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Urvi A. Shah, MD, Assistant Attending at Memorial Sloan Kettering Cancer Center and Assistant Professor at Weill Cornell Medicine, New York, moderated the session where the MagnetisMM trial updates1,2 were reported and was interviewed by The ASCO Post. Elranatamab vs Teclistamab Dr. Shah noted...
The promise of bispecific monoclonal antibodies in multiple myeloma continues to heighten as yet another one appears to be active. In a study reported at the 2022 American Society of Hematology (ASH) Annual Meeting and Exposition,1 almost two-thirds of patients with triple-refractory disease who...
As reported in the Journal of Clinical Oncology by Pieter Sonneveld, MD, PhD, of Erasmus MC Cancer Institute, Rotterdam, the Netherlands, and colleagues, the final overall survival analysis of the phase III CASTOR trial has shown a significant benefit of the addition of daratumumab to...
In a retrospective study of the real-world use of idecabtagene vicleucel reported in the Journal of Clinical Oncology, Hansen et al found that response rates and toxicity in patients with relapsed or refractory multiple myeloma were comparable to those in the pivotal phase II KarMMa trial; the...
The 2022 American Society of Hematology (ASH) Annual Meeting and Exposition was full of interesting abstracts in multiple myeloma. In addition to full coverage of several important presentations, The ASCO Post offers readers quick takes on some studies that could be practice-changing and others...
In the phase I/II MonumenTAL-1 trial, the novel bispecific antibody talquetamab produced responses in more than 70% of heavily pretreated patients with multiple myeloma.1 Of note, the safety profile confirmed results of the phase I portion of the study (recently published in TheNew England Journal...
As reported in The Lancet Oncology by Dominik Dytfeld, MD, PhD, and colleagues, an unplanned interim analysis of the phase III ATLAS trial has shown improved progression-free survival with carfilzomib, lenalidomide, and dexamethasone (KRd) vs lenalidomide alone as maintenance after autologous stem...
As reported in the Journal of Clinical Oncology by Meletios A. Dimopoulos, MD, and colleagues, the final overall survival analysis of the pivotal phase III POLLUX trial has shown a significant benefit with the addition of daratumumab to lenalidomide and dexamethasone after a median follow-up of...
In a prespecified analysis of the Italian phase II FORTE trial reported in The Lancet Oncology, Mina et al identified outcomes associated with the number of high-risk cytogenetic abnormalities (HRCAs) across treatment groups receiving carfilzomib-containing induction, consolidation, and maintenance ...
Paul G. Richardson, MD, of the Dana-Farber Cancer Institute, discusses preliminary results from the dose-expansion phase of the CC-92480-MM-001 Trial, which showed promising efficacy in patients with relapsed and refractory multiple myeloma, including those with prior BCMA-targeted therapies. Patients in these two groups had an overall response rate of 40% and 50%, respectively. The results support the development of mezigdomide, currently being evaluated in combination with standard therapies in multiple myeloma as part of a large, ongoing phase I/II trial (NCT03989414) and planned phase III studies (Abstract 568).
The novel drug modakafusp alfa has shown early promise in combating relapsed/refractory multiple myeloma, according to new findings presented by Vogl et al at the 2022 American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 565). Background Modakafusp alfa is a fusion protein...
The novel MinimuMM-seq technique may make it possible to detect tumor cells in individuals at higher risk for multiple myeloma, assess the risk of disease progression in patients with myeloma, and track genetic changes in tumor cells over time from a single blood sample, according to a new study...
Jiye Liu, PhD, of Dana-Farber Cancer Institute, discusses study findings that demonstrate KDM6A regulates CD38 and CD48 expression in multiple myeloma. Dr. Liu’s team validated combination treatment with an FDA-approved EZH2 inhibitor plus daratumumab, which can overcome daratumumab resistance in preclinical multiple myeloma models, providing the rationale for combination clinical trials to improve patient outcome (Abstract 148).
Francesco Maura, MD, of the University of Miami, Sylvester Comprehensive Cancer Center, discusses his team’s findings in which they defined a comprehensive catalogue of genomic determinants of response to DKRd (carfilzomib, lenalidomide, dexamethasone) in newly diagnosed multiple myeloma. The researchers have identified a number of new genomic alterations that explain resistance to the agents currently used in combination regimens (Abstract 470).
Eileen M. Boyle, MD, PhD, of the Perlmutter Cancer Center, NYU Langone Health, discusses Fc-mediated antibody effector function, inflammation resolution, and oligoclonality and their role in predicting sustained measurable residual disease negativity in patients with newly diagnosed multiple myeloma who were treated with immunotherapy regimens. For the first time, an analysis of T-cell receptors shows that oligoclonal profiles seen on treatment may influence the fitness of the immune response (Abstract 100).
