melphalan / Generic mfg. - LARVOL DELTA

Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone for the Treatment of High-Risk Newly Diagnosed Multiple Myeloma. (PubMed, J Clin Oncol) - "Isa-KRd effectively induces high rates of sustainable MRD negativity in the difficult-to-treat HRNDMM population, regardless of transplant status, translating into a median PFS that was not yet reached after 44/33 months."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Curative Strategy (GEM-CESAR) for High-Risk Smoldering Myeloma (SMM): Post-Hoc Analysis of Sustained Undetectable Measurable Residual Disease (MRD) (ASH 2022) - "Induction therapy consisted of six 4-weeks cycles of KRd in which carfilzomib (K) was given at dose of 36 mg/m2 twice per week plus lenalidomide (R) at dose of 25 mg on days 1-21 and dexamethasone (d) at dose of 40 mg weekly. Melphalan at dose of 200 mg/m2 followed by ASCT was given as intensification therapy followed by two KRd consolidation cycles and maintenance with R at dose of 10 mg plus dexamethasone at dose of 20 mg weekly for up to 2 years...Patients experiencing biological progression (biochemical or MRD conversion from -ve to +ve) after stopping maintenance had the opportunity of receiving rescue therapy with daratumumab in combination with pomalidomide and dexamethasone (DPd)... Twenty-three percent of high-risk SMM treated with this curative strategy maintained MRD-ve 4 years after ASCT and 2 years after finalizing the treatment protocol. Progression to MM as well as biochemical progression were driven by the persistence of MRD at the end of maintenance and..."

Residual disease • Retrospective data • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Novel Coronavirus Disease • Oncology • Transplantation

Triplet Therapy, Transplantation, and Maintenance until Progression in Myeloma. (PubMed, N Engl J Med) - P3 | "Among adults with multiple myeloma, RVD plus ASCT was associated with longer progression-free survival than RVD alone. No overall survival benefit was observed. (Funded by the National Heart, Lung, and Blood Institute and others; DETERMINATION ClinicalTrials.gov number, NCT01208662.)."

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

Beta-Blocker Use During Plasma Cell-Directed Chemotherapy in Immunoglobulin Light-Chain Cardiac Amyloidosis: A Propensity-Matched Real-World TriNetX Analysis (SOHO 2026) - "Patients or Other Participants: Adults with AL amyloidosis (International Classification of Diseases, 10th Revision, E85.81) and cardiac involvement receiving daratumumab, bortezomib, cyclophosphamide, melphalan, and/or dexamethasone were identified. In patients with AL-CM receiving plasma cell-directed chemotherapy, BB therapy demonstrated a significant time-to-event survival signal despite increased HF hospitalization and AKI. Importantly, BB exposure was not associated with excess hypotension, bradycardia, or syncope, suggesting distinct hemodynamic tolerability in chemotherapy-treated AL-CM and challenging the routine avoidance of BB therapy in this population."

Clinical • Real-world • Real-world evidence • Oncology

Immune-MRD status informs tumor-MRD outcome prognostication in patients with multiple myeloma on lenalidomide maintenance. (PubMed, Clin Cancer Res) - "This "immune-MRD" status showed predictive potential, and segregated patients with MRDres and early disease progression from patients with sustained remission despite MRDres."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Autologous Hematopoietic Cell Transplantation for Multiple Myeloma: Real-World Outcomes From a Single Center in Pakistan (SOHO 2026) - "Daratumumab-based quadruplet was used in 1.6%...Bortezomib-based dual maintenance was used in 25.2% of patients, carfilzomib-based dual maintenance in 18.0%, lenalidomide monotherapy in 42.3%, and other agents in 14.4% of patients... AHCT for MM is feasible in LMICs, producing outcomes comparable to international data. In the absence of diagnostics for risk stratification, bispecifics, and CAR-T therapy, improving outcomes of upfront transplantation is imperative. AFBMTC: Armed Forces Bone Marrow Transplant Centre, CART: chimeric antigen receptor T-cell, CD: cluster of differentiation, CI: confidence interval, CR: complete response, CTD: cyclophosphamide, thalidomide, dexamethasone, CyBorD: cyclophosphamide, bortezomib, dexamethasone, IMiD: immunomodulatory drug, IQR: interquartile range, ISS: International Staging System, MM: multiple myeloma, MPT: melphalan, prednisone, thalidomide, OS: overall survival, PFS: progression-free survival, PR: partial response, R-ISS:..."

