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Publications (148)
Background: In DREAMM-7 (NCT04246047), belantamab mafodotin (belamaf) plus bortezomib and dexamethasone (BVd) demonstrated a statistically significant and clinically meaningful progression-free survival (PFS) benefit vs the standard-of-care triplet daratumumab, bortezomib, and dexamethasone (DVd) in patients with relapsed or refractory multiple mye...
Background
Use of triplet/quadruplet therapies for 1L multiple myeloma (MM) raises the need for novel combinations at first relapse. In the phase 3 DREAMM-8 (NCT04484623) study, belantamab mafodotin (belamaf) + pomalidomide + dexamethasone (BPd) led to significantly longer progression-free survival (PFS) in the intention-to-treat population than po...
Introduction. Multiple myeloma (MM) is an incurable hematologic malignancy typically affecting older adults. Adding isatuximab (Isa) to bortezomib, lenalidomide and dexamethasone (Isa-VRd) significantly reduced risk of progression or death by 40.4% vs. VRd while providing deep and sustained responses in patients with NDMM who are ineligible for tra...
Patients with multiple myeloma (MM) are initially treated with triplet or quadruplet combination regimens that include proteasome inhibitors, immunomodulators, and anti-CD38 monoclonal antibodies. However, most patients with MM experience progression after initial treatment and need efficacious subsequent-line combinations that incorporate new drug...
Introduction:
In the global Phase 3 IMROZ study (NCT03319667), transplant-ineligible patients (pts) with NDMM demonstrated significantly improved progression-free survival (PFS) with Isa-VRd followed by Isa-Rd compared with VRd followed by Rd, along with deep and sustained responses. Pts in the Isa-VRd arm demonstrated a significantly higher overal...
Background: Daratumumab (Dara) is the first monoclonal antibody introduced into clinical practice to treat multiple myeloma (MM). It currently forms the backbone of therapy regimens in both newly diagnosed (ND) and relapsed/refractory (RR) patients. However, previous reports indicated an increased risk of infectious complications (ICs) during Dara-...
Introduction:
Chronic lymphocytic leukemia (CLL) is one of the most common types of leukemia in adult patients. The landscape of CLL therapy has changed in the last decades with the introduction of antibody-based therapies and novel targeted agents resulting in improved outcomes.
Areas covered:
This article describes the use of monoclonal antibo...
Introduction:
In the last decade, BTK inhibitors and the BCL-2 inhibitor venetoclax have replaced immunochemotherapy in the treatment of CLL.
Areas covered:
This review describes the use of BTK inhibitors and BCL2 inhibitors in the treatment of naive and relapsed or refractory CLL, with particular attention to the mechanisms of resistance. It al...
LBA105
Background: Use of triplet/quadruplet therapies for 1L MM raises the need for novel combinations at first relapse, which belantamab mafodotin (belamaf) combos may address. In DREAMM-7, BVd led to a significant improvement in progression-free survival (PFS) and a strong trend in improved overall survival (OS) vs daratumumab-Vd in patients (pt...
Background:
Bortezomib, lenalidomide, and dexamethasone (VRd) is a preferred first-line treatment option for patients with newly diagnosed multiple myeloma. Whether the addition of the anti-CD38 monoclonal antibody isatuximab to the VRd regimen would reduce the risk of disease progression or death among patients ineligible to undergo transplantati...
Background:
Triplet or quadruplet therapies incorporating proteasome inhibitors, immunomodulators, and anti-CD38 antibodies have led to prolonged survival among patients with newly diagnosed multiple myeloma; however, most patients have a relapse. Frontline lenalidomide therapy has increased the number of patients with lenalidomide-refractory dise...
Background:
Belantamab mafodotin had single-agent activity in patients with relapsed or refractory multiple myeloma, a finding that supports further evaluation of the agent in combination with standard-care therapies.
Methods:
In this phase 3, open-label, randomized trial, we evaluated belantamab mafodotin, bortezomib, and dexamethasone (BVd), a...
