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JOURNAL ARTICLE
Aina Oliver-Caldés, Marta Español-Rego, Aintzane Zabaleta, Veronica Gonzalez-Calle, Sergio Navarro-Velázquez, Susana Inoges, Ascensión López-Díaz de Cerio, Valentin Cabañas, Nieves López-Muñoz, Paula Rodriguez-Otero, Juan Luis Reguera-Ortega, David F Moreno, Núria Martínez-Cibrian, Lucía López-Corral, Lorena Pérez-Amill, Beatriz Martin-Antonio, Laura Rosinol, Joan Cid, Natalia Tovar, Joaquin Saez-Peñataro, Miriam Lopez-Parra, Eulalia Olesti, Elena Guillen, Sara Varea, Luis Gerardo Rodríguez-Lobato, Anthony M Battram, Marta-Sonia Gonzalez-Perez, Andres Sanchez-Salinas, Azucena González-Navarro, Valentin Ortiz-Maldonado, Julio Delgado, Felipe Prosper, Manel Juan, Joaquin Martinez-Lopez, Jose M Moraleda, Maria Victoria Mateos, Alvaro Urbano-Ispizua, Bruno Paiva, Mariona Pascal, Carlos Fernández de Larrea
BACKGROUND: BCMA-CARTs improve results obtained with conventional therapy in the treatment of relapsed/refractory multiple myeloma. However, the high demand and expensive costs associated with CART therapy might prove unsustainable for health systems. Academic CARTs could potentially overcome these issues. Moreover, response biomarkers and resistance mechanisms need to be identified and addressed to improve efficacy and patient selection. Here, we present clinical and ancillary results of the 60 patients treated with the academic BCMA-CART, ARI0002h, in the CARTBCMA-HCB-01 trial...
March 11, 2024: Clinical Cancer Research
#2
JOURNAL ARTICLE
Jörn C Albring, Karin Frebel, Anika Wohlgemuth, Christian Schwöppe, Stephan Hailfinger, Georg Lenz, Matthias Stelljes
Antibody-based immunotherapies have revolutionized leukemia and lymphoma treatment, with animal studies being crucial in evaluating effectiveness and side effects. By targeting the evolutionary conserved Slamf7 immune receptor, which is naturally expressed by the murine multiple myeloma cell line MPC-11, we have developed a syngeneic mouse model for direct comparison of three immunotherapies: monoclonal antibodies (mAb), bispecific T cell engagers (BiTE), and CAR T cells (CART), all targeting Slamf7. Slamf7-BiTE is a bispecific single-chain antibody consisting of α-Slamf7 and α-CD3 Fv fragments joined through a Gly-Ser linker, and Slamf7-CART comprises the α-Slamf7 Fv fragment fused to the msCD8α transmembrane and msCD28, 4-1BB and CD3ζ intracellular signaling domains...
January 10, 2024: Blood Advances
#3
REVIEW
Zainul S Hasanali, Beatrice Razzo, Sandra P Susanibar-Adaniya, Alfred L Garfall, Edward A Stadtmauer, Adam D Cohen
Chimeric antigen receptor T cells (CARTs) represent another powerful way to leverage the immune system to fight malignancy. Indeed, in multiple myeloma, the high response rate and duration of response to B cell maturation antigen-targeted therapies in later lines of disease has led to 2 Food and Drug Administration (FDA) drug approvals and opened the door to the development of this drug class. This review aims to provide an update on the 2 FDA-approved products, summarize the data for the most promising next-generation multiple myeloma CARTs, and outline current challenges in the field and potential solutions...
April 2024: Hematology/oncology Clinics of North America
#4
JOURNAL ARTICLE
Sueh-Li Lim, Cameron Wellard, Elizabeth Moore, Simon J Harrison, Quach Hang, Joy Ho, Rajeev Rajagopal, Andrew Spencer
BACKGROUND: There is no currently available standard of care for triple-class exposed, relapsed refractory myeloma (RRMM) patients in Australia. CARTITUDE-1 (CART-1) was a single-arm, phase 1b/2 study of 97 triple-class exposed RRMM patients, who received BCMA-CAR-T cell therapy with ciltacabtagene autocel. Overall response rate (ORR) was 98%. Median progression free survival (PFS) and overall survival (OS) had not been reached at a median follow-up of 28 months. METHODS: We performed a retrospective analysis on a cohort of CART-1 comparable RRMM patients participating in the Australian and New Zealand Myeloma and Related Diseases Registry (MRDR), to compare outcomes in triple-class exposed MM patients treated with currently available therapies, in a real-world context...