Clinical • Real-world • Real-world evidence • Hematological Malignancies • Multiple Myeloma • Oncology

ISATUXIMAB, LENALIDOMIDE, BORTEZOMIB AND DEXAMETHASONE FOR NEWLY-DIAGNOSED, TRANSPLANT-ELIGIBLE MULTIPLE MYELOMA: POST TRANSPLANTATION INTERIM ANALYSIS OF THE RANDOMIZED PHASE III GMMG-HD7 TRIAL (EHA 2024) - "After induction therapy, pts underwent cyclophosphamide-based stem cellcollection and subsequently proceeded to HDT with melphalan (200mg/m2) and ASCT. The present interim analysis of the GMMG-HD7 trial demonstrates that the addition of isatuximab to standard-of-care induction followed by HDT and ASCT results in a significantly higher rate of deep responses and MRDnegativity rates in every treatment phase. The trial is ongoing and evaluates the addition of Isa to lenalidomidemaintenance treatment following second randomization. Figure"

Clinical • P3 data • P3 data: top line • Post-transplantation • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Isolated and Dynamic Peripheral Blood Residual Disease Status Characterized By Mass Spectrometry Predicts Outcome in Patients with High Risk Smoldering Multiple Myeloma Treated in the GEM-CESAR Trial (ASH 2023) - " Pts received induction with six 4-week cycles of KRd (K: 36mg/m2 twice weekly, R: lenalidomide 25mg po od days 1-21 and d: dexamethasone 40mg po weekly), high-dose melphalan followed by ASCT, consolidation with two further cycles of KRd and up to 2 years of maintenance with Rd (R: 10mg po od, d: 20mg po weekly). In this cohort of high-risk smoldering MM patients treated intensively with a curative intention, whereas standard CR or better was not associated with clinical outcome, PRD status defined by mass-spectrometry segregated two groups of patients with different PFS at the 2 time points analyzed. Furthermore, this outcome was better predicted when PRD dynamics were analyzed and/or with the evaluation of severe IMI on PRD+ patients, highlighting once again the relevance of immune recovery as a determinant factor in the evolution of the disease."

Biomarker • Clinical • Residual disease • Hematological Malignancies • Multiple Myeloma • Oncology • Smoldering Multiple Myeloma

Clinical Implications of Discordant Frailty Assessment in Non-Transplant Eligible Patients with Newly Diagnosed Multiple Myeloma: Results from the Randomized Phase IV REAL MM Trial (IMS 2026) - P4 | " REAL MM is a randomized, multicenter, phase IV trial (NCT03829371, funded by the Italian Medicines Agency AIFA - Independent Research) comparing bortezomib-melphalan-prednisone ( VMP) +/- daratumumab (DVMP) vs. lenalidomide-dexamethasone (Rd) +/- daratumumab (DRd) in real-life NTE NDMM pts. Our analysis showed that pts classified as frail by Simplified-FS but fit/intermediate-fit by IMWG-FSs had better clinical outcomes than those frail by both FS and similar outcomes to those fit/intermediate-fit by both FSs. The Simplified-FS may overestimate frailty, whereas the IMWG-FS may better capture frailty status. Currently, according to the latest guidelines suggesting a frailty-adapted approach (quadruplet for non-frail and triplets for frail pts), IMWG-FS remains the gold standard for pt stratification to avoid undertreatment."

Clinical • Discordant • P4 data • Geriatric Disorders • Hematological Malignancies • Multiple Myeloma • Transplantation

Carfilzomib induction, consolidation, and maintenance with or without autologous stem-cell transplantation in patients with newly diagnosed multiple myeloma: pre-planned cytogenetic subgroup analysis of the randomised, phase 2 FORTE trial. (PubMed, Lancet Oncol) - P2 | "This preplanned analysis of the FORTE trial showed that carfilzomib-based induction-intensification-consolidation regimens are effective strategies in patients with standard risk (zero HRCA) and high-risk (one HRCA) myeloma, resulting in similar rates of progression-free survival and 1-year sustained minimal residual disease negativity. Despite promising progression-free survival, patients with ultra-high-risk disease (those with 2 or more HRCA) still have an increased risk of progression and death and therefore represent an unmet medical need."

