. Self-reported ocular adverse events were generally manageable and minimally bothersome within the first year of treatment. These findings indicate that belantamab mafodotin, pomalidomide, and dexamethasone is well tolerated, with little detriment to HRQOL, supporting its use in relapsed or refractory multiple myeloma."

Clinical • Journal • P3 data • Fatigue • Hematological Malignancies • Multiple Myeloma • Oncology

The impact of Duffy genotype on progression-free survival (PFS) with lenalidomide, Bortezomib, and dexamethasone (RVd) alone or RVd plus autologous stem cell transplantation (ASCT) and continuous R maintenance in patients (pts) with newly diagnosed multiple myeloma (NDMM): Updated subgroup analysis of the phase 3 DETERMINATION trial (ASH 2025) - "These exploratory analyses of DETERMINATION suggest that Duffy status drives a differencein tx effect that is more pronounced than for PFS by race. With RVd-alone vs RVd+ASCT, PFS appearedbetter in Duffy null pts and poorer in Duffy non-null pts. In Duffy null vs non-null pts, PFS appeared betterwith RVd-alone and poorer with RVd+ASCT."

Clinical • P3 data • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Neutropenia • Transplantation • ACKR1

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

Efficacy and Safety of Selinexor Combined with VRD in Newly Diagnosed Multiple Myeloma with EMD: A Phase 2 Trial. (PubMed, Blood Adv) - P2 | "This multicenter, open-label, single-arm phase II investigator-initiated trial evaluated selinexor combined with bortezomib, lenalidomide, and dexamethasone (SVRD) in NDMM with EMD. These findings support SVRD as a rational frontline option for EMD-positive NDMM and justify randomized studies to confirm durability and benchmark against contemporary quadruplets and cellular therapies. NCT# NCT05900882."

Journal • P2 data • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Thrombocytopenia

IgE plasma cells localize to secondary and tertiary lymphoid follicles and exhibit elevated ER stress during allergic inflammation in mice (AAAAI 2026) - "Consistent with an increase in protein translation and ER stress, IgE PCs were sensitive to proteosome inhibition and underwent apoptosis when treated with bortezomib. Conclusions Our findings highlight that IgE PCs can localize in spleen and lung during allergic inflammation and have elevated ER stress, which potentially increases their susceptibility to proteasome inhibition."

Preclinical • Inflammation • Respiratory Diseases • Targeted Protein Degradation • DERL1 • EEF1A1

Carfilzomib, lenalidomide, and dexamethasone (KRd) versus bortezomib, lenalidomide and dexamethasone (VRd) in patients with newly diagnosed multiple myeloma (NDMM) – interim results from the randomized Phase III COBRA trial. (ASH 2025) - P3 | "The randomized phase III COBRA trial showed superior efficacy of KRd compared VRd in NDMM, withsafety profile consistent with prior reports. These findings support further evaluation of KRd-basedinduction regimens in NDMM."

Clinical • P3 data • P3 data: top line • Bone Marrow Transplantation • Infectious Disease • Multiple Myeloma • Neutropenia • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

Role of bortezomib maintenance therapy in the anti-CD38 antibody era: Interim analysis results of a randomized Phase III study for transplant-ineligible newly diagnosed multiple myeloma (JCOG1911/B-DASH Study) (ASH 2025) - "Introduction Daratumumab (Dara) plus melphalan, prednisolone, and bortezomib (Bor) (D-MPB), followed by Daramaintenance therapy, has become one of the standard of care for transplant-ineligible (TI) newlydiagnosed multiple myeloma (NDMM) based on the ALCYONE trial. Accordingly, in March 2025, the JCOG's Data and Safety MonitoringCommittee recommended early termination of the study.ConclusionThis phase III study revealed that adding Bor to Dara maintenance therapy did not improve PFS inpatients with TI-NDMM. Tolerability issues, including a high incidence of AEs and frequent treatmentdiscontinuation due to AEs in arm B, as well as favorable PFS exceeding our expectations in arm A, mayhave influenced the results of the JCOG1911."

Clinical • P3 data • P3 data: top line • Cardiovascular • Hematological Malignancies • Hypertension • Infectious Disease • Multiple Myeloma • Respiratory Diseases • Transplantation