December 27, 2023: Internal Medicine Journal
#5
JOURNAL ARTICLE
Umair Munawar, Xiang Zhou, Sabrina Prommersberger, Silvia Nerreter, Cornelia Vogt, Maximilian J Steinhardt, Marietta Truger, Julia Mersi, Eva Teufel, Seungbin Han, Larissa Haertle, Nicole Banholzer, Patrick Eiring, Sophia Danhof, Miguel Angel Navarro-Aguadero, Adrian Fernandez-Martin, Alejandra Ortiz-Ruiz, Santiago Barrio, Miguel Gallardo, Antonio Valeri, Eva Castellano, Peter Raab, Maximilian Rudert, Claudia Haferlach, Markus Sauer, Michael Hudecek, J Martinez-Lopez, Johannes Waldschmidt, Hermann Einsele, Leo Rasche, K Martin Kortüm
The treatment landscape in multiple myeloma (MM) is shifting from genotoxic drugs to immunotherapies. Monoclonal antibodies, immunoconjugates, T-cell engaging antibodies and CART cells have been incorporated into routine treatment algorithms, resulting in improved response rates. Nevertheless, patients continue to relapse and the underlying mechanisms of resistance remain poorly understood. While Impaired death receptor signaling has been reported to mediate resistance to CART in acute lymphoblastic leukemia, this mechanism yet remains to be elucidated in context of novel immunotherapies for MM...
December 21, 2023: Communications Biology
#6
JOURNAL ARTICLE
Zheng Zhang, Caroline Markmann, Ming Yu, Divyansh Agarwal, Susan Rostami, Wei Wang, Chengyang Liu, Huiwu Zhao, Trini Ochoa, Kalpana Parvathaneni, Xiaoming Xu, Eric Li, Vanessa Gonzalez, Roman Khadka, Jennifer Hoffmann, James J Knox, John Scholler, Brooke Marcellus, David Allman, Joseph A Fraietta, Benjamin Samelson-Jones, Michael C Milone, Dimitri Monos, Alfred L Garfall, Ali Naji, Vijay G Bhoj
Pre-existing anti-human leukocyte antigen (HLA) allo-antibodies constitute a major barrier to transplantation. Current desensitization approaches fail due to ineffective depletion of allo-specific memory B cells (Bmems) and long-lived plasma cells (LLPCs). We evaluate the efficacy of chimeric antigen receptor (CAR) T cells targeting CD19 and B cell maturation antigen (BCMA) to eliminate allo-antibodies in a skin pre-sensitized murine model of islet allo-transplantation. We find that treatment of allo-sensitized hosts with CAR T cells targeting Bmems and LLPCs eliminates donor-specific allo-antibodies (DSAs) and mitigates hyperacute rejection of subsequent islet allografts...
December 19, 2023: Cell reports medicine
#7
JOURNAL ARTICLE
Beatrice Razzo, Alfred L Garfall, Adam D Cohen
B-cell maturation antigen (BCMA)-directed therapies, including antibody-drug conjugates, bispecific antibodies (BsAbs), and chimeric antigen receptor T cells (CARTs), have shown remarkable efficacy in patients with late-line myeloma with prior exposure to immunomodulatory agents, proteasome inhibitors, and anti-CD38 antibodies. However, optimal sequencing of these agents remains to be determined, and management of these patients once they relapse has become a new unmet need. Fortunately, there are multiple options with demonstrated activity after anti-BCMA therapy, including a different BCMA-directed therapy, non-BCMA-directed CARTs and BsAbs, novel non-T-cell-engaging drugs, and standard triplet/quadruplet regimens or salvage stem cell transplant...
December 8, 2023: Hematology—the Education Program of the American Society of Hematology
#8
JOURNAL ARTICLE
Rajiv Kumar, Rajan Kapoor, Sanjeevan Sharma, Suman Kumar Pramanik, Uday Yanamandra, Kundan Mishra, Sanjeev Khera, Ajay Sharma, S Das, Tarun Verma, Jasjit Singh, Velu Nair
BACKGROUND: Bone Marrow Transplant (BMT) is a curative form of therapy for many hematological disorders in both the adult and pediatric patients. The availability of BMT in the AFMS at AHRR for the last 02 decades has been a game changer for the patients. METHODS: We reviewed our BMT data since the inception of the program till Feb 2023. RESULTS: Over 700 patients with more than 23 different types of hematological disorders have undergone this procedure 58%% patients underwent an Autologous BMT and 42% an allogenic BMT...
2023: Medical Journal, Armed Forces India
#9
JOURNAL ARTICLE
Francesc Bosch, John Kuruvilla, Theodoros P Vassilakopoulos, Danilo Di Maio, Michael C Wei, Marie-Helene Blanchet Zumofen, Loretta J Nastoupil
BACKGROUND: No established standard of care exists for relapsed/refractory (RR) follicular lymphoma (FL) after ≥2 prior therapies. We conducted indirect treatment comparisons (ITCs) to compare the efficacy and tolerability of mosunetuzumab with those of available treatments used in this setting. METHODS: A systematic literature review (SLR) and subsequent feasibility assessments were conducted to identify the most suitable comparator studies in terms of design, available endpoints and populations...
February 2024: Clinical Lymphoma, Myeloma & Leukemia
#10
REVIEW
Adam F Binder, Christopher J Walker, Tomer M Mark, Muhamed Baljevic
Competent T-cells with sufficient levels of fitness combat cancer formation and progression. In multiple myeloma (MM), T-cell exhaustion is caused by several factors including tumor burden, constant immune activation due to chronic disease, age, nutritional status, and certain MM treatments such as alkylating agents and proteasome inhibitors. Many currently used therapies, including bispecific T-cell engagers, anti-CD38 antibodies, proteasome inhibitors, and CART-cells, directly or indirectly depend on the anti-cancer activity of T-cells...
2023: Frontiers in Immunology
#11
JOURNAL ARTICLE
Irene Zamanillo, Lucia Medina de Alba, Rodrigo Gil, Rosalia de la Puerta, Rafael Alonso, Ana Jimenez-Ubieto, Maria Teresa Cedena, Maria Calbacho, Rosa Ayala, Joaquin Martinez-Lopez
Anti-CD38 monoclonal antibody (MoAB) therapy has significantly improved the prognosis of patients with multiple myeloma. However, not all patients sustain durable responses. We aimed to describe the natural history of patients relapsed or refractory (R/R) to CD38 MoAB therapy. We performed a single-center, retrospective analysis of the clinical characteristics and outcomes of 81 patients with multiple myeloma who progressed after treatment with daratumumab. Our cohort was heavily pretreated, with a median of two lines prior to daratumumab and only 17 patients received daratumumab as a first line...
August 31, 2023: Life
#12
JOURNAL ARTICLE
Taku Kikuchi, Nobuhiro Tsukada, Kodai Kunisada, Moe Nomura-Yogo, Yuki Oda, Kota Sato, Tomomi Takei, Mizuki Ogura, Yu Abe, Kenshi Suzuki, Tadao Ishida
Bortezomib (Velcade), thalidomide, dexamethasone, platinum (cisplatin), adriamycin (doxorubicin), cyclophosphamide, and etoposide (VTD-PACE) are commonly used as salvage treatment for patients with relapsed/refractory multiple myeloma (RRMM). However, its outcomes in the era of monoclonal antibodies remain unclear. Therefore, this retrospective cohort study assessed the clinical outcomes of 60 patients with RRMM (median four prior treatment lines) administered VTD-PACE. The median follow-up period was 11.1 months, during which they received a median of two cycles of VTD-PACE...
December 2023: Annals of Hematology
#13
JOURNAL ARTICLE
María José Mela Osorio, Carolina Pavlovsky, Miguel Arturo Pavlovsky
Health equity is today an important objective to evenly reach the population among different health care systems. This article will focus on diagnosis and treatment access inequalities in Argentina. Although different aspects must be optimized to overcome access barriers worldwide, access inequalities in some regions of Argentina may depend basically on the type of health coverage or insurance. Health care in Argentina is divided into Public, Social security and Private care systems. Access to diagnosis and disease monitoring will vary according whether the patient is under each of these systems...
July 15, 2023: Seminars in Hematology
#14
REVIEW
Supreet Kaur, Sudarsan Kollimuttathuillam
Plasmablastic Lymphoma is a rare large B-cell lymphoma with unique immunohistochemical and morphological features. It was most commonly associated with HIV infection; however, it's now seen in other immunosuppressed states like autoimmune conditions, post-transplant settings, and even in elderly immunocompetent individuals. Although rare, it is an aggressive lymphoma with unfavorable outcomes. The aim of this manuscript is to have an in-depth review of the current knowledge of epidemiology, pathophysiology, prognostic markers, and treatment approaches currently in use and in clinical trials for this challenging disease...
June 14, 2023: Clinical Lymphoma, Myeloma & Leukemia
#15
JOURNAL ARTICLE
Vladimir Vainstein, Batia Avni, Sigal Grisariu, Shlomit Kfir-Erenfeld, Nathalie Asherie, Boaz Nachmias, Shlomtzion Auman, Revital Saban, Eran Zimran, Miri Assayag, Kalman Filanovsky, Netanel A Horowitz, Eyal Lebel, Adir Shaulov, Michal Gur, Chaggai Rosenbluh, Svetlana Krichevsky, Polina Stepensky, Moshe E Gatt
Multiple myeloma (MM) is characterized by recurrent relapses. Consequently, patients receive multiple therapy lines, including alkylating agents and immune modulators, which have been associated with secondary malignancies such as myelodysplastic syndrome (MDS). Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T cell (CART) therapy is efficacious in patients with relapsed/refractory (R/R) MM. However, the long-term complications, particularly MDS, are not well understood. Whether CART therapy causes or promotes MDS has not been thoroughly investigated...
July 3, 2023: Cancers
#16
JOURNAL ARTICLE
Ruchi Yadav, Lishi Sun, Akhtar Cheema, Vivek Yadav, Jen Chin Wang
Nodular amyloidoma in the lungs is a rare entity, also the occurrence of extramedullary plasmacytoma (EMP) in the lungs is rare. To have concomitant EMP and amyloidoma presented as a single lung mass is even rarer. There was only one similar case reported in the abstract form previously. Our case did not respond to many novel chemotherapy agents, suggesting that this combination of amyloidoma and plasmacytoma belonged to a poor prognosis entity, requiring different treatment modalities, such as early bone marrow transplantation or CART (chimeric antigen receptors T) therapy...
2023: Journal of Investigative Medicine High Impact Case Reports
#17
JOURNAL ARTICLE
Tina Glisovic-Aplenc, Caroline Diorio, John A Chukinas, Kimberly Veliz, Olga Shestova, Feng Shen, Selene Nunez-Cruz, Tiffaney L Vincent, Fei Miao, Michael C Milone, Carl H June, David T Teachey, Sarah K Tasian, Richard Aplenc, Saar Gill
Many hematologic malignancies are not curable with chemotherapy and require novel therapeutic approaches. Chimeric antigen receptor (CAR) T-cell therapy is 1 such approach that involves the transfer of T cells engineered to express CARs for a specific cell-surface antigen. CD38 is a validated tumor antigen in multiple myeloma (MM) and T-cell acute lymphoblastic leukemia (T-ALL) and is also overexpressed in acute myeloid leukemia (AML). Here, we developed human CD38-redirected T cells (CART-38) as a unified approach to treat 3 different hematologic malignancies that occur across the pediatric-to-adult age spectrum...
August 22, 2023: Blood Advances
#18
REVIEW
Vincenzo Sammartano, Marta Franceschini, Sara Fredducci, Federico Caroni, Sara Ciofini, Paola Pacelli, Monica Bocchia, Alessandro Gozzetti
Recent advances in multiple myeloma therapy have increased the depth of response and ultimately survivals; however, the prognosis remains poor. The BCMA antigen is highly expressed in myeloma cells, thus representing a target for novel therapies. Several agents that target BCMA through different mechanisms, including bispecific T cell engagers drug conjugated to antibody and CAR-T cells, are now available or under development. Immunotherapies targeting BCMA have shown good results in efficacy and safety in multiple myeloma patients previously treated with several lines of therapy...
2023: Cancer Drug Resistance
#19
JOURNAL ARTICLE
Christof Scheid
Current approved immunotherapeutic agents such as CART cells are limited to patients with at least 3 or even 4 prior lines of treatment. However more and more patients become refractory to standard regimens in earlier lines. Mohyuddin et al. examined the inclusion criteria of current immunotherapeutic trials in myeloma and propose a change to put more emphasis on refractoriness to 3 or more agents and to omit a required number of lines of therapy in current and future protocols. Commentary on: Mohyuddin et al...
April 11, 2023: British Journal of Haematology
#20
JOURNAL ARTICLE
Radhika Bansal, Mizba Baksh, Jeremy T Larsen, Matthew A Hathcock, David Dingli, A Keith Stewart, Prashant Kapoor, Taxiarchis Kourelis, Suzanne R Hayman, Rahma M Warsame, Rafael Fonseca, P Leif Bergsagel, Sikander Ailawadhi, Shaji K Kumar, Yi Lin
Bone marrow (BM) assessment of minimal residual disease (MRD) is prognostic for survival in multiple myeloma (MM). BM is still hypocellular at month 1 post CAR-T, thus the value of MRD negative (MRDneg) status at this timepoint is unclear. We examined the impact of month 1 BM MRD status in MM patients who received CART at Mayo Clinic between 8/2016 and 6/2021. Among 60 patients, 78% were BM-MRDneg at month 1; and 85% (40/47) of these patients also had decreased to less than normal level of both involved and uninvolved free light chain (FLC < NL)...
April 5, 2023: Blood Cancer Journal
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