Julie Côté, MD, of CHU de Québec–Université Laval, discusses findings from the Canadian Myeloma Research Group database, which showed that integrating bortezomib and lenalidomide into the autologous stem cell transplant (ASCT) sequence produces a median overall survival rate ≥ 10 years in most patients with newly diagnosed multiple myeloma. These observations highlight the contribution of post-ASCT maintenance, particularly lenalidomide given until disease progression, when used in multiple patient groups including those with and without high risk, as well as those requiring a second induction regimen (Abstract 117).
In an early-phase trial, nearly three-quarters of patients who received talquetamab—a first-in-class, off-the-shelf, T-cell–redirecting bispecific antibody targeting both the GPRC5D and CD3 receptors—for relapsed or refractory multiple myeloma saw a significant reduction in cancer burden within a...
On October 25, 2022, the bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager teclistamab-cqyv was granted accelerated approval for the treatment of adults with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome...
As reported in the Journal of Clinical Oncology by Sonneveld et al, the final overall survival analysis of the phase III CASTOR trial has shown a significant overall survival benefit with daratumumab plus bortezomib/dexamethasone (D-Vd) vs bortezomib/dexamethasone alone (Vd) in patients with...
In a study reported in the Journal of Clinical Oncology, Lannes et al found that single-cell genomics could identify the presence of high-risk copy number abnormalities (CNAs) in small subclonal populations at diagnosis of multiple myeloma in many patients. The investigators stated, “Multiple...
On October 25, 2022, the bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager teclistamab-cqyv was granted accelerated approval for the treatment of adults with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome...
For many patients who have smoldering myeloma, early treatment can slow or delay the disease’s progression to multiple myeloma, according to a new study published by Sklavenitis-Pistofidis et al in Cancer Cell. Investigators demonstrated that changes in immune system cells may indicate which cases...
In a study reported in the Journal of Clinical Oncology, Jelinek et al provided evidence that a threshold of ≥ 2% circulating tumor plasma cells (CTCs) defines the presence of plasma cell leukemia (PCL)-like multiple myeloma. As stated by the investigators, “Primary PCL is the most aggressive...
Researchers have identified potential therapies to treat patients with multiple myeloma whose cancer has relapsed following chimeric antigen receptor (CAR) T-cell therapy, according to a novel study published by Van Oekelen et al in Blood. CAR T-cell therapy has been a revolutionary treatment for...
In a Chinese phase II trial (CARTIFAN-1) reported in the Journal of Clinical Oncology, Mi et al found that the anti–B-cell maturation antigen chimeric antigen receptor (CAR) T-cell therapy ciltacabtagene autoleucel was active in patients with relapsed or refractory multiple myeloma. Study Details...
On October 25, the U.S. Food and Drug Administration (FDA) granted accelerated approval to teclistamab-cqyv (Tecvayli), the first bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager, for adult patients with relapsed or refractory multiple myeloma who have received at least four...
In a single-institution phase I study reported in The New England Journal of Medicine, Sham Mailankody, MBBS, and colleagues found that chimeric antigen receptor (CAR) T cells targeting G protein–coupled receptor, class C, group 5, member D (GPRC5D) were active in heavily pretreated patients with...
From microchips to automobiles, people in the United States are experiencing shortages of all kinds of products, and oncology treatments are no exception. In particular, shortages related to chimeric antigen receptor (CAR) T-cell therapy have been reported, most acutely, for B-cell maturation...
New computed tomography (CT) technology paired with artificial intelligence (AI)-based noise reduction may offer superior detection of bone disease associated with multiple myeloma at lower radiation doses than conventional CT, according to a recent study published by Baffour et al in Radiology....
“I think the biggest innovations of the 21st century will be at the intersection of biology and technology. A new era is beginning!” —Steve Jobs Relapsed and refractory multiple myeloma remains a treatment challenge. Promising responses have been demonstrated with bispecific antibodies, with a...
Mount Sinai researchers have published results that show alternate therapeutic options for patients with multiple myeloma after first-line treatment with bispecific antibodies fails. While new T cell–based immunotherapies, or “T-cell redirection” therapies, such as chimeric antigen receptor (CAR)...
In a phase I trial reported in the Journal of Clinical Oncology, D’Souza et al found that the B-cell maturation antigen (BCMA) x CD3 bispecific T-cell redirecting antibody ABBV-383 was active in patients with relapsed or refractory multiple myeloma. Study Details In the ongoing trial, 124 patients...
The randomized phase II GRIFFIN study evaluated the investigational use of daratumumab in combination with lenalidomide, bortezomib, and dexamethasone (RVd), followed by maintenance therapy with daratumumab and lenalidomide, compared to RVd followed by maintenance therapy with lenalidomide alone,...