Journal • P2 data • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation • SDC1

Long-Term Outcome of a Prospective Randomized Trial Comparing Continuous Lenalidomide/Dexamethasone with Lenalidomide/Dexamethasone Induction, MEL140 with Autologous Blood Stem Cell Transplantation and Single Agent Lenalidomide Maintenance in Patients of Age 60-75 Years with Newly Diagnosed Multiple Myeloma (ASH 2022) - P3 | "The addition of daratumumab to this therapy is the best treatment option today for patients who are not transplant eligible. Intensity-reduced high-dose melphalan (MEL140) with autologous transplantation also is an effective treatment option for older patients who are transplant eligible but may not tolerate full dose high-dose melphalan (MEL200)... In the intention-to-treat population, the combination of MEL140 with lenalidomide/dexamethasone induction and lenalidomide single agent maintenance was not superior to continuous lenalidomide/dexamethasone treatment. Subgroup analyses with a focus on the role of transplant will be presented at the meeting. Sponsor: Gesellschaft für Medizinische Innovation in der Hämatologie/Onkologie – GMIHO"

Clinical • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Multiple Sclerosis • Oncology • Solid Tumor • Transplantation

Ixazomib Plus Lenalidomide/Dexamethasone (IRd) Versus Lenalidomide /Dexamethasone (Rd) Maintenance after Autologous Stem Cell Transplant in Patients with Newly Diagnosed Multiple Myeloma: Results of the Spanish GEM2014MAIN Trial (ASH 2021) - "Background: The Spanish Myeloma Group (GEM) demonstrated that post-transplant maintenance with thalidomide plus bortezomib was superior to thalidomide alone, although this combination was associated with a high rate of peripheral neuropathy...Patients : Patients who where at least with stable disease after the GEM2012menos65 trial that included VRD-GEM induction, autologous hematopoietic stem cell transplantation conditioned with either melphalan-200 or intravenous busulfan together with melphalan-140 and consolidation with VRD-GEM were randomized to receive maintenance treatment with IRd versus Rd... After a median follow-up of 56 months, there was no difference in PFS between the two maintenance arms (median not reached, PFS at 5 years: 62% vs. 63% with IRd and Rd, respectively, p=0.785) (figure 1). In the overall series, there were no significant differences in PFS or OS among patients with standard (SR) or high-risk (HR) cytogenetics."

Clinical • Bone Marrow Transplantation • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Neutropenia • Oncology • Pain • Plasmacytoma • Thrombocytopenia • Transplantation

Improving Real-World Outcomes in the Frail and Elderly with Myeloma: Data from the UK Haematological Malignancy Research Network (IMS 2026) - "Shifting trends in treatment options for the ≥ 80s can be seen, with oral melphalan and CTDa dominating in 2005-2010, transient use of RCD during the UKMRA Myeloma XI trial, bortezomib - based combinations gaining popularity from 2014 , followed by IRD in the UKMRA FiTNEss study from 2020. It is encouraging that real-world OS is now improving in those aged ≥ 80. T his likely reflects not only access to novel agents, but a better understanding of how to employ them optimally to balance toxicity and efficacy in frailer patients ( e.g once - vs twice - weekly bortezomib , pre-emptive IMiD dose reductions and rapid steroid tapering etc.) . F urther improvements are anticipated following daratumumab adoption ."

Clinical • Real-world • Real-world evidence • Geriatric Disorders • Hematological Malignancies • Multiple Myeloma • Oncology

Concurrent Chronic Active Epstein-Barr Virus Disease and Extranodal NK/T-Cell Lymphoma as an Isolated Orbital Recurrence After Autologous Stem Cell Transplantation: A Case Report (SOHO 2026) - "She received reduced-dose dexamethasone, cisplatin, gemcitabine, pegaspargase (DDGP) with partial metabolic response after 3 cycles. Our case demonstrates that CAEBV-associated clonal T-cell disease and ENKTL can coexist in the same anatomic site, highlighting the importance of integrated clinical, morphologic, immunophenotypic, and molecular evaluation. ASCT: autologous stem cell transplantation; BEAM: carmustine, etoposide, cytarabine, and melphalan; CD: cluster of differentiation; CHOP: cyclophosphamide, doxorubicin, vincristine, and prednisone; DDX3X: DEAD-box helicase 3 Xlinked; EBER: EBV-encoded small RNA; EBV: Epstein-Barr virus; KMT2D: lysine methyltransferase 2D; MRI: magnetic resonance imaging; NK: natural killer; PCR: polymerase chain reaction; TCR: T-cell receptor; TIA-1: T-cell intracellular antigen-1."

Case report • Clinical • IO biomarker • Extranodal Natural Killer/T-cell Lymphoma • Hematological Malignancies • Lymphoma • Natural Killer/T-cell Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • CD2 • CD4 • CD5 • CD7 • CD8 • DDX3X • KMT2D • NCAM1

Curative Strategy for High-Risk Smoldering Myeloma: Carfilzomib, Lenalidomide, and Dexamethasone (KRd) Followed by Transplant, KRd Consolidation, and Rd Maintenance. (PubMed, J Clin Oncol) - "Although a longer follow-up is needed, this curative approach is encouraging and more effective than active MM, with 31% of the patients maintaining the uMRD 4 years after HDM-ASCT."