7543
Background: Belantamab mafodotin(belamaf), a first-in-class antibody-drug conjugate targeting B-cell maturation antigen, acts through a multimodal mechanism including direct cell killing and immune-mediated mechanisms. The global, phase 3, open-label, randomized, DREAMM-7 trial (NCT04246047) met its primary endpoint of demonstrating statistica...
7503
Background: Patients (pts) with RRMM and poor prognostic features, such as high-risk cytogenetics or disease refractory to major drug classes, have an unmet need. In DREAMM-7 (NCT04246047), BVd demonstrated a statistically significant and clinically meaningful progression-free survival (PFS) benefit vs standard-of-care (SOC) DVd in pts with RR...
Mass spectrometry (MS) can detect multiple myeloma-derived monoclonal proteins in peripheral blood (PB) with high sensitivity, potentially serving as a PB assay for measurable residual disease (MRD). This study evaluated the significance of PB MS MRD negativity during post-transplant therapy in patients with newly diagnosed multiple myeloma. Serum...
Introduction:
Bruton tyrosine kinase inhibitors (BTKi) have been used for the management of human diseases since the approval of the first-in class agent, ibrutinib, by the Food and Drug Administration in 2013 for the treatment of patients with mantle cell lymphoma (MCL). Ibrutinib is a covalent inhibitor along with second-class BTKis: acalabrutin...
439572
Background: Belamaf, a BCMA-targeted antibody drug conjugate, has previously demonstrated clinical activity and a manageable safety profile, supporting its use in combination with standard-of-care (SoC) therapies in RRMM. DREAMM-7 (NCT04246047) is a global, randomized, open-label, phase III head-to-head trial evaluating the efficacy and safe...
Introduction
The systemic inflammation index (SII) might serve as an indicator of the equilibrium between the inflammatory and immune responses. The aim of the study was to determine the clinical value and prognostic significance of SII in the cohort of multiple myeloma (MM) patients treated with a regimen of pomalidomide and dexamethasone (Pd).
M...
Introduction
The interim results of the ATLAS trial (Dytfeld, Lancet Oncology 2023) suggest a progression-free survival (PFS) benefit for NDMM patients after autologous hematopoietic stem cell transplantation (ASCT) treated with MRD-directed and risk-adapted maintenance using KRd compared to single-agent R. In order to gain a better understanding o...
Background/Introduction: Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate that targets aminopeptidases resulting in rapid release of alkylating agents inside tumor cells. Based on the phase 2 HORIZON study and supported by the phase 3, randomized, controlled OCEAN study, melflufen was approved in Europe for use in patien...
Introduction
Minimal residual disease (MRD) assessment in bone marrow (BM) has emerged as one of the strongest prognostic factors in MM. Mass spectrometry (MS), capable of detecting MM-derived monoclonal proteins in peripheral blood with high sensitivity, has the potential to complement standard methods. While its role in evaluating residual diseas...
Introduction
Results of the unplanned interim analysis of the ATLAS trial (Dytfeld, Lancet Oncology 2023) suggest a progression-free survival benefit of carfilzomib, lenalidomide, and dexamethasone (KRd) post-transplant maintenance over single-agent lenalidomide (R). Use of triplet combination, with frequent hospital visits and repeated intravenous...
Despite advances in multiple myeloma (MM) treatment, drug resistance remains a clinical challenge. We aimed to develop a prognostic model for bortezomib resistance based on miRNA expression profiling. The study included 40 previously untreated MM patients receiving bortezomib-based regimens (20 treatment-sensitive, 20 resistant). Pretreatment venou...
Introduction:
Phosphoinositide 3-kinase delta (PI3Kδ) inhibitors are a class of novel agents that are mainly used to treat B-cell malignancies. They function by inhibiting one or more enzymes which are part of the PI3K/AKT/mTOR pathway. Idelalisib is a first-in-class PI3Kδ inhibitor effective in patients with B-cell lymphoid malignancies.
Areas c...
Previous studies suggest that postautologous stem cell transplant (ASCT) recovery of polyclonal immunoglobulin from immunoparesis in patients with multiple myeloma is a positive prognostic marker. We performed a longitudinal analysis of polyclonal immunoglobulin concentrations and unique B‐cell sequences in patients enrolled in the phase 3 ATLAS tr...
A diagnosis of typical chronic lymphocytic leukemia (CLL) requires the presence of ≥5000 clonal B-lymphocytes/μL, the coexistence of CD19, CD20, CD5, and CD23, the restriction of light chain immunoglobulin, and the lack of expression of antigens CD22 and CD79b. Atypical CLL (aCLL) can be distinguished from typical CLL morphologically and immunophen...
Background:
There is an increased risk of second primary malignancies (SMPs) in patients with multiple myeloma (MM). This multinational 'real-world' retrospective study analyzed the characteristics and outcomes of MM patients that developed SPMs.
Results:
165 patients were analyzed: 62.4% males; 8.5% with a prior cancer; 113 with solid SPMs, mai...
A diagnosis of typical chronic lymphocytic leukemia (CLL) requires the presence of ≥5000 clonal B-lymphocytes/μL with the coexistence of CD19, CD20, CD5, and CD23 and the restriction of light chain immunoglobulin, and the lack of expression of antigens CD22 and CD79b. Atypical CLL (aCLL) can be distinguished from typical CLL morphologically and imm...
Introduction:
Bruton's tyrosine kinase (BTK) inhibitors have recently been approved for clinical use against several B-cell indolent lymphoid malignancies, both as single agents or in combination. One second-generation BTK inhibitor that is being developed for the treatment of B-cell hematological malignancies, as well as for autoimmune disorders,...
Introduction
Hairy cell leukemia (HCL) is a rare subtype of indolent lymphoid leukemia originating from a mature B lymphocyte. The standard first-line treatment for classic HCL, and HCL variant (HCLv), consists of purine nucleoside analogs (PNA), with or without rituximab. However, almost half of patients relapse and require subsequent therapy.
Ar...
Background:
Lenalidomide is a cornerstone of maintenance therapy in patients with newly diagnosed multiple myeloma after autologous stem-cell transplantation. We aimed to compare the efficacy and safety of maintenance therapy with carfilzomib, lenalidomide, and dexamethasone versus lenalidomide alone in this patient population.
Methods:
This stu...
Cardiac involvement of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is recognized extremely rarely. In addition, most CLL/SLL patients with heart infiltration are asymptomatic. In this review, we present the results of a literature search for English language articles concerning CLL/SLL or Richter transformation with symptomati...
Introduction
In the last few years, BTK inhibitors, PI3K inhibitors and venetoclax have been approved for clinical use against chronic lymphocytic leukemia (CLL), both as single agents, and in combination.
Areas covered
This article summarizes recent achievements in the treatment of patients with CLL, and pays special attention to novel targeted d...
Hairy cell leukemia (HCL) is a rare type of chronic lymphoid leukemia originating from a mature B lymphocyte. A diagnosis of HCL is based on cytology, confirmed by multiparametric flow cytometry (MFC) studies using anti-B-cell monoclonal antibodies, together with a panel of antibodies more specific to HCL, such as CD11c, CD25, CD103 and CD123. Rece...
Lenalidomide-based regimens are effective treatment options for patients with relapsed/refractory multiple myeloma (RRMM). However, they are associated with an increased risk of infectious complications. This study examines the clinical factors influencing the occurrence of infection in MM patients treated with lenalidomide and dexamethasone (Rd)....
Introduction:
Mitogen-activated protein kinase pathway mutations are present in >50% of patients with relapsed/refractory (R/R) multiple myeloma (MM). MEK inhibitors show limited single-agent activity in R/R MM; combination with B-cell lymphoma-2 (BCL-2) and programmed death-ligand 1 inhibition may improve efficacy. This phase Ib/II trial (NCT0331...
