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July 2013 - August 2020
Publications
Publications (827)
In the MAIA study, daratumumab plus lenalidomide and dexamethasone (D-Rd) improved progression-free survival (PFS) and overall survival (OS) versus lenalidomide and dexamethasone (Rd) alone in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). We report updated efficacy and safety from MAIA (median follow-up, 64.5 months),...
Current prognostic scores in multiple myeloma (MM) currently rely on disease burden and a limited set of genomic alterations. Some studies have suggested gene expression panels may predict clinical outcomes, but none are presently utilized in clinical practice. The tyrosine kinase WEE1 is a critical cell cycle regulator during the S-phase and G2M c...
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...
Frontline daratumumab-based triplet and quadruplet standard-of-care regimens have demonstrated improved survival outcomes in newly diagnosed multiple myeloma (NDMM). For patients with transplant-ineligible NDMM, triplet therapy with either daratumumab plus lenalidomide and dexamethasone (D-Rd) or bortezomib, lenalidomide and dexamethasone (VRd) is...
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...
Idecabtagene vicleucel (ide-cel) is an anti-BCMA CAR-T cell therapy approved for patients with relapsed/refractory multiple myeloma (RRMM) after 2 prior lines of therapy. There is limited data on outcomes of CAR T in older adults and frail patients with RRMM. In this study, we utilized data from the Center for International Blood and Marrow Transpl...
MCARH109 is a first-in-class G protein–coupled receptor, class C, group 5, member D (GPRC5D)-targeted chimeric antigen receptor (CAR) T-cell therapy for patients with relapsed/refractory multiple myeloma. This phase I clinical trial included 17 patients and determined that MCARH109 is safe at a maximum tolerated dose of 150 × 10 ⁶ CAR T cells. In t...
In newly diagnosed multiple myeloma (NDMM), measurable residual disease (MRD) status is prognostically important, but its role in treatment-decisions remains unclear. In a phase II trial (NCT04113018), we assessed daratumumab, carfilzomib, lenalidomide and dexamethasone (Dara-KRd) induction followed by a next generation sequencing (NGS) based MRD-a...
Ionizing radiotherapy (RT) is a widely used palliative and curative treatment strategy for malignancies. In solid tumors, RT-induced double strand breaks lead to the accumulation of indels, and their repair by non-homologous end-joining has been linked to the ID8 mutational signature in resistant cells. However, the extent of RT-induced DNA damage...
Background
Poor diet quality lacking plant-based foods, elevated body mass index (BMI), insulin resistance, microbiome dysbiosis, as well as inflammation have all been implicated in progression from monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) to MM. Whether a dietary intervention can delay progres...
Multiple myeloma (MM) is an incurable cancer of plasma cells with nearly 70% of all new diagnoses occurring in adults aged ≥ 65 years. For older adults, medical comorbidities and functional deficits become increasingly more prevalent with increased age and can impact disease outcomes and survival. There are unmet medical needs in this vulnerable pa...
Background: Systemic therapies for MM have advanced considerably. Yet, the use of RT has remained stagnant due to heterogeneous integration into modern treatments. Here we report on three cohorts of MM RT patients treated at a large cancer center over 10 years, assessing trends of RT engagement, radiographic and biochemical outcomes, and potential...
Introduction: Teclistamab (Tec) is the first approved BCMA x CD3 bispecific antibody for the treatment of triple-class-exposed patients with relapsed/refractory multiple myeloma (RRMM) based on the pivotal MajesTEC-1 study. Tec was associated with high overall response rate (ORR) of 63% in heavily pretreated patients. After a longer follow-up of 30...
Introduction
Maintenance strategies in newly diagnosed multiple myeloma (NDMM) are evolving given the availability of novel single agent and combination strategies aimed at improving progression free survival (PFS) without worsening quality of life. Current standard practice is indefinite lenalidomide (len) maintenance given its PFS and overall sur...
Introduction
Multiple Myeloma (MM) disproportionately affects Black populations. Modifiable risk factors, such as elevated body mass index (BMI) and diabetes mellitus (DM) are linked to increased MM risk. Furthermore, these risk factors also disproportionately affect Black compared to White populations. Therefore, we aim to calculate the MM inciden...
Introduction
APOBEC mutational signatures are prominent in newly diagnosed multiple myeloma (NDMM), driven primarily by the enzymes APOBEC3A (A3A) and APOBEC3B (A3B). The activity of these enzymes varies significantly among patients, with some exhibiting no detectable mutations while others show high levels of APOBEC-induced mutations, termed hyper...
Introduction
Induction therapy (Tx) followed by ASCT and lenalidomide (LEN) maintenance is the standard of care in transplant-eligible pts with NDMM. Pts who have suboptimal response after front-line ASCT, however, have an increased risk of progression or death. Ide-cel demonstrated significantly improved median progression-free survival (PFS) and...
Background:
Despite recent major advances, multiple myeloma (MM) remains incurable using therapies that are currently available to patients. There are no available/approved targeted therapies for MM that allow for individualized therapeutic approaches to the disease. Fifteen to 20% of newly diagnosed MM patients have a translocation of chromosomes...
Introduction/Background:
Chimeric antigen receptor (CAR)-modified T cells targeting BCMA have shown high response rates and durable remissions in patients with relapsed or refractory multiple myeloma (RRMM). Since this innovative therapy leverages the patient's own immune system, T cell fitness prior to CAR-T therapy is increasingly important. Acce...
Background
Multiple myeloma (MM) patients often develop bone disease, predisposing them to skeletal-related events (SREs). Renal impairment (RI), a cardinal feature of MM, further complicates treatment strategies. Denosumab, a bone-directed immunotherapy, has demonstrated non-inferiority to zoledronic acid but its efficacy and safety in patients wi...
Background: Data from the ASH Research Collaborative COVID-19 Registry for Hematology demonstrated that patients with multiple myeloma and other immune compromise had elevated risk for severe complications from COVID-19 infection. To address current evidence gaps and to demonstrate proof of concept for a pandemic preparedness and response network,...
Introduction:
Multiple myeloma (MM) is a disease of the elderly with a median age of 69 years at diagnosis. In addition to advanced age, many of these patients are frail with pre-existing comorbidities and have been historically excluded from clinical trials evaluating cellular immunotherapy including bispecific antibodies (BsAb) for relapsed refra...
Introduction: The treatment paradigm for transplant-eligible (TE) patients (pts) with newly diagnosed multiple myeloma (NDMM) is shifting from frontline (FL) triplet (e.g., bortezomib [V], lenalidomide [R], and dexamethasone [d]) towards FL quadruplet regimens based on the pivotal PERSEUS and GRIFFIN trials, which showed that addition of daratumuma...
Introduction
Ionizing radiotherapy (RT) is a mainstay in the local control of lymphoid malignancies. It introduces DNA double-strand breaks (DSB) that result in cell death unless repaired prior to cell division. Resulting mutations are measurable as mutational signatures with whole genome sequencing (WGS). Importantly, detection of a therapy-induce...
Background: The COVID-19 pandemic had an outsized impact on individuals with immune compromise, such as multiple myeloma, leading to increased rates of severe COVID, hospitalization, and death in these groups. The pandemic also demonstrated the need for rapid and efficient evidence generation to address rapidly changing medical needs and accelerate...
Background:
Commercially available anti-BCMA CAR T cells have revolutionized treatment for patients with relapsed/refractory multiple myeloma (MM). However, most patients ultimately relapse. We therefore evaluated strategies to combine salvage autologous (autoHCT) or allogeneic hematopoietic stem cell transplant (alloHCT) with commercial CAR T cell...
Introduction: Understanding patient preferences and decision-making processes is crucial in managing relapsed multiple myeloma (RRMM). Shared decision-making has become a key element of patient-centered care, allowing patients to collaborate with healthcare providers in choosing treatments that align with their health and quality of life goals. Thi...
Background: Contemporary questions about treatment and outcomes of patients (pts) living with multiple myeloma (MM) demand efficient and timely evidence generation methods, where real-world/ everyday practice data can play an important role. Relevant potential applications include understanding and addressing disparities in treatment access, mitiga...
Introduction/Background: Talquetamab (Talq) is a first-in-class bispecific T-cell engager antibody directed against G protein-coupled receptor class C group 5 member D (GPRC5D), approved to treat patients with relapsed/refractory multiple myeloma (RRMM) after at least 4 lines of therapy (including an immunomodulatory agent, a proteasome inhibitor a...
Introduction
The pathogenic role of somatic non-coding (nc) single nucleotide variants (SNVs) is underexplored in multiple myeloma (MM) and additional characterization of these regions has the potential to provide significant new insights into disease progression. To investigate the role of ncSNVs and their relationship with MM pathogenesis, we hav...
Background
Elevated body mass index (BMI) is a recognized risk factor for newly diagnosed multiple myeloma (NDDM), and extremes of BMI (underweight and obese) are associated with worse survival. Despite this, the clinical significance of BMI changes during induction therapy is poorly understood. The primary goal of this study was to identify patien...
INTRODUCTION: Improving outcomes for patients with African ancestry (AA) is a key healthcare aim, but it's unknown whether disparities arise primarily from differences in socioeconomic environment or tumor biology. In multiple myeloma (MM), studies have suggested that precursor conditions develop at a higher rate and earlier age in AA, with an exce...
Background: Growth of multiple myeloma (MM) beyond the bone marrow (BM) represents clinically aggressive disease and is associated with inferior therapy response. We hypothesize that genomic changes underlie the increasing BM independence seen from focal intra-medullary lesions (IMD) to para-medullary (PMD) and extra-medullary disease (EMD). To add...
Introduction: Infections cause significant morbidity among relapsed refractory multiple myeloma (RRMM) patients receiving chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies (BsAbs). Real-world infection data in patients receiving commercial BsAbs and CAR T-cell therapy as standard of care are lacking and necessary to understan...
Introduction
DREAMM-9 (NCT04091126) is an ongoing randomized Phase 1 dose optimization study evaluating belantamab mafodotin (belamaf) plus bortezomib, lenalidomide, and dexamethasone (VRd) in autologous stem cell transplant (ASCT)-ineligible newly diagnosed multiple myeloma (TI NDMM). A previous interim analysis reported no unexpected safety signa...
Background: CAR T-cell therapy (CAR-T) results in a unique spectrum of toxicities, affecting morbidity, mortality, and quality of life. Traditionally, immunotoxicities like cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are studied independently. However, the overall toxicity landscape of CAR-T is...
Introduction
Poor diet quality, elevated body mass index (BMI), insulin resistance, microbiome dysbiosis, inflammation as well as immune dysfunction have all been implicated in progression from monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) to multiple myeloma (MM). Plant-based diets have been associ...
Introduction: Talquetamab, a G protein-coupled receptor, class C group 5 member D (GPRC5D)-directed bispecific antibody (BsAb), was approved in August 2023 for patients with relapsed/refractory multiple myeloma (RRMM) who have received ≥4 prior lines of therapy, based on the results of the phase 1/2 MonumenTAL-1 trial. Here, we evaluated the real-w...
Purpose
Multiple myeloma (MM) is a hematological malignancy associated with a malignant proliferation of plasma cells. Although the disease is usually responsive to upfront therapies, MM still remains incurable. Current prognostic scores in MM (International Staging System; ISS, revised-ISS; R-ISS) rely on disease burden and a limited set of genomi...
Introduction: Ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel) are two chimeric antigen receptor (CAR) T-cell products targeting B-cell maturation antigen (BCMA) that have recently been approved for the treatment of relapsed/refractory multiple myeloma (RRMM) with 1-2 prior lines of therapy, based on the results of CARTITU...
Introduction: The achievement of minimal residual disease (MRD) negativity is associated with longer-term survival outcomes and has evolved into a strong prognostic clinical endpoint in MM. In the phase 3 CEPHEUS study, DARA in combination with VRd (D-VRd) significantly increased depth of response, including rates of overall MRD negativity, complet...
The introduction of chimeric antigen receptor T cells (CART) and bispecific T-cell engagers (TCE) has revolutionized the treatment landscape in patients with relapsed/ refractory multiple myeloma (RRMM). However, despite impressive responses reported to date, the mechanisms responsible for resistance or treatment failure remain inadequately determi...
Introduction: Multiple myeloma (MM) is a hematological malignancy characterized by a highly complex molecular landscape. Despite advancements in therapeutic strategies, patients identified as high-risk (HR), experience limited benefits from modern treatments. Various risk factors have been established to assess the risk in MM, with cytogenetic aber...
Introduction/Background: Chimeric antigen receptor (CAR)-T cell and bispecific antibody (BsAb) therapies demonstrated high response rates in relapsed/refractory multiple myeloma (RRMM), yet patients often experience significant toxicities. Data on the incidence, risk factors, and outcomes of acute kidney injury (AKI) following CAR T cell and BsAb t...
Introduction: MEZI, a novel, potent oral CELMoD™ agent, induces rapid and maximal degradation of Ikaros and Aiolos compared with immunomodulatory drugs (IMiDs®), resulting in direct tumoricidal and immunomodulatory effects in myeloma cells. The CA057-003 phase 1/2 trial (NCT05372354) is evaluating all-oral, novel-novel targeted triplet combination...
Introduction: Measurable residual disease negativity (MRD-) is predictive in newly diagnosed (ND) multiple myeloma (MM). However, the clinical significance of MRD resurgence (MRDres), where MRD- patients show re-emergence of MRD positivity (MRD+), is incompletely understood. Additionally, the significance of patient-specific immune profiling has no...
