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January 2000 - present
January 2000 - present
January 2000 - October 2015
Publications
Publications (294)
Objectives
This final post hoc analysis evaluated patient‐reported outcomes from the Phase 3 MAIA study of daratumumab, lenalidomide, and dexamethasone (D‐Rd) versus lenalidomide and dexamethasone (Rd) after median 64.5‐month follow‐up in transplant‐ineligible patients with newly diagnosed multiple myeloma (NDMM), including patient subgroups.
Meth...
In the MAIA study (median follow-up, 56.2 months), daratumumab plus lenalidomide and dexamethasone (D-Rd) significantly improved progression-free survival (PFS) and overall survival versus lenalidomide and dexamethasone (Rd) alone in transplant-ineligible newly diagnosed multiple myeloma (NDMM). In this post hoc analysis of clinically important sub...
Introduction: Multiple myeloma (MM) remains an incurable disease despite the introduction of several agents in the last two decades. While the standard-of-care (SOC) drugs like proteasome inhibitors (PI), and immunomodulatory drugs (IMiD) are effective in controlling the disease and achieving remissions, disease progression and relapse invariably o...
Introduction
Multiple myeloma (MM) is a hematological malignancy of bone marrow plasma cells. Clinically, it is manifested with a spectrum of symptoms including focal/bone lesions, hypercalcemia, anemia, and renal dysfunction. Bone disease (BD) in MM is characterized by osteopenia, osteoporosis, and osteolytic lesions, significantly impacting quali...
Introduction:
Multiple myeloma (MM) is a hematological malignancy of bone marrow plasma cells, with patient overall survival (OS) ranging from few weeks to more than 10 years. Stratifying at-risk newly diagnosed (NDMM) patients is crucial for tailoring treatment strategies. Historically, prognostic factors such as albumin, lactate dehydrogenase (LD...
Background
Multiple myeloma (MM), an incurable disease characterized by frequent relapses and a need for multiple treatments, often progresses to a relapse/refractory status resistant to all available drugs and drug classes. Bispecific antibodies, specifically BCMA T‐cell engagers, have emerged as effective treatments for MM, demonstrating impressi...
Simple Summary
Outcomes for high-risk myeloma patients are still poor, despite many advances in treatment. In addition, scarce data exist on double maintenance in transplant-eligible high-risk newly diagnosed multiple myeloma (NDMM) patients. We present the results of a prospective study on 120 transplant-eligible NDMM patients with prolonged cytog...
Multiple myeloma (MM) patients have highly variable overallsurvival (OS) ranging from few weeks to more than ten years. Discovering an early biosignature to stratify short-term from long-term survivors offers the prospect of treating at-risk patients. Machine learning (ML) algorithms are currently being tested to discover biosignatures, but they co...
Background
The presence of minimal residual disease (MRD+) following autologous stem cell transplantation (ASCT) in multiple myeloma represents a poor prognostic factor for progression‐free survival (PFS) and overall survival (OS).
Methods
At our department, we recommend lenalidomide maintenance for patients who are MRD+ after ASCT, while MRD‐nega...
8034
Background: Teclistamab is the first B-cell maturation antigen (BCMA) bispecific antibody approved for the treatment of relapsed/refractory multiple myeloma (RRMM) at a dose of 1.5 mg/kg weekly (QW) given subcutaneously. A less frequent dosing schedule offers added convenience and flexibility to patients, physicians, and caregivers. We evaluat...
What is this summary about?:
This is a summary of a clinical trial called MAIA. The trial tested 2 combinations of cancer drugs (daratumumab plus lenalidomide and dexamethasone compared with lenalidomide and dexamethasone) in people with newly diagnosed multiple myeloma. None of the participants who took part in the study had been treated before o...
What is this summary about?:
This is a summary of a phase 1-2 clinical trial called MajesTEC-1. This trial tested the cancer drug teclistamab in people with relapsed or refractory multiple myeloma, a cancer that forms in a certain type of white blood cells known as plasma cells. Most participants who took part in the study had at least 3 prior tre...
PURPOSE
With the initial analysis of POLLUX at a median follow-up of 13.5 months, daratumumab in combination with lenalidomide and dexamethasone (D-Rd) significantly prolonged progression-free survival versus lenalidomide and dexamethasone (Rd) alone in patients with relapsed or refractory multiple myeloma (RRMM). We report updated efficacy and saf...