Lenalidomide-based regimens are effective treatment options for patients with relapsed/refractory multiple myeloma (RRMM). However, they are associated with an increased risk of infectious complications. This study examines the clinical factors influencing the occurrence of infection in MM patients treated with lenalidomide and dexamethasone (Rd)....
Multiple myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of plasma cells in the bone marrow (BM) microenvironment. Despite the progress made in treatment, some MM patients still die within the first year of diagnosis. Numerous studies investigating microRNA (miRNA) expression patterns suggest they may be good pr...
Treatment following autologous stem cell transplantation (ASCT) for multiple myeloma (MM) remains an area of active investigation. We have shown that extended post-ASCT treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) after KRd induction improved the depth and duration of response (Jasielec et al, Blood 2020), suggesting a benefit...
8001
Background: Treatment following autologous stem cell transplantation (ASCT) for multiple myeloma (MM) remains an area of active investigation. We have shown that extended post-ASCT treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) after KRd induction improved the depth and duration of response (Jasielec et al, Blood 2020), sugg...
Background
Melphalan flufenamide (melflufen), an alkylating peptide-drug conjugate, plus dexamethasone showed clinical activity and manageable safety in the phase 2 HORIZON study. We aimed to determine whether melflufen plus dexamethasone would provide a progression-free survival benefit compared with pomalidomide plus dexamethasone in patients wit...
Multiple myeloma (MM) is characterized by the malignant proliferation of monoclonal plasma cells in the bone marrow with an elevation in monoclonal paraprotein, renal impairment, hypercalcemia, lytic bony lesions, and anemia. Immune cells and associated cytokines play a significant role in MM growth, progression, and dissemination. While some cytok...
Multiple myeloma (MM) is characterized by the malignant proliferation of monoclonal plasma cells in the bone marrow with an elevation in monoclonal paraprotein, renal impairment, hypercalcemia, lytic bony lesions, and anemia. Immune cells and associated cytokines play a significant role in MM growth, progression, and dissemination. While some cytok...
Multiple myeloma (MM) is a genetically complex disease that results from a multistep transformation of normal to malignant plasma cells in the bone marrow. However, the molecular mechanisms responsible for the initiation and heterogeneous evolution of MM remain largely unknown. A fundamental step needed to understand the oncogenesis of MM and its r...
Background: Older patients (pts) with relapsed/refractory multiple myeloma (RRMM) represent a particularly difficult-to-treat population due to comorbidities, frailty or reduced fitness level, and treatment with concomitant medications (Larocca et al. Leukemia. 2018;32:1697); further, pts may have limited therapeutic options due to ineligibility to...
Background: Most pts with MM will be exposed to alkylators throughout their disease course as part of a multidrug regimen or as high-dose melphalan (HDM) conditioning prior to undergoing an autologous stem cell transplant (SCT). MM invariably relapses and can become refractory to prior treatments. Outcomes are poor for pts with RRMM, highlighting t...
Background: With new standard-of-care and novel treatment options available in MM, outcomes have improved; however, patients (pts) eventually become refractory to multiple drug classes (Gandhi et al. Leukemia. 2019;33:2266). Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate (PDC) that targets aminopeptidases and thereby r...
While multiple myeloma (MM) treatment with proteasome inhibitors and other agents yields encouraging results, primary and secondary resistance remains an emerging problem. An important factor in such treatment resistance is the overexpression of several proteins. The present study comprehensively evaluates the expression of POMP, PSMB5, NRF2, XBP1,...
Multiple myeloma (MM) is a genetically complex disease that results from a multistep transformation of normal to malignant plasma cells in the bone marrow. However, the molecular mechanisms responsible for the initiation and heterogeneous evolution of MM remain largely unknown. A fundamental step needed to understand the oncogenesis of MM and its r...
Background
Proteasome inhibitors (PIs) & monoclonal antibodies are backbones of RRMM treatment; Ixa is approved with lenalidomide-dex for pts with ≥1 prior therapy, & Dara is approved in various regimens, including with bortezomib-dex (DVd). In CASTOR (DVd vs Vd), Vd was limited to 8 cycles; however, prolonged PI therapy is associated with improved...
Objective
We evaluated the efficacy and safety of pomalidomide, bortezomib, and dexamethasone (PVd) vs bortezomib and dexamethasone (Vd) by age, renal function, and high‐risk cytogenetic abnormalities in lenalidomide‐pretreated patients with multiple myeloma at first relapse.
Methods
OPTIMISMM was a phase 3, multicenter, open‐label, randomized stu...
While multiple myeloma (MM) treatment with proteasome inhibitors and other agents yields encouraging results, primary and secondary resistance remains an emerging problem. An important factor in such treatment resistance is the overexpression of several proteins. The present study comprehensively evaluates the expression of POMP, PSMB5, NRF2, XBP1,...
Multiple myeloma (MM) is a common malignant hematological malignancy. Recently, interest has grown in the role of non-coding regions in disease pathogenesis. MicroRNAs (miRNAs) are small non-coding RNAs containing 19-25 bases that play a crucial role in messenger RNA silencing and post-transcriptional regulation of gene expression. Several miRNAs d...
Introduction:
Despite the progress made in multiple myeloma (MM) treatment, approximately 10-15% of patients die within the first year of diagnosis.
Objectives:
To determine early mortality (EM) risk factors in patients with newly diagnosed (ND) MM treated with new drugs in clinical practice.
Patients and methods:
197 patients with symptomatic...
Proteasome inhibitors, like bortezomib, play a key role in the treatment of multiple
myeloma (MM); however, most patients eventually relapse and eventually show multiple drug resistance, and the molecular mechanisms of this resistance remain unclear. The aim of our study is to assess the expression of previously described genes that may influence t...
Proteasome inhibitors, like bortezomib, play a key role in the treatment of multiple myeloma (MM); however, most patients eventually relapse and eventually show multiple drug resistance, and the molecular mechanisms of this resistance remain unclear. The present study examines the expression of previously-described genes that may influence resistan...
Proteasome inhibitors, like bortezomib, play a key role in the treatment of multiple myeloma (MM); however, most patients eventually relapse and eventually show multiple drug resistance, and the molecular mechanisms of this resistance remain unclear. The present study examines the expression of previously-described genes that may influence resistan...
Background
Selinexor combined with dexamethasone has shown activity in patients with heavily pre-treated multiple myeloma. In a phase 1b/2 study, the combination of oral selinexor with bortezomib (a proteasome inhibitor) and dexamethasone induced high response rates with low rates of peripheral neuropathy, the main dose-limiting toxicity of bortezo...
Background
Although the introduction of novel agents improved the survival outcomes in patients with multiple myeloma (MM), some patients died within one year (early mortality, EM) following diagnosis. In this study, we evaluated the EM rate, and investigated the risk factors associated with EM in MM patients.
Aims
In this study we investigated ris...
Introduction: MAPK pathway mutations are present in more than 50% of patients (pts) with relapsed/refractory multiple myeloma (RRMM; Xu et al. Oncogenesis 2017; Kortum et al. Blood 2016). While MEK inhibitors have demonstrated limited single-agent activity in RRMM, combination with BCL-2 inhibition with or without PD-L1 inhibition may improve effic...
Bortezomib is the first-in-class proteasome inhibitor, commonly used in the treatment of multiple myeloma (MM). The mechanisms underlying acquired bortezomib resistance in MM are poorly understood. Several cell-free miRNAs have been found to be aberrantly regulated in MM patients. The aim of this pilot study was to identify a blood-based miRNA sign...
Skeletal involvement is a rare complication of hairy cell leukemia (HCL) with an incidence of approximately 3%. Bone lesions are commonly lytic, and the most common sites of involvement are the femoral head and neck. Skeletal involvement is typically associated with high tumor burden and bone marrow infiltration. However, isolated cases of skeletal...