Journal • Bone Marrow Transplantation • Endocrine Disorders • Hematological Disorders • Hematological Malignancies • Infectious Disease • Metabolic Disorders • Multiple Myeloma • Neutropenia • Oncology • Orthopedics • Renal Disease • Transplantation

A Collagen-Hydroxyapatite 3D Bone Marrow Model Recapitulates Microenvironment-Mediated Drug Resistance in Multiple Myeloma (IMS 2026) - "Specifically, in NCI-H929 cells, IC 50 increased from 1.86 nM to 3.51 nM for bortezomib, from 4.98 nM to 19.20 nM for carfilzomib, from 0.06 μM to 24.73 μM for lenalidomide, from 0.30 μM to 0.92 μM for pomalidomide, and from 2.14 μM to 4.90 μM for melphalan. BM3Ds reproduce structural and biomechanical features of the BM niche while supporting stromal, endothelial, and MM cell interactions in a physiologically relevant three-dimensional context. The consistent increase in drug resistance observed across multiple therapeutic classes suggests that BM3Ds capture microenvironment-mediated protection mechanisms not observed in standard 2D cultures. This scalable platform supports primary patient-derived samples and provides a preclinical platform for ex vivo drug testing in MM."

Hematological Malignancies • Multiple Myeloma • ANXA5 • CSF2 • IL10 • IL2 • IL6 • SDC1 • SLAMF7

Induction and extended consolidation with daratumumab, cyclophosphamide, bortezomib, lenalidomide, and dexamethasone in patients with high-risk multiple myeloma (OPTIMUM/MUKnine): 5-year follow-up of a multicentre, externally controlled, phase 2 trial. (PubMed, Lancet Oncol) - P2 | "OPTIMUM shows sustained progression-free survival and overall survival improvement with risk-stratified extended therapy, supporting implementation of molecular diagnostics and tailored treatment in patients with newly diagnosed high-risk multiple myeloma."

Journal • P2 data • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology • Transplantation

Isatuximab, Lenalidomide, Bortezomib and Dexamethasone Induction Therapy for Transplant-Eligible Patients with Newly Diagnosed Multiple Myeloma: Final Progression-Free Survival Analysis of Part 1 of an Open-Label, Multicenter, Randomized, Phase 3 Trial (GMMG-HD7) (ASH 2024) - P3 | "Following induction therapy, pts underwent cyclophosphamide-based stem cell collection and subsequently proceeded to high-dose melphalan (200 mg/m2) and autologous hematopoietic stem cell transplant (ASCT). The present analysis of the GMMG-HD7 trial supports the MRD negativity benefit reported previously. The trial is ongoing and will evaluate the addition of Isa to lenalidomide during maintenance after a re-randomization (part 2)."

Clinical • P3 data • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • Nephrology • Oncology • Renal Disease • Transplantation

Resetting the Aberrant Methylation Landscape and DNA Damage Response in Multiple Myeloma Through MAT2A Targeting Reveals Novel Combination Strategies. (IMS 2026) - " MAT2A knockdown (KD) in OPM2 and AMO-1 cell lines was achieved using doxycycline inducible lentiviral shRNA vectors targeting MAT2A. In conclusion, targeting MAT2A in MM cells reverts aberrant methylation and impairs pro-tumoral signalling offering promising avenues for more effective combination therapies."

Hematological Malignancies • Multiple Myeloma • ANXA5 • KRAS • MAT2A

Lenalidomide, bortezomib, and dexamethasone (RVd) ± autologous stem cell transplantation (ASCT) and R maintenance to progression for newly diagnosed multiple myeloma (NDMM): The phase 3 DETERMINATION trial. (ASCO 2022) - P3 | " Pts with NDMM aged 18-65 y were randomly assigned to receive 3 RVd cycles, stem cell mobilization, and then 5 more RVd cycles (Arm A) or IV melphalan 200 mg/m2 + ASCT and 2 RVd cycles (Arm B). RVd ± ASCT and R maintenance to progression resulted in the longest median PFS reported for each approach, and a highly significant 21.4-mo gain in median PFS benefit using RVd + ASCT. No OS advantage has been observed to date."