Multiple myeloma (MM) is an incurable hematological cancer, in which immune checkpoint inhibition (ICI) with monoclonal antibodies (mAbs) has failed due to uncontrollable immune responses in combination therapies and lack of efficacy in monotherapies. Although NK cell-specific checkpoint targets such as NKG2A and KIRs are currently being evaluated...
Objectives
Despite the effectiveness of newer drugs for the treatment of multiple myeloma (MM), the outcomes are further improved by subsequent autologous stem cell transplantation (ASCT). Data on effectiveness in older patients are limited. We compared outcomes in patients aged 65–75 years depending on whether they were treated with ASCT or not an...
Multiple myeloma (MM) is a hematological malignancy characterized by a high risk for thrombotic episodes, mainly venous thromboembolism (VTE). This risk is accentuated by cancer treatments such as immunomodulatory drugs (IMiDs). Cancer-associated thrombosis is one of the leading causes of mortality and morbidity, and the prevention of thrombosis is...
Background:
Teclistamab is a T-cell-redirecting bispecific antibody that targets both CD3 expressed on the surface of T cells and B-cell maturation antigen expressed on the surface of myeloma cells. In the phase 1 dose-defining portion of the study, teclistamab showed promising efficacy in patients with relapsed or refractory multiple myeloma.
Me...
In the phase 3 MAIA study of patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM), daratumumab plus lenalidomide/dexamethasone (D-Rd) improved progression-free survival (PFS) versus lenalidomide/dexamethasone (Rd). We present a subgroup analysis of MAIA by frailty status. Frailty assessment was performed retrospectively using...
In the primary analysis of the phase 3 COLUMBA study, daratumumab by subcutaneous administration (DARA SC) demonstrated non-inferiority to intravenous administration (DARA IV) for relapsed or refractory multiple myeloma (RRMM). Here, we report the final analysis of efficacy and safety from COLUMBA after a median of 29.3 months follow-up (additional...
Background
We wanted to evaluate if health care for multiple myeloma (MM) patients is equal in different regions of Sweden.
Aim
To study differences in survival for MM depending on health care region and early use of modern treatment.
Methods and results
Data from the Swedish Myeloma Register from patients diagnosed between 2008 and 2017 was used...
Background
: The use of reduced intensity conditioning (RIC) regimens has decreased non-relapse mortality (NRM) after allogeneic stem cell transplantation (alloSCT). By contrast, disease relapse remains the most frequent cause of treatment failure and death. Due to both their antimyeloma effect and immunomodulatory properties, novel drugs could imp...
Few approaches have been made toward exploring autologous NK cells in settings of cancer immunotherapy. Here, we demonstrate the feasibility of infusing multiple doses of ex vivo activated and expanded autologous NK cells in patients with multiple myeloma (MM) post-autologous stem cell transplantation. Infused NK cells were detected in circulation...
Introduction: In oncology clinical trials, overall survival (OS) is considered the gold standard efficacy endpoint. However, in multiple myeloma, the prolonged survival times and availability of multiple salvage therapies render it difficult to rely on OS as a primary endpoint. Instead, progression-free survival (PFS) or clinical response can be a...
Introduction: The phase 3 MAIA study (NCT02252172) evaluated the addition of daratumumab (D) to lenalidomide and dexamethasone (Rd) in patients (pts) with transplant-ineligible newly diagnosed multiple myeloma (NDMM). At a median follow-up of 56.2 months, D-Rd prolonged progression-free survival (PFS) and overall survival (OS) versus Rd alone, desp...
Introduction: Multiple myeloma (MM) is a chronic hematologic malignancy with a high symptom burden that can have a substantial negative impact on patients' (pts) health-related quality of life (HRQoL). The introduction of novel triplet regimens for newly diagnosed MM (NDMM) has extended progression-free survival (PFS) and overall survival (OS); how...
Introduction: Immunotherapies are gaining more and more importance in the treatment of multiple myeloma (MM). Antibodies directed against MM antigens like CD38, SLAMF7 or BCMA are used either in their natural form, conjugated to drugs, or in the form of bispecific T-cell engagers. Cellular therapies make use of cytotoxic lymphocytes, i.e. T cells o...
Introduction: Teclistamab (JNJ-64007957) is a T-cell redirecting, bispecific IgG4 antibody that targets both B-cell maturation antigen (BCMA) and CD3 receptors to induce T-cell mediated cytotoxicity of BCMA-expressing myeloma cells. Teclistamab is under investigation in MajesTEC-1, an ongoing phase 1/2 study in patients (pts) with heavily pretreate...
Introduction: Daratumumab (DARA) is a human monoclonal IgGκ monoclonal antibody targeting CD38 with a direct on-tumor and immunomodulatory mechanism of action. DARA is approved as monotherapy or in combination with standard-of-care regimens for the treatment of relapsed or refractory multiple myeloma (RRMM). The phase 1b 3-part PAVO study investiga...
Objective
We investigated the efficacy and safety of carfilzomib‐containing induction before salvage high‐dose melphalan with autologous stem‐cell transplantation (salvage ASCT) and maintenance with carfilzomib and dexamethasone after salvage ASCT in multiple myeloma.
Methods
This randomised, open‐label, phase 2 trial included patients with first...
Background
In the primary analysis of the phase 3 MAIA trial (median follow-up 28·0 months), a significant improvement in progression-free survival was observed with daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in transplantation-ineligible patients with newly diagnosed multiple myeloma. Here, we repor...
Background
The objective of this study was to investigate if there are differences in survival for Multiple myeloma (MM) patients in Sweden depending on health care region and early use of modern therapies
Method
Cohorts (labelled A-F) were defined by the six healthcare regions in Sweden. Modern initial therapies were defined as bortezomib in comb...
Introduction
In the primary analysis of MAIA, daratumumab (DARA) plus lenalidomide and dexamethasone (D-Rd) reduced the risk of disease progression or death by 44% vs lenalidomide and dexamethasone (Rd) in transplant-ineligible patients (pts) with newly diagnosed multiple myeloma (NDMM). Here, we report the updated efficacy and safety of D-Rd vs Rd...
Context
Daratumumab plus standard-of-care (SOC) showed superior efficacy vs SOC for patients with TIE-NDMM (phase 3 ALCYONE, MAIA, and CASSIOPEIA; primary analyses). In ALCYONE, after longer follow-up, adding daratumumab to bortezomib, melphalan, and prednisone significantly reduced the risk of death by 40%. In MAIA (primary analysis), D-Rd reduced...
Background
There is a need for novel therapies for relapsed or refractory multiple myeloma, and B-cell maturation antigen (BCMA) is a validated target. Teclistamab is a bispecific antibody that binds BCMA and CD3 to redirect T cells to multiple myeloma cells. The aim of the MajesTEC-1 study was to evaluate the safety, tolerability, and preliminary...
8007
Background: BCMA-targeted immunotherapies offer considerable promise for relapsed/refractory MM. Teclistamab (JNJ-64007957) is a BCMA × CD3 bispecific IgG4 antibody that redirects CD3+ T cells to BCMA-expressing MM cells. We present updated results of patients (pts) treated at the recommended phase 2 dose (RP2D) in the first-in-human phase 1 s...
Approximately 20% of newly diagnosed multiple myeloma (NDMM) patients harbor t(11;14), a marker of inferior prognosis, resulting in up‐regulation of CCND1. These patients respond to BCL2 inhibitor experimental drug venetoclax. Furthermore, t(11;14) is reported to be associated with increased BCL2/MCL1 ratio. We investigated the use of venetoclax (4...
Serum and urine protein electrophoresis (sPEP/uPEP) are the standard methods for monitoring of multiple myeloma (MM). However, a method of detection with shorter half-life, such as serum-free light chain (FLC), could detect the response or progression earlier. In total, 450 MM patients were assessed in first, second, and third line. Response and pr...
The phase 3 COLUMBA study demonstrated noninferiority of subcutaneous daratumumab (DARA SC) to intravenous daratumumab (DARA IV) in relapsed or refractory multiple myeloma. We present a subgroup analysis of Asian patients from COLUMBA. Eligible patients had ≥ 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug, o...
Belantamab mafodotin (belamaf) is a BCMA-targeted antibody–drug conjugate recently approved as monotherapy for adults with relapsed/refractory multiple myeloma who have received ≥4 prior therapies. Belamaf binds to BCMA and eliminates myeloma cells by multimodal mechanisms of action. The cytotoxic and potential immunomodulatory properties of belama...
This Policy Review presents the International Myeloma Working Group's clinical practice recommendations for the treatment of relapsed and refractory multiple myeloma. Based on the results of phase 2 and phase 3 trials, these recommendations are proposed for the treatment of patients with relapsed and refractory disease who have received one previou...
Introduction:
Treatment-induced peripheral neuropathy (TIPN) is a complication of multiple myeloma (MM) treatment.
Objective:
This real-world, retrospective study used electronic medical record (EMR) data from 3 Swedish clinics to assess the occurrence and economic burden of TIPN in patients with MM.
Methods:
Eligible patients had an MM diagno...
Introduction
Novel drugs and drug combinations have improved outcomes for multiple myeloma patients. However, subgroups of patients still have a poor progression‐free survival (PFS) and overall survival (OS). In an attempt to identify how the novel drugs affect the outcome in standard‐risk and high‐risk patients, respectively, we have investigated...
PurposeThe phase III COLUMBA study evaluated daratumumab (DARA) intravenous (IV) and subcutaneous (SC) in patients with relapsed or refractory multiple myeloma. Here, we report patient-reported satisfaction with therapy (SWT) in COLUMBA.MethodsDARA IV or DARA SC was administered weekly (cycles 1–2), every 2 weeks (cycles 3–6), and every 4 weeks (cy...
PURPOSE
To evaluate the effects of daratumumab, lenalidomide, and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) on patient-reported outcomes (PROs) in the phase III MAIA study.
PATIENTS AND METHODS
PROs were assessed on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item and t...
Introduction
Autologous stem cell transplantation (ASCT) combined with novel agents is considered as the standard treatment for eligible patients < 70(-75) years of age with multiple myeloma (MM). The number of induction cycles is usually 4-6 followed by ASCT, consolidation and maintenance. The role of consolidation is still under debate especially...
Background: MM inevitably relapses and becomes refractory to treatment, representing a patient (pt) population with unmet needs. Teclistamab (JNJ-64007957) is a bispecific BCMA x CD3 antibody that induces T cell-mediated cytotoxicity against BCMA-expressing MM cells. Previously presented results from an ongoing study of teclistamab in RRMM (NCT0314...
Introduction: Single-agent belamaf (GSK2857916), a B-cell maturation antigen-targeting antibody-drug conjugate, induced deep and durable responses in patients with RRMM, with a manageable safety profile with 13 months of follow-up (DREAMM-2; NCT03525678; Lonial et al, ASCO 2020, Poster 436). A platform trial design allows efficient evaluation of be...
Introduction: Due to its heterogenous nature including evolving mutations, multiple myeloma (MM) is still an incurable disease. Several novel agents have been introduced during the last decade resulting in prolonged median overall survival (OS) up to 7-8 years. Nevertheless, disease relapse is expected and eventually all patients will end up with r...
We report the population pharmacokinetic (PK) and exposure-response analyses of a novel subcutaneous formulation of daratumumab (DARA) using data from 3 DARA subcutaneous monotherapy studies (PAVO Part 2, MMY1008, COLUMBA) and 1 combination therapy study (PLEIADES). Results were based on 5159 PK samples from 742 patients (DARA 1800 mg subcutaneousl...
Epidemiological studies have demonstrated an increased incidence of MDS in patients with plasma cell disorder (PCD) i.e. multiple myeloma (MM) or MGUS and several case reports / series of co-occurring MDS and PCD have been published. The underlying pathogenesis for this condition, and if the two diseases share a common genetic lesion remains unknow...
Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant clonal plasma cell disorder, with a 1% yearly risk of progression to multiple myeloma (MM). Evolution of M‐spike and serum free light chain (sFLC) during follow‐up could identify patients at high risk of progression. In this region‐wide study, including 4756 individuals, 98...
COVID‐19 has emerged as a global pandemic. Cancer patients have been reported to be at higher risk for adverse outcome of COVID‐19. Studies are ongoing to decipher the risk factors and risk groups among cancer patients as well as strategies to refine treatment approaches. Here, we report eight patients with multiple myeloma that underwent immunomod...
Background
Daratumumab showed encouraging efficacy as monotherapy in patients with heavily pretreated multiple myeloma in the GEN501 and SIRIUS studies. Here we report a pooled, post-hoc final analysis of these two studies.
Methods
GEN501 was an open-label, multicentre, phase 1–2, dose escalation and expansion study done in the Netherlands, the US...
Background
Little is reported on the real‐life impact of daratumumab in relapsed and/or refractory multiple myeloma patients (RRMM). We analyzed a cohort of 156 patients who received daratumumab as a single agent concerning ECOG status, eGFR, cytogenetics, lines of prior treatment, and their impact on survival.
Results
Eighty‐two (53%) patients we...