Background
B-cell maturation antigen (BCMA) directed therapies have demonstrated significant efficacy in relapsed/refractory multiple myeloma however treatments can still be optimized to improve the response rates. BCMA is cleaved from the cell surface through the enzyme gamma secretase. Pre-clinical suggest that adding a gamma secretase inhibitor...
What is this summary about?:
This summary describes the final analysis of the GRIFFIN study. In this study, participants were newly diagnosed with a type of blood and bone marrow cancer called multiple myeloma, had never received any treatment, and were able to undergo an autologous stem cell transplant. The GRIFFIN study looked at adding the drug...
Dexamethasone is a key component of induction for newly diagnosed multiple myeloma (NDMM) despite common toxicities including hyperglycemia and insomnia. In the randomized ECOG E4A03 trial, dexamethasone 40 milligrams (mg) once weekly was associated with lower mortality than higher doses of dexamethasone. However, the performance of dexamethasone d...
Current prognostic scores in multiple myeloma (MM) currently rely on disease burden and a limited set of genomic alterations. Some studies have suggested gene expression panels may predict clinical outcomes, but none are presently utilized in clinical practice. We therefore analyzed the MMRF CoMMpass dataset (N=659) and identified a high-risk group...
To comprehensively unravel the temporal relationship between initiating and driver events and its impact on clinical outcomes, we analyzed 421 whole-genome sequencing profiles from 382 patients. Using clock-like mutational signatures, we estimated a time lag of 2-4 decades between initiating events and diagnosis. In patients with hyperdiploidy, we...
Introduction
Ciltacabtagene autoleucel (cilta-cel) is a chimeric antigen receptor T-cell therapy approved for patients with relapsed/refractory multiple myeloma (RRMM). In the phase 3 trial, CARTITUDE-4 (NCT04181827), cilta-cel demonstrated improved efficacy vs. standard of care (SOC; daratumumab plus pomalidomide and dexamethasone [DPd] or pomalid...
Teclistamab is a B‑cell maturation antigen (BCMA)-directed bispecific antibody approved for the treatment of patients with triple-class exposed relapsed/refractory multiple myeloma. In the phase 1/2 MajesTEC-1 study, a cohort of patients who had prior BCMA-targeted therapy (antibody-drug conjugate [ADC] or CAR-T cell therapy) were enrolled to explo...
Multiple myeloma is a treatable, but currently incurable, hematological malignancy of plasma cells characterized by diverse and complex tumor genetics for which precision medicine approaches to treatment are lacking. The Multiple Myeloma Research Foundation's Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile s...
Artificial intelligence enabled interpretation of electrocardiogram waveform images (AI-ECG) can identify patterns predictive of future adverse cardiac events. We hypothesized such an approach, which is well described in general medical and surgical patients, would provide prognostic information with respect to the risk of cardiac complications and...
Optimal therapy for the growing number of patients with lenalidomide (LEN)-refractory multiple myeloma (MM) in first relapse remains poorly defined. We therefore undertook a randomized phase II study evaluating the efficacy and safety of combining the oral proteasome inhibitor ixazomib (IXA) with pomalidomide (POM) and dexamethasone (DEX) for this...
The randomized, phase 2 GRIFFIN study (NCT02874742) evaluated daratumumab plus lenalidomide/bortezomib/dexamethasone (D-RVd) in transplant-eligible newly diagnosed multiple myeloma (NDMM). We present final post hoc analyses (median follow-up, 49.6 months) of clinically relevant subgroups, including patients with high-risk cytogenetic abnormalities...
B-cell-maturation-antigen (BCMA)-directed therapies are highly active for multiple myeloma, but infections are emerging as a major challenge. In this retrospective, single-center analysis we evaluated infectious complications after BCMA-targeted chimeric-antigen-receptor T-cell therapy (CAR-T), bispecific-antibodies (BsAb) and antibody-drug-conjuga...
Despite being the mainstay of management for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), there is limited data regarding the impact of tocilizumab (TCZ) and corticosteroids (CCS) on chimeric antigen receptor (CAR) T-cell efficacy in multiple myeloma (MM). The present study aims to evaluate the...
Lenalidomide maintenance is associated with a significantly improved progression-free in patients with newly diagnosed multiple myeloma. Maintenance with lenalidomide is generally well tolerated; however, lenalidomide associated diarrhea is a common side effect and bile acid malabsorption has been suggested as an underlying mechanism. We conducted...
B-cell maturation antigen (BCMA)-targeting therapeutics have dramatically improved outcomes in relapsed/refractory multiple myeloma (RRMM). However, whether the mechanisms of resistance between these therapies are shared and how the identification of such mechanisms before therapy initiation could refine clinical decision-making remains undefined....