Clinical • Late-breaking abstract • P3 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

A phase I, randomized, controlled, multicentre trial of isolated hepatic perfusion in combination with ipilimumab and nivolumab in patients with uveal melanoma metastases (the SCANDIUM 2 trial). (ASCO 2023) - P1 | "In patients with metastatic UM, a single treatment with isolated hepatic perfusion (IHP) with high dose melphalan has shown response rates of 40%, while immune checkpoint blockade with ipilimumab (3 mg/kg) in combination with nivolumab (1 mg/kg) every third week (IPI3/NIVO1 q3w) for four cycles followed by nivolumab monotherapy has shown response rates of 11-18%. For previously untreated patients with liver dominant metastatic uveal melanoma, treatment with IHP in combination with IPI3/NIVO1 had a high, yet manageable toxicity profile. The efficacy of this combination treatment is encouraging, however, one cycle of neoadjuvant IPI3/NIVO1 given before IHP did not seem beneficial, neither in regards to safety nor efficacy. Clinical trial information: NCT04463368."

Clinical • Combination therapy • CNS Disorders • Eye Cancer • Immune Modulation • Melanoma • Oncology • Rare Diseases • Solid Tumor • Uveal Melanoma

Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone (Isa-KRd) in Patients with High-Risk Newly Diagnosed Multiple Myeloma: Planned Interim Analysis of the GMMG-Concept Trial (ASH 2022) - P2 | "The phase II CONCEPT trial (NCT03104842) investigates the quadruplet regimen isatuximab plus KRd (Isa-KRd) in HR NDMM in induction and consolidation including high-dose melphalan (HDM) for pts being transplant-eligible (TE). The CONCEPT trial is the first trial investigating Isa-KRd for HR NDMM in TE and TNE patients. Isa-KRd in induction and consolidation leads to high MRD negativity rates after consolidation in this difficult-to-treat population. Toxicity was consistent with expectations and no new safety signals occurred in this IA."

Clinical • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Targeting NFIL3-MYC Axis as a Novel Therapeutic Strategy in High-Risk Relapsed-Refractory Multiple Myeloma (IMS 2026) - "Subsequently, a focused shRNA library targeting selected genes was performed in NOTCH1-overexpressing U266-N1ΔE cells under selective pressure of lenalidomide, melphalan, or bortezomib. In conclusion, we identified upregulation of NFIL3 as a novel mechanism for drug resistance in high-risk relapsed-refractory MM. RA targets the NFIL3-MYC axis and shows potent anti-MM effects, providing a novel therapeutic strategy for multi-refractory disease even after failure of current immunotherapies."

IO biomarker • Hematological Malignancies • Multiple Myeloma • CASP3 • IL3 • MYC • NOTCH1

Bortezomib-Melphalan-Prednisone (VMP) Vs. Lenalidomide-Dexamethasone (Rd) in Transplant-Ineligible Real-Life Multiple Myeloma Patients: Updated Results of the Randomized Phase IV Real MM Trial (ASH 2022) - P4 | "Bortezomib-melphalan-prednisone (VMP) and lenalidomide-dexamethasone (Rd) have represented standards of care for transplant-ineligible (NTE) newly diagnosed multiple myeloma (NDMM) patients (pts) until the recent introduction of daratumumab (Dara) in the frontline setting. Importantly, following a recent amendment, as of July 2022, enrolled pts will be randomized to Dara-VMP vs Dara-Rd. Decision-making and treatment selection will be further supported by a future analysis of this addition of Dara, based on patient and disease characteristics."

Clinical • P4 data • Dermatology • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Oncology • Pain • Thrombocytopenia • Transplantation

GEM2017FIT Trial: Induction Therapy with Bortezomib-Melphalan and Prednisone (VMP) Followed By Lenalidomide and Dexamethasone (Rd) Versus Carfilzomib, Lenalidomide and Dexamethasone (KRd) Plus/Minus Daratumumab (D), 18 Cycles, Followed By Consolidation and Maintenance Therapy with Lenalidomide and Daratumumab: Phase III, Multicenter, Randomized Trial for Elderly Fit Newly Diagnosed Multiple... (ASH 2023) - "The trial met its primary end point and the MRD(-) rates of 69% for KRd and 79% for D-KRd were significantly higher than VMP9-Rd9 (32%). Overall, the VMP-Rd arm had higher rates of neutropenia, while the D-KRd arm had higher rates of infections leading to death. The trial is ongoing to evaluate long term outcomes."

Clinical • P3 data • Cardiovascular • Congestive Heart Failure • Heart Failure • Hematological Disorders • Hematological Malignancies • Hypertension • Infectious Disease • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia