0000000000020232
AUTHOR
Javier De La Rubia
Spanish Society of Hematology and Hemotherapy expert consensus opinion for SARS-CoV-2 vaccination in onco-hematological patients.
Abstract In the midst of the COVID-19 pandemic, different vaccines in front of SARS-CoV-2 have been approved and administered in different vulnerable populations. As patients with cancer were excluded from pivotal trials of vaccination, little is known on their immunogenic response to these vaccines, particularly in patients with severely impaired immune system. In response to that uncertainty, the Spanish Society of Hematology and Hemotherapy launched an initiative aimed to provide recommendations for vaccination of the main hematological conditions. This document is based on the available information on COVID-19 outcomes, prior knowledge on vaccination in hematological patients, recent pu…
Analysis of treatment efficacy in the GEM-CESAR trial for high-risk smoldering multiple myeloma patients: Comparison between the standard and IMWG MRD criteria and QIP-MS including FLC (QIP-FLC-MS)
8512 Background: The GEM-CESAR trial is a potentially curative strategy for high-risk smoldering multiple myeloma (HRsMM) patients (pts) in which the primary endpoint is the achievement of sustained minimal residual disease (MRD) negativity in the bone marrow (BM) by next generation flow (NGF). The value of BM MRD assessment in MM is proven, but alternative, non-invasive methods, accurately reflecting disease burden are needed. Methods: Pts received six 4-week cycles of KRd as induction (K:36mg/m2 twice weekly, R: lenalidomide 25mg po od days 1-21 and d:dexamethasone 40mg po weekly) followed by melphalan 200mg/m2, two further cycles of KRd as consolidation and up to 2 years of Rd (R:10mg/d…
Qip-Mass Spectrometry in High Risk Smoldering Multiple Myeloma Patients Included in the GEM-CESAR Trial: Comparison with Conventional and Minimal Residual Disease IMWG Response Assessment
Introduction: The GEM-CESAR trial is a potentially curative strategy for high-risk smoldering multiple myeloma (HRsMM) patients in which the primary endpoint is the assessment of bone marrow minimal residual disease negativity by next generation flow (NGF). However, alternative methods of tumor burden evaluation in serum, like Quantitative Immunoprecipitation Mass Spectrometry (QIP-MS), a polyclonal antibody-based technology to identify intact immunoglobulins, have been also evaluated. Patients and Methods: Ninety HRsMM patients included in the GEM-CESAR trial received six 4-weeks cycles of carfilzomib, lenalidomide and dexamethasone followed by high dose melphalan and ASCT and 2 further cy…
Single-Cell Characterization of the Multiple Myeloma (MM) Immune Microenvironment Identifies CD27-Negative T Cells As Potential Source of Tumor-Reactive Lymphocytes
Background: The broad use of immunomodulatory drugs (IMiDs) and the breakthrough of novel immunotherapies in MM, urge the optimization of immune monitoring to help tailoring treatment based on better prediction of patients' response according to their immune status. For example, current T cells immune monitoring is of limited value because the phenotype of tumor-reactive T cells is uncertain. Aims: To characterize the MM immune microenvironment at the single-cell level and to identify clinically relevant subsets for effective immune monitoring. Methods: We used a semi-automated pipeline to unveil full cellular diversity based on unbiased clustering, in a large flow cytometry dataset of 86 n…
Caplacizumab prevents refractoriness and mortality in acquired thrombotic thrombocytopenic purpura: integrated analysis
Abstract The efficacy and safety of caplacizumab in individuals with acquired thrombotic thrombocytopenic purpura (aTTP) have been established in the phase 2 TITAN and phase 3 HERCULES trials. Integrated analysis of data from both trials was conducted to increase statistical power for assessing treatment differences in efficacy and safety outcomes. Caplacizumab was associated with a significant reduction in the number of deaths (0 vs 4; P < .05) and a significantly lower incidence of refractory TTP (0 vs 8; P < .05) vs placebo during the treatment period. Consistent with the individual trials, treatment with caplacizumab resulted in a faster time to platelet count response (ha…
T(11;14) and High BCL2 Expression Are Predictive Biomarkers of Response to Venetoclax in Combination with Bortezomib and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma: Biomarker Analyses from the Phase 3 Bellini Study
Background: Overexpression of the anti-apoptotic BCL-2 protein promotes multiple myeloma (MM) cell survival. Venetoclax (Ven) is a highly selective, potent, oral BCL-2 inhibitor that induces apoptosis and has shown synergistic activity with bortezomib (B) and dexamethasone (d). Phase 1 studies in relapsed/refractory (RR) MM demonstrated encouraging clinical efficacy of Ven + d in t(11;14) MM and in a broader patient (pt) population in combination with Bd. Recent results from the Phase 3 BELLINI study of Ven vs placebo (Pbo) + Bd in pts with RRMM demonstrated that pts treated with Ven + Bd had improved clinical response rates and progression-free survival (PFS) vs Pbo, although the overall s…
Efficacy of Caplacizumab in Patients with aTTP in the HERCULES Study According to Baseline Disease Severity
Background: Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare, life-threatening autoimmune thrombotic microangiopathy that involves abnormal processing of von-Willebrand factor (vWF) and results in multiple organ dysfunction. Although aTTP remains a very unpredictable disease, risk factors for death include older age, lactate dehydrogenase (LDH) levels >10x the upper limit of normal (ULN), and cerebral involvement (i.e., the French severity score) (Benhamou et al. Haematologica 2012;97:1181-1186). In addition, raised cardiac troponin-I (cTnI) levels of >2.5 µg/L have also been linked with a higher risk of mortality or refractoriness (Benhamou et al. J Thromb Haemost 2015;1…
CYP2C8 gene polymorphism and bisphosphonate-related osteonecrosis of the jaw in patients with multiple myeloma
Osteonecrosis of the jaw is an uncommon but potentially serious complication of bisphosphonate therapy in multiple myeloma. Previous studies showed that the presence of one or two minor alleles of the cytochrome P450, subfamily 2C polypeptide 8 gene (CYP2C8) polymorphism rs1934951 was an independent prognostic marker associated with development of osteonecrosis of the jaw in multiple myeloma patients treated with bisphosphonates. The aim of this study was to validate the frequency of SNP rs193451 in 79 patients with multiple myeloma. In 9 (22%) patients developing osteonecrosis of the jaw, a heterozygous genotype was found, in contrast with those who did not develop osteonecrosis of the jaw…
Tumor lysis syndrome in patients with acute myeloid leukemia: identification of risk factors and development of a predictive model
Background Despite the prophylactic use of allopurinol, tumor lysis syndrome (TLS)- related morbidity and mortality still occur in a number of patients with acute myeloid leukemia (AML).The aim of this study was: (i) to analyze the incidence and outcome of TLS in a large series of patients with AML receiving hyperhydration and allopurinol, (ii) to identify risk factors for TLS, and (iii) to develop a prognostic scoring system for estimating individual risk of TLS. Design and Methods The study included 772 adult patients with AML receiving induction chemotherapy between 1980 and 2002. TLS was divided into laboratory TLS (LTLS) or clinical TLS (CTLS).The population study was randomly divided …
Randomized Trial of Lenalidomide and Dexamethasone Versus Clarythromycin, Lenalidomide and Dexamethasone As First Line Treatment in Patients with Multiple Myeloma Not Candidates for Autologous Stem Cell Transplantation: Results of the GEM-Claridex Clinical Trial
Continuous treatment with lenalidomide (R) and dexamethasone (d) is a standard of care for multiple myeloma (MM) patients (pts) not candidates for autologous stem cell transplantation (ASCT). As previously reported, the addition of Clarithromycin (C) to Rd has proven to be safe and effective, and case-control analyses suggested a significant additive value with the combination. C optimizes the therapeutic effect of glucocorticoids by increasing the area under the curve, has immunomodulatory effects and may have direct antineoplastic properties. However, there are not randomized phase III trials confirming these results. GEM-Claridex in an open, randomized, phase III trial for untreated new…
Efficacy and safety of open-label caplacizumab in patients with exacerbations of acquired thrombotic thrombocytopenic purpura in the HERCULES study.
BACKGROUND Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare, life-threatening autoimmune thrombotic microangiopathy. Caplacizumab, an anti-von Willebrand Factor Nanobody® , is effective for treating aTTP episodes and is well tolerated. OBJECTIVES AND METHODS In the phase 3 HERCULES trial (NCT02553317), patients with aTTP received double-blind caplacizumab or placebo during daily therapeutic plasma exchange (TPE) and for ≥30 days thereafter. Patients who experienced an exacerbation while on blinded study drug treatment switched to receive open-label caplacizumab plus re-initiation of daily TPE. Exacerbations were defined as recurrence of disease occurring within 30 days after ce…
Measurable Residual Disease by Next-Generation Flow Cytometry in Multiple Myeloma.
[Purpose] Assessing measurable residual disease (MRD) has become standard with many tumors, but the clinical meaning of MRD in multiple myeloma (MM) remains uncertain, particularly when assessed by next-generation flow (NGF) cytometry. Thus, we aimed to determine the applicability and sensitivity of the flow MRD-negative criterion defined by the International Myeloma Working Group (IMWG).
Narratives of Patients with Fatal Outcomes During the Phase 2 TITAN and Phase 3 HERCULES Studies
Background: Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare but life-threatening thrombotic microangiopathy, with an untreated mortality rate of >90%. Prompt treatment with therapeutic plasma exchange (TPE) and immunosuppression improves outcomes in patients with aTTP, but 10-20% of patients still die acutely from this disease. The aim of this analysis was to describe in more detail the characteristics and disease courses of the patients who died during the caplacizumab clinical development program. Methods: Patient narratives on all deaths occurring during the phase 2 TITAN and phase 3 HERCULES studies were extracted. Results: In the overall study periods, a total of 6 pat…
Final Overall Survival Results from BELLINI, a Phase 3 Study of Venetoclax or Placebo in Combination with Bortezomib and Dexamethasone in Relapsed/Refractory Multiple Myeloma
Abstract Background: Multiple myeloma (MM) is a heterogenous cancer of terminally differentiated plasma cells that typically express elevated levels of antiapoptotic proteins, such as BCL-2. Venetoclax (Ven), a highly selective, potent, oral BCL-2 inhibitor, induces apoptosis in MM cells, and when combined with bortezomib and dexamethasone showed promising efficacy in patients (pts) with relapsed/refractory MM (RRMM; Moreau et al. Blood. 2017;130:2392-2400). The Phase 3 BELLINI study primary analysis showed significantly improved response rates and progression-free survival (PFS) in pts with RRMM treated with Ven added to bortezomib and dexamethasone versus placebo (Pbo); however, increased…
Factors Associated with Mortality in Patients Experiencing First Episodes of Acquired Thrombotic Thrombocytopenic Purpura (aTTP). Results of the Spanish TTP Registry
Introduction: Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare, but life-threatening, hematological disorder characterized by severe thrombocytopenia, hemolytic microangiopathic anemia, and frequent organ damage. The underlying pathophysiology of aTTP is a functional deficiency of plasma ADAMTS13 activity caused by antibodies directed against the ADAMTS13 protease. Despite plasma exchange (PEX) and immunosuppression with corticosteroids, and, more recently, rituximab, which achieve remission in most patients with aTTP, 10-20% of patients are refractory to treatment and die as a result of disease progression. Most of such deaths occur during first episodes of aTTP, as subsequent…
Single‐agent daratumumab in patients with relapsed and refractory multiple myeloma requiring dialysis: results of a Spanish retrospective, multicentre study
Correspondence.
INTEGRATED EFFICACY RESULTS FROM THE PHASE 2 AND PHASE 3 STUDIES WITH CAPLACIZUMAB IN PATIENTS WITH ACQUIRED THROMBOTIC THROMBOCYTOPENIC PURPURA
Objective: An integrated analysis based on the Phase 2 TITAN (NCT01151423) and Phase 3 HERCULES (NCT02553317) studies with caplacizumab (CPLZ) in acquired thrombotic thrombocytopenic purpura (aTTP) was performed to assess treatment differences on efficacy and safety outcomes that may have been undetected in the individual trials. Methodology: In both trials, patients with an acute episode of aTTP were randomized to receive CPLZ or placebo (PBO) in addition to therapeutic plasma exchange (TPE) and immunosuppression. All randomized patients from both studies were included in the integrated efficacy analyses (CPLZ: n=108; PBO: n=112), and those who received at least 1 dose of the study drug we…
Redefining outcomes in immune TTP: an international working group consensus report
Abstract Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a potentially fatal thrombotic microangiopathy caused by autoantibody-mediated severe deficiency of ADAMTS13. Standardized definitions of response, exacerbation, remission, and relapse were initially proposed in 2003 and modified by the International Working Group for TTP in 2017. These definitions, which have been widely used in clinical practice and research, are based primarily on the platelet count and are benchmarked against the timing of discontinuation of therapeutic plasma exchange (TPE). They do not incorporate ADAMTS13 activity or the temporizing effects on the platelet count of caplacizumab, a novel anti–von W…
Deep MRD profiling defines outcome and unveils different modes of treatment resistance in standard- and high-risk myeloma
PETHEMA/GEM Cooperative Group.
Incidence, Diagnosis, and Outcome of Acquired Thrombotic Thrombocytopenic Purpura (aTTP): A Nationwide Survey By the Spanish Apheresis Group
Introduction: Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare disease characterized by a severe deficiency of the enzymatic activity of ADAMTS13 caused by autoantibodies, with an incidence of 3-4 x106inhabitants per year according to the few published data available. Accurate estimates of the incidence of aTTP are important to assess the resources required for current treatments and to anticipate the need to develop new treatments. The aim of this study was to determine the actualincidence of aTTP in Spain, as well as its diagnosis, management, and associated complications. Material and methods:A cross-sectional surveywascarried out among hematologists working in Spanish hospi…
Multiple Myeloma Treatment in Real-world Clinical Practice: Results of a Prospective, Multinational, Noninterventional Study.
© 2018 The Authors.
A critical evaluation of caplacizumab for the treatment of acquired thrombotic thrombocytopenic purpura
Introduction: Acquired thrombotic thrombocytopenic purpura (aTTP) is a thrombotic microangiopathy caused by inhibitory autoantibodies against ADAMTS13 protein. Until recently, the combination of plasma exchange (PEX) and immunosuppression has been the standard front-line treatment in this disorder. However, aTTP-related mortality, refractoriness, and relapse are still a matter of concern. Areas covered: The better understanding of the pathophysiological mechanisms of aTTP has allowed substantial improvements in the diagnosis and treatment of this disease. Recently, the novel anti-VWF nanobody caplacizumab has been approved for acute episodes of aTTP. Caplacizumab is capable to block the adh…
Updated Analysis of Bellini, a Phase 3 Study of Venetoclax or Placebo in Combination with Bortezomib and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma
Background: Venetoclax (Ven) is a highly selective, potent, oral BCL-2 inhibitor that induces apoptosis in multiple myeloma (MM) cells and has shown synergistic activity with the proteasome inhibitor (PI) bortezomib (B) and dexamethasone (d). Ven ± d had encouraging clinical efficacy in both t(11;14) MM and in pts irrespective of genetic background when administered with B, with a tolerable safety profile in Phase 1 studies. Here, we provide updated efficacy and safety of Ven vs placebo (Pbo) + Bd in pts with relapsed/refractory (RR) MM, including subgroup analyses, in the BELLINI study. Methods: BELLINI (NCT02755597) was a Phase 3, randomized, double-blind, multicenter study of Ven or Pbo…
Clinical Significance and Biomarkers to Predict Unsustained Complete Remission in Transplant-Eligible Multiple Myeloma
Background: Transplant-eligible MM patients are achieving unprecedented CR rates with frontline therapy. This urges the question about what other tests are informative upon a negative immunofixation (IFx-), as well as if patients with short duration CR continue having dismal survival with modern frontline plus salvage therapies and if so, how to predict risk of unsustained CR. Aim: To provide an optimal definition of unsustained CR and biomarkers to predict it in transplant-eligible MM patients treated with optimal therapy. Methods: A total of 262 patients enrolled in the PETHEMA/GEM2012MENOS65 trial and who were in CR after receiving six induction cycles of bortezomib, lenalidomide and dex…
Longitudinal Immunogenomic Profiling of Tumor and Immune Cells for Minimally-Invasive Monitoring of Smoldering Multiple Myeloma (SMM): The Immunocell Study
Background: Although great strides were made in the management of MM, our best chances to eradicate this malignancy may lie in preventing its progression.Most current models to predict risk of transformation in SMM are commonly established at diagnosis and not reevaluated over time, because some parameters such as tumor burden or genetic abnormalities require invasive bone marrow (BM) aspirates. It could be hypothesized that periodic monitoring of tumor biomarkers is needed to improve risk-stratification of SMM patients, and so would be new minimally-invasive methods that can replace those performed in BM samples. Such methods should also monitor immune profiles, to identify patients with s…
Efficacy of Caplacizumab in Patients with aTTP in the HERCULES Study According to Initial Immunosuppression Regimen
Background: Acquired thrombotic thrombocytopenic purpura (aTTP) is an acute, life-threatening thrombotic microangiopathy that requires urgent and specialized treatment. Prior to the introduction of caplacizumab, the treatment for aTTP was based on daily therapeutic plasma exchange (TPE; to replenish functional ADAMTS13 enzyme) plus immunosuppression (mainly corticosteroids and rituximab; to suppress anti-ADAMTS13 autoantibody production). TPE combined with immunosuppressive therapy improved outcomes in patients; however, episodes of aTTP are still associated with an acute mortality of up to 20% as these therapies do not have an immediate effect on the pathologic microvascular thrombosis. Th…
Long-Term Safety and Efficacy of Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura (aTTP): The Post-HERCULES Study
Abstract Background: The post-HERCULES trial (NCT02878603) evaluated long-term safety and efficacy of caplacizumab in patients with acquired thrombotic thrombocytopenic purpura (aTTP; also known as immune-mediated TTP), and efficacy of repeated use of caplacizumab for aTTP recurrence. Methods: Patients who completed the HERCULES trial were invited to participate in the post-HERCULES study and attend twice-yearly visits for 3 years. In case of aTTP recurrence, patients could receive open-label (OL) caplacizumab with therapeutic plasma exchange (TPE) and immunosuppression (IST). Safety was assessed during the overall study period (intention-to-observe [ITO] population) and during recurrences.…
Post-transplant cyclophosphamide and sirolimus based graft-versus-host disease prophylaxis after allogeneic stem cell transplantation for acute myeloid leukemia.
Post-transplant cyclophosphamide (PTCy) has emerged as a promising graft-versus-host disease (GvHD) prophylaxis in allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, no studies have reported the efficacy of a GvHD prophylaxis based on PTCy with sirolimus (Sir-PTCy) in patients with acute myeloid leukemia (AML). In this retrospective study, we analyze the use of sirolimus in combination with PTCy, with or without mycophenolate mofetil (MMF), on 242 consecutive adult patients with AML undergoing a myeloablative first allo-HSCT from different donor types, in three European centers between January 2017 and December 2020. Seventy-seven (32%) patients received allo-HSCT from…
Severity of Covid-19 Clinical Outcomes and Mortality in Multiple Myeloma Patients over Year 1 of the Pandemic
Abstract Introduction In the first weeks of the Covid-19 pandemic when healthcare systems in many areas were overstretched, we documented that hospital mortality in multiple myeloma (MM) patients infected by Sars-Cov-2 was 50% higher than in age matched Covid-19 patients without cancer. In the following months, the pressure on healthcare systems in Spain continued although it did not reach the extreme levels of the first weeks of the pandemic. In this study, we proposed to determine if the severity of Covid-19 outcomes in MM patients has changed over the first year of the pandemic. Patients and methods The Spanish MM Collaborative Group (Pethema-GEM) conducted a survey at national level on …
Safety of Caplacizumab in Patients Without Documented Severe ADAMTS13 Deficiency During the HERCULES Study
Background: Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare, life-threatening autoimmune thrombotic microangiopathy caused by a deficiency in the activity of ADAMTS13 leading to the formation of ultra-large multimers of von Willebrand factor (vWF) and abnormal platelet adhesion in the microvasculature. aTTP requires prompt diagnosis and rapid initiation of treatment to limit the risk of negative or fatal outcomes. The clinical diagnosis of aTTP is based on thrombocytopenia and microangiopathic hemolytic anemia and is confirmed by ADAMTS13 <10%. However, the latter confirmation is not always rapidly available, and treatment is typically initiated based on the clinical diagno…
Therapeutic plasma exchange: Review of current indications
Therapeutic plasma exchange (TPE) is the extracorporeal technique performed in an apheresis device were patient's plasma is separated from whole blood and removed, while the cellular blood components are returned to the patient together with a replacement fluid. By the extracorporeal removal of pathological substances and the replacement of deficient plasma components, it constitutes an important tool for the management of several disorders and it is a well-known and established treatment for numerous diseases. Additionally, overall available data confirm the safety and efficacy of TPE. Nevertheless, the quality of the evidence supporting the utility and efficacy of the procedure is diverse…
Results of an Early Access Treatment Protocol of Daratumumab Monotherapy in Spanish Patients With Relapsed or Refractory Multiple Myeloma
Daratumumab is a human CD38-targeted monoclonal antibody approved as monotherapy for heavily pretreated relapsed and refractory multiple myeloma. We report findings for the Spanish cohort of an open-label treatment protocol that provided early access to daratumumab monotherapy and collected safety and patient-reported outcomes data for patients with relapsed or refractory multiple myeloma. At 15 centers across Spain, intravenous daratumumab (16 mg/kg) was administered to 73 patients who had >= 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug, or who were double refractory to both. The median duration of daratumumab treatment was 3.3 (range: 0.03-13.17)…
Heavy and Light Chain Monitoring in High Risk Smoldering Multiple Myeloma Patients Included in the GEM-CESAR Trial: Comparison with Conventional and Minimal Residual Disease IMWG Response Assessment
Introduction: The GEM-CESAR trial is a potentially curative strategy for high-risk smoldering multiple myeloma (HRsMM) patients (pts) in which the primary endpoint is the achievement of bone marrow minimal residual disease (MRD) negativity. However, other methods of disease evaluation in serum such as heavy+light chain (HLC) assessment, with a potential complementary value to the IMWG response criteria, have also been tested. Aim: To evaluate the performance of HLC assay in HRsMM pts at diagnosis and after consolidation, comparing the results with standard serological methods and Next Generation Flow (NGF) for the assessment of bone marrow MRD. Patients and Methods: Ninety HRsMM pts include…
Assessment of Treatment Response By Ife, Next Generation Flow Cytometry and Mass Spectrometry Coupled with Liquid Chromatography in the GEM2012MENOS65 Clinical Trial
Abstract Introduction : In patients (pts) with multiple myeloma (MM), next generation flow cytometry (NGF) and next generation sequencing have shown an increased capacity to identify the presence of disease and to anticipate patient's prognosis as compared to serum protein immunofixation (IFE). However, both methods rely on bone marrow (BM) samples and it is important to explore alternative techniques applicable in more accessible samples such as peripheral blood. Patients and Methods: Newly diagnosed MM pts enrolled in the PETHEMA/GEM2012MENOS65 trial received six cycles of induction with bortezomib, lenalidomide and dexamethasone (VRD), intensification with high-dose therapy (melphalan or…
Circulating tumor and immune cells for minimally invasive risk stratification of smoldering multiple myeloma
Abstract Purpose: Early intervention in smoldering multiple myeloma (SMM) requires optimal risk stratification to avoid under- and overtreatment. We hypothesized that replacing bone marrow (BM) plasma cells (PC) for circulating tumor cells (CTC), and adding immune biomarkers in peripheral blood (PB) for the identification of patients at risk of progression due to lost immune surveillance, could improve the International Myeloma Working Group 20/2/20 model. Experimental Design: We report the outcomes of 150 patients with SMM enrolled in the iMMunocell study, in which serial assessment of tumor and immune cells in PB was performed every 6 months for a period of 3 years since enrollment. Resul…
Venetoclax or placebo in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (BELLINI): a randomised, double-blind, multicentre, phase 3 trial
Background Venetoclax is a highly selective, potent, oral BCL-2 inhibitor, which induces apoptosis in multiple myeloma cells. Venetoclax plus bortezomib and dexamethasone has shown encouraging clinical efficacy with acceptable safety and tolerability in a phase 1 trial. The aim of this study was to evaluate venetoclax plus bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma. Methods In this randomised, double-blind, multicentre, phase 3 trial, patients aged 18 years or older with relapsed or refractory multiple myeloma, an Eastern Cooperative Oncology Group performance status of 2 or less, who had received one to three previous therapies were enrolled from …
Updated results from BELLINI, a phase III study of venetoclax or placebo in combination with bortezomib and dexamethasone in relapsed/refractory multiple myeloma.
8509 Background: Venetoclax (Ven) is a selective, potent, oral BCL-2 inhibitor. In the Phase 3 BELLINI trial, addition of Ven to bortezomib (B) + dexamethasone (d) significantly improved response rates and progression-free survival (PFS) vs placebo (Pbo) and showed significant efficacy in patients (pts) with either t(11;14) or BCL2high gene expression. Here we present updated safety and efficacy data from the prespecified second interim overall survival (OS) analysis. Methods: In this multicenter, randomized, double-blind study (NCT02755597), pts with relapsed/refractory multiple myeloma (RRMM) with 1-3 prior lines of therapy were randomized 2:1 to Ven (800 mg) or Pbo in combination with B…
Recent Advances in the Treatment of Patients with Multiple Myeloma
Simple Summary The evolving data from trials assessing novel combinations as a part of the frontline and relapse treatment in transplant and non-transplant candidates have markedly improved the anti-myeloma efficacy of the different therapeutic regimens and improved patients’ prognosis. Current treatment objectives are focused to further improve the rate of complete remission, time to progression, progression-free survival and overall survival without increasing toxicity. Besides, different strategies are being developed in the elderly population as this group of patients requires a closer monitoring with individualized, dose-modified regimens to improve tolerability while maintaining their…
Treatment of multiple myeloma-related bone disease
In this Policy Review, the Bone Working Group of the International Myeloma Working Group updates its clinical practice recommendations for the management of multiple myeloma-related bone disease. After assessing the available literature and grading recommendations using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) method, experts from the working group recommend zoledronic acid as the preferred bone-targeted agent for patients with newly diagnosed multiple myeloma, with or without multiple myeloma-related bone disease. Once patients achieve a very good partial response or better, after receiving monthly zoledronic acid for at least 12 months, the treating…
Adoptive transfer of ex vivo expanded SARS‐CoV‐2‐specific cytotoxic lymphocytes: A viable strategy for COVID‐19 immunosuppressed patients?
Cellular and humoral response to acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infections is on focus of research. We evaluate herein the feasibility of expanding virus‐specific T cells (VST) against SARS‐CoV‐2 ex vivo through a standard protocol proven effective for other viruses. The experiment was performed in three different donors' scenarios: (a) SARS‐CoV‐2 asymptomatic infection/negative serology, (b) SARS‐CoV‐2 symptomatic infection/positive serology, and (c) no history of SARS‐CoV‐2 infection/negative serology. We were able to obtain an expanded VST product from donors 1 and 2 (1.6x and 1.8x increase of baseline VST count, respectively) consisting in CD3 + cells (80.3% and 6…
Pomalidomide plus low-dose dexamethasone in patients with relapsed/refractory multiple myeloma and renal impairment: Results from a phase ii trial
Purpose Renal impairment (RI) limits treatment options in patients with relapsed/refractory multiple myeloma (RRMM). Here, we prospectively studied pomalidomide plus low-dose dexamethasone (LoDEX) in patients with RRMM and moderate or severe RI, including those receiving hemodialysis. Patients and Methods MM-013, a noncomparative, European phase II trial, enrolled three patient cohorts: moderate RI (cohort A; estimated glomerular filtration rate, 30 to < 45 mL/min/1.73 m2); severe RI (cohort B; estimated glomerular filtration rate, < 30 mL/min/1.73 m2); and severe RI that requires hemodialysis (cohort C). Patients received pomalidomide 4 mg/d on days 1 to 21 and LoDEX 20 or 40 mg once…