Minimal Residual Disease (MRD)-Driven Cessation of Maintenance: Free from Drug Therapy in Multiple Myeloma (FREEDMM trial in progress)
Indefinite maintenance in MM with continuous lenalidomide carries both significant clinical and financial toxicity. We hypothesize that MRD could be used to predict a subset of patients who can safely stop maintenance therapy and enter into a disease surveillance phase. (Source: Biology of Blood and Marrow Transplantation)
Source: Biology of Blood and Marrow Transplantation - February 1, 2024 Category: Hematology Authors: Ana Avila Rodriguez, Danny Hadidi, Craig Hofmeister, John Quigley, Maria Zappia, Maxim Frolov, Elizaveta V Benevolenskaya, Matias Sanchez, Shrihari Kadkol, Douglas Sborov, Damiano Rondelli, Chukwuemeka Uzoka, Karen Sweiss Tags: 541 Source Type: research
Motixafortide Enables Consistent, Robust Hematopoietic Stem Cell Collection (HSC) across Populations with Increased Impaired HSC Mobilization: A Sub-Group Analysis of the Genesis Study
The clinical benefit of autologous hematopoietic stem cell transplant (ASCT) for multiple myeloma (MM) partly depends on the ability to collect sufficient hematopoietic stem cells (HSCs) from peripheral blood (PB). Risk factors for impaired HSC mobilization are increasingly common in patients with MM undergoing ASCT in the current treatment landscape, including advanced age, presence of cytopenias and prior exposure to radiation, lenalidomide and/or anti-CD38 monoclonal antibodies (mAb). Motixafortide is a novel high affinity CXCR4 antagonist indicated, in combination with G-CSF, for mobilization of HSCs to the PB for coll...
Source: Biology of Blood and Marrow Transplantation - February 1, 2024 Category: Hematology Authors: Zachary D Crees, Michael P. Rettig, Reyka Jayasinghe, Keith Stockerl-Goldstein, Sarah M Larson, Illes Arpad, Giuseppe Milone, Massimo Martino, Patrick J. Stiff, Douglas Sborov, Denise Pereira, Ivana N Micallef, Gemma Moreno-Jim énez, Gabor Mikala, Maria Tags: 537 Source Type: research
Cost per Responder Analysis of Patients with Lenalidomide-Refractory Multiple Myeloma Who Received Cilta-Cel from the Cartitude-4 Trial
Ciltacabtagene autoleucel (cilta-cel) is a chimeric antigen receptor-T cell (CAR-T) immunotherapy approved for patients (pts) 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 pomalidomide plus bortezomib and dexamethasone [PVd]) with an overall response rate (ORR) of 84.6% vs 67.3% and ≥complete response (CR) of 73.1% vs 21.8%. (Source: Biology of Blood and Marrow Transplantation)
Source: Biology of Blood and Marrow Transplantation - February 1, 2024 Category: Hematology Authors: Doris K Hansen, Xiaoxiao Lu, Omar Castaneda, Sonja Sorensen, Saad Z. Usmani, Eileen Zhang, Stephen Huo, Sundar Jagannath Tags: 519 Source Type: research
Stem Cell Mobilization Yields with Daratumumab (Dara) and Lenalidomide(Len)-Containing Quadruplet Induction Therapy in Patients with Newly Diagnosed Multiple Myeloma (NDMM): Real World Experience
Quadruplet therapy is gaining momentum as a frontline therapeutic strategy in transplant eligible NDMM patients. Using data from the MASTER and GRIFFIN trials, Chhabra et al. recently reported that Dara-Len containing quadruplet therapies had minimal impact on stem cell harvesting and engraftment. It is unclear if this remains true in a real world setting where heterogeneity exists among patients and in institutional practices. Herein, we describe our experience of stem cell mobilization and collection in NDMM patients receiving DRVd at Levine Cancer Institute (LCI) and Emory Winship Cancer Institute. (Source: Biology of B...