100
Background: Teclistamab (JNJ-64007957) is a bispecific BCMA x CD3 antibody that induces T cell-mediated cytotoxicity against BCMA-expressing myeloma cells. Initial results from an ongoing study of teclistamab in RRMM (NCT03145181) are presented. Methods: Pts have MM and are RR to standard therapies. Primary objective for part 1 is to identify a...
8537
Background: Intravenous DARA (DARA IV) is approved for the treatment of MM. In Part 2 of PAVO, DARA SC, a concentrated, pre-mixed SC co-formulation of DARA and recombinant human hyaluronidase PH20 (rHuPH20), was well tolerated, with a low infusion-related reaction (IRR) rate, and showed consistent serum concentrations and similar efficacy to D...
Intravenous daratumumab is approved for the treatment of multiple myeloma. In Part 1 of the PAVO study, a mix-and-deliver subcutaneous formulation of daratumumab with recombinant human hyaluronidase PH20 (rHuPH20) was well tolerated, with low rates of infusion-related reactions and similar efficacy to intravenous daratumumab. Part 2 of PAVO evaluat...
Background
Intravenous daratumumab for treatment of patients with multiple myeloma involves a lengthy infusion that affects quality of life, and infusion-related reactions are common. Subcutaneous daratumumab is thought to be easier to administer and to cause fewer administration-related reactions. In this study (COLUMBA), we tested the non-inferio...
Objective
We describe survival in patients with oligo‐ and non‐secretory multiple myeloma (MM). We refer to the whole group as non‐measurable MM and compare it with secretory MM.
Methods
Oligo‐secretory MM was defined as M protein in serum <10 g/L and M protein in urine <200 measured as mg/day, mg/liter or mg/mmol creatinine. If patients had no M...
Plerixafor plus granulocyte-colony stimulating factor (G-CSF) enhances the mobilization of hematopoietic stem cells (HSCs) for collection and subsequent autologous hematopoietic stem cell transplantation (HSCT) in patients with multiple myeloma (MM). This international, multicenter, noninterventional registry study (NCT01362972), evaluated long-ter...
Immunoglobulin light-chain amyloidosis (AL) is a disease with limited treatment options due to the frailty of patients caused by organ damage. Since the clonal plasma cells often contain the cytogenetic aberration t(11;14), the Bcl-2 inhibitor venetoclax is suggested to have a role in the treatment of AL. Here, we report of a heart-transplanted pat...
Introduction: Daratumumab (DARA) is a human, CD38-targeted, IgG1κ monoclonal antibody approved as monotherapy in heavily pretreated relapsed/refractory multiple myeloma (RRMM) and in combination with standard-of-care regimens for transplant-ineligible NDMM and RRMM. The addition of DARA to standard-of-care regimens in phase 3 studies has consistent...
Introduction: The intravenous (IV) formulation of human CD38 mAb DARA is approved in many countries as monotherapy or in combination with standard-of-care regimens for treatment of multiple myeloma (MM).
To reduce patient (pt)/provider burden and improve safety, a DARA SC co-formulation (1800 mg + recombinant human hyaluronidase PH20 [rHuPH20; 2000...
Introduction: DARA, a human CD38 monoclonal antibody (mAb), is approved for intravenous (IV; 16 mg/kg) administration as a single agent or in combination with standard-of-care regimens for treatment of multiple myeloma. To reduce patient and provider burden and improve safety, a subcutaneous (SC) co-formulation of DARA (flat dose of 1,800 mg, ~70%...
INTRODUCTION: Daratumumab (DARA), a human IgGκ monoclonal antibody targeting CD38, is approved for intravenous (IV; 16 mg/kg) administration as a single agent or in combination with standard-of-care regimens for treatment of multiple myeloma (MM).To improve safety and reduce patient and healthcare provider burden, a subcutaneous (SC) formulation of...
Introduction
The use of autologous haematopoietic cell transplantation (auto-HCT) in the treatment of myeloma (MM) has greatly increased over the last twenty-five years. There are, however, few large datasets detailing the overall trends in transplant use, patient selection, induction regimen, choice of mobilisation regimen, stem cell yield, respon...
Background: Salvage autologous stem cell transplantation (ASCT) is used in selected patients with relapsed multiple myeloma after up-front ASCT. However, there are limited data on the optimal induction therapy before salvage ASCT. There is strong support for the use of maintenance therapy after upfront ASCT in newly diagnosed multiple myeloma where...