Currently, there are two U.S. Food and Drug Administration–approved chimeric antigen receptor (CAR) T-cell therapies targeting the B-cell maturation antigen (BCMA) for adult patients with relapsed or refractory multiple myeloma: idecabtagene vicleucel and citacabtagene autoleucel. However, although ...
In an observational seroprevalence study reported in Blood Cancer Journal, Zeig-Owens et al found an elevated prevalence of myeloma precursor disease—monoclonal gammopathy of undetermined significance (MGUS)—in a cohort of World Trade Center (WTC) disaster–exposed rescue and recovery workers....
In a study reported in the Journal of Clinical Oncology, Casey et al found that most U.S. minority populations were underrepresented in clinical trials leading to U.S. Food and Drug Administration approval of drugs for treating leukemias and multiple myeloma. Study Details The investigators...
As reported in the Journal of Clinical Oncology by Meletios A. Dimopoulos, MD, and colleagues, the final overall survival analysis of the phase II ELOQUENT-3 trial showed significant benefit with the addition of elotuzumab to pomalidomide and dexamethasone (EPd) vs pomalidomide and dexamethasone...
About 3 years ago, researchers from Dana-Farber Cancer Institute launched PROMISE (Predicting Progression of Developing Myeloma in a High-Risk Screen Population; ClinicalTrials.gov identifier NCT03689595), a large, ambitious screening study to identify individuals at high risk of developing...
In a phase II trial reported in JAMA Oncology, Derman et al found that a measurable residual disease (MRD)-adapted strategy with elotuzumab (Elo) plus carfilzomib, lenalidomide, and dexamethasone (KRd) was associated with high rates of stringent complete response and MRD-negative status in patients ...
The invited discussant of the ATLAS trial, Peter M. Voorhees, MD, Professor of Medicine, Chief of the Plasma Cell Disorders Division, at Levine Cancer Institute and Atrium Health/Wake Forest Baptist in North Carolina, applauded the very good outcomes achieved in the study.1 However, he posed the...
For newly diagnosed patients with multiple myeloma participating in the international phase III ATLAS trial, use of carfilzomib, lenalidomide, and dexamethasone (KRd) as maintenance therapy after induction and autologous stem cell transplantation (ASCT) significantly reduced the risk of disease...
Researchers studying the molecular landscape of over 500 patients with relapsed or refractory multiple myeloma discovered a prevalence of activated key oncogenic pathways in these patients—much more than previously thought. Upward of 45% to 65% of NF-κB and RAS/MAPK pathways each had alterations....
Caregivers for patients with multiple myeloma may suffer from higher rates of anxiety and depression than patients themselves, according to a new study published by O’Donnell in Blood Advances. Although medical professionals have long acknowledged the toll a serious or terminal diagnosis can have...
In patients with multiple myeloma exposed or refractory to three standard therapies, treatment with the bispecific antibody teclistamab produced strong and durable responses in the phase I/II MajesTEC-1 study.1 The results of weekly subcutaneous dosing of teclistamab in 165 patients were presented...
A radiologist by training, I knew the minute I saw the results from my chest x-ray that I had multiple myeloma. In 2015, I was semiretired and had just taken up the game of golf. After making a big swing at the ball, I instantly felt pain in my ribs and thought I had either pulled an intercostal...
In a study reported in the Journal of Clinical Oncology, Bertamini et al found that higher levels of circulating tumor cells (CTCs) at diagnosis were associated with poorer progression-free and overall survival in transplant-eligible patients with newly diagnosed multiple myeloma. The prognostic...
In a study reported in the Journal of Clinical Oncology, Garcés et al found that increasing levels of circulating tumor cells (CTCs) at diagnosis were associated with poorer outcomes in newly diagnosed patients with transplant-eligible multiple myeloma, and that inclusion of CTCs in a risk model...
Researchers have, for the first time, identified genes that may predict response to a therapy for a blood cancer that can have serious side effects for some patients. The therapy, selinexor, is part of the treatment armamentarium for multiple myeloma, but the ability to target its use to patients...
In an analysis reported in a research letter in JAMA Oncology, Nguyen et al identified postmarketing cases of ocular toxicity in patients receiving daratumumab in the United States. Daratumumab is a CD38-directed monoclonal antibody that was initially approved in 2015 for the treatment of multiple...
As reported in the Journal of Clinical Oncology by D’Agostino et al in the European Myeloma Network, a second revision (R2-ISS) of the Revised International Staging System (R-ISS) incorporates a risk scoring system that permits delineation of four prognostic risk groups in newly diagnosed multiple...