Source: Biology of Blood and Marrow Transplantation - February 1, 2024 Category: Hematology Authors: Cindy Varga, Myra Robinson, Hamid Ehsan, Danielle Roberts, Sara Dicamillo, Vikas Gupta, Shanice Borden, Manisha Bhutani, Barry A. Paul, Shebli Atrash, Christopher Ferreri, Ajay K. Nooka, Peter M. Voorhees, Nisha Joseph Tags: 517 Source Type: research
Efficacy and Safety in Patients with Lenalidomide-Refractory Multiple Myeloma and 1 –3 Prior Lines Who Received a Single Infusion of Ciltacabtagene Autoleucel As Study Treatment in the Phase 3 Cartitude-4 Trial
CARTITUDE-4 (NCT04181827) is a phase 3 trial comparing ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen chimeric antigen receptor-T cell (CAR-T) therapy, with standard of care (SOC; pomalidomide, bortezomib, and dexamethasone [PVd] or daratumumab, pomalidomide, and dexamethasone [DPd]) in patients (pts) with lenalidomide (len)-refractory multiple myeloma (MM). Pts in the cilta-cel arm had significantly improved progression-free survival (PFS), higher rates of ≥complete response (CR), and higher overall response rate (ORR) versus SOC in the intent-to-treat (ITT) set. (Source: Biology of Blood and Marrow Transplantation)
Source: Biology of Blood and Marrow Transplantation - February 1, 2024 Category: Hematology Authors: M Hasib Sidiqi, Paolo Corradini, Duncan Purtill, Hermann Einsele, Binod Dhakal, Lionel Karlin, Salomon Manier, Shinsuke Iida, Sebastian Giebel, Simon J Harrison, Brea Lipe, Dr. Abdullah Mohammad Khan, Jordan M Schecter, Carolyn C Jackson, Tzu-min Yeh, Arn Tags: 514 Source Type: research
Contemporary Treatment Options Beyond Chimeric Antigen Receptor (CAR) T-Cell Therapies for Patients with Relapsed or Refractory Large B-Cell Lymphoma (LBCL): A Systematic Literature Review (SLR)
Refractory or relapsed large B-cell lymphoma (R/R LBCL) remains a significant challenge for patients (Coiffier et al. Blood. 2010). Chimeric antigen receptor (CAR) T-cell therapy has emerged as standard of care for most patients with R/R LBCL after receiving the initial line of treatment (Dreger et al. Blood Adv. 2020). Other therapies with different mechanisms of action also received regulatory approvals as second or third line (2L or 3L) treatment in recent years. We performed an SLR to understand the efficacy and real-world (RW) effectiveness of non –CAR T-cell therapies for R/R LBCL including tafasitamab with lenalid...
Source: Biology of Blood and Marrow Transplantation - February 1, 2024 Category: Hematology Authors: Matthew Lunning, Christopher Dieyi, Polly Field, Zhen-Huan Hu, Marta Radwan, Harry Miao, Fang Sun, Christine Fu, Clare Spooner, Marcelo C. Pasquini Tags: 493 Source Type: research
Discovery of an Inherited Variant Associated with Susceptibility to Secondary Acute Lymphoblastic Leukemia (ALL) after Lenalidomide Maintenance and Autologous HCT for Multiple Myeloma (MM)
An increased risk of ALL second primary malignancy (SPM) has been observed with lenalidomide maintenance therapy after autologous HCT (len-post-autoHCT) for MM. Lenalidomide exerts its therapeutic effects via cereblon-mediated downregulation of the transcription factors Ikaros (IKZF1) and Aiolos (IKZF3). Inherited susceptibility variants in IKZF1 have been described for de novo ALL. We performed a case-control germline targeted sequencing study of the entire IKZF1 and IKZF3 genes with mean coverage ∼2,200X to investigate inherited susceptibility to ALL SPM risk. (Source: Biology of Blood and Marrow Transplantation)
Source: Biology of Blood and Marrow Transplantation - February 1, 2024 Category: Hematology Authors: Qianqian Zhu, Megan Herr, Shuyi Liang, Qiang Hu, Prashant K Singh, Xinyu Gao, Marcelo C. Pasquini, Jessica T. Leonard, Ashley Rosko, Ruthee-Lu Bayer, Amrita Krishnan, Edward A. Stadtmauer, Richard T. Maziarz, Phillip L McCarthy, Theresa E. Hahn Tags: 118 Source Type: research
GSE222727 Proteomic profiling Proteogenomic landscape of multiple myeloma reveals CDK6 upregulation as a targetable resistance mechanism for lenalidomide in multiple myeloma
Contributors : Anna Dolnik ; Evelyn Ramberger ; Jan Kr önkeSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensMultiple myeloma is a plasma cell malignancy of the bone marrow. Despite therapeutic advances in multiple myeloma, it remains incurable and better risk stratification as well as new therapies are therefore highly needed. While genetics and gene expression have been extensively studied leading to new insights in disease biology and improved prognostic models, the proteome of multiple myeloma has not been systematically assessed. Here, we provide a comprehensive multi-omic anal...
Source: GEO: Gene Expression Omnibus - January 31, 2024 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
Determinants of lenalidomide response with or without erythropoiesis-stimulating agents in myelodysplastic syndromes: the HOVON89 trial
Leukemia, Published online: 31 January 2024; doi:10.1038/s41375-024-02161-6Determinants of lenalidomide response with or without erythropoiesis-stimulating agents in myelodysplastic syndromes: the HOVON89 trial (Source: Leukemia)
Source: Leukemia - January 31, 2024 Category: Hematology Authors: A. A. van de Loosdrecht E. M. P. Cremers C. Alhan C. Duetz F. E. M. in ’t Hout H. A. Visser-Wisselaar D. A. Chitu A. Verbrugge S. M. Cunha G. J. Ossenkoppele J. J. W. M. Janssen S. K. Klein E. Vellenga G. A. Huls P. Muus S. M. C. Langemeijer G. E. de Gr Source Type: research
Cereblon-Targeting Ligase Degraders in Myeloma
Cereblon-targeting degraders, including immunomodulatory imide drugs lenalidomide and pomalidomide alongside cereblon E3 ligase modulators like iberdomide and mezigdomide, have demonstrated significant anti-myeloma effects. These drugs play a crucial role in diverse therapeutic approaches for multiple myeloma (MM), emphasizing their therapeutic importance across various disease stages. Despite their evident efficacy, approximately 5% to 10% of MM patients exhibit primary resistance to lenalidomide, and resistance commonly develops over time. Understanding the intricate mechanisms of action and resistance to this drug class...
Source: Hematology/Oncology Clinics of North America - January 31, 2024 Category: Cancer & Oncology Authors: Holly Lee, Paola Neri, Nizar J. Bahlis Source Type: research
Case report: Successful treatment of a patient with relapsed/refractory primary central nervous system lymphoma with thiotepa-based induction, autologous stem cell transplantation and maintenance
Despite significant improvements in prognosis, a subset of patients with primary central nervous system lymphoma (PCNSL) remains at high risk for relapse. The treatment of relapsed and refractory (R/R) PCNSL remains a major clinical challenge. Herein, we present a 24-year-old patient with PCNSL who relapsed 4 years after initial diagnosis and subsequently became refractory to high-dose methotrexate (HD-MTX), temozolomide, whole brain radiation therapy (WBRT), ibrutinib, and lenalidomide. She received thiotepa with anti-programmed cell death protein 1 (PD-1) antibody and achieved partial remission and then underwent autolog...
Source: Frontiers in Oncology - January 29, 2024 Category: Cancer & Oncology Source Type: research
Case report: POEMS syndrome masquerades as diabetic foot
We present the case of a 54-year-old woman with reasonable blood sugar control who presented with a diabetic foot combined with severe peripheral neuropathy and vascular disease. Lower limb muscle weakness, muscle atrophy, skin pigmentation, and emaciation were also observed. Although her muscle strength improved after glucocorticoid treatment, it remained challenging to account for the other symptoms in this particular patient with chronic inflammatory demyelinating polyneuropathy. Plump liver and spleen, hidden bone lesions combined with seemingly unexplained cerebral infarction, and serous effusion led us to suspect pol...
Source: Frontiers in Neurology - January 26, 2024 Category: Neurology Source Type: research
Daratumumab-based immunotherapy vs. lenalidomide, bortezomib and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: a systemic review
ConclusionThis meta-analysis suggests that daratumumab-containing immunotherapy is superior to RVD in the depth of treatment efficacy, progression-free survival, and lower treatment-related discontinuation rates. Limited by the lack of head-to-head clinical trials, this conclusion needs to be verified by concurrent cohort studies. (Source: Frontiers in Oncology)
Source: Frontiers in Oncology - January 25, 2024 Category: Cancer & Oncology Source Type: research
New Therapies on the Horizon for Relapsed Refractory Multiple Myeloma
Hematol Oncol Clin North Am. 2024 Jan 11:S0889-8588(23)00180-6. doi: 10.1016/j.hoc.2023.12.013. Online ahead of print.ABSTRACTDespite improved treatments, most patients with multiple myeloma (MM) will experience relapse. Several novel agents have demonstrated activity and tolerability in early phase clinical trials. Venetoclax is a B-cell lymphoma 2 (Bcl-2) inhibitor with activity in patients with t(11;14) and/or Bcl-2 expression. Iberdomide and mezigdomide are cereblon E3 ligase modulators with higher potency, immunomodulatory, and antiproliferative activity compared with lenalidomide and pomalidomide. They have shown pro...
Source: Clinical Lymphoma and Myeloma - January 12, 2024 Category: Cancer & Oncology Authors: Nadine Abdallah Shaji K Kumar Source Type: research
