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41 results on '"Zimran, Eran"'

1. Clinical evaluation and determinants of response to HBI0101 (BCMA CART) therapy in relapsed/refractory multiple myeloma

Author

Kfir-Erenfeld, Shlomit, Asherie, Nathalie, Lebel, Eyal, Vainstein, Vladimir, Assayag, Miri, Dubnikov Sharon, Tatyana, Grisariu, Sigal, Avni, Batia, Elias, Shlomo, Alexander-Shani, Rivka, Bessig, Nomi, Shehadeh, Alaa, Ishtay, Aseel, Zelmanovich, Veronica, Zimran, Eran, Pick, Marjorie, Roziner, Ilan, Kenett, Ron S., Cohen, Yael, Avivi, Irit, Cohen, Cyrille J., Gatt, Moshe E., and Stepensky, Polina

Published
2024
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4. Dysregulated iron metabolism in polycythemia vera: etiology and consequences.

Author

Ginzburg, Yelena, Feola, Maria, Zimran, Eran, Varkonyi, Judit, Ganz, Tomas, and Hoffman, Ronald

Subjects
Anemia, Iron-Deficiency, Animals, Humans, Iron, Myeloproliferative Disorders, Polycythemia Vera, Signal Transduction, Thrombosis
Abstract

Polycythemia vera (PV) is a chronic myeloproliferative neoplasm. Virtually all PV patients are iron deficient at presentation and/or during the course of their disease. The co-existence of iron deficiency and polycythemia presents a physiological disconnect. Hepcidin, the master regulator of iron metabolism, is regulated by circulating iron levels, erythroblast secretion of erythroferrone, and inflammation. Both decreased circulating iron and increased erythroferrone levels, which occur as a consequence of erythroid hyperplasia in PV, are anticipated to suppress hepcidin and enable recovery from iron deficiency. Inflammation which accompanies PV is likely to counteract hepcidin suppression, but the relatively low serum ferritin levels observed suggest that inflammation is not a major contributor to the dysregulated iron metabolism. Furthermore, potential defects in iron absorption, aberrant hypoxia sensing and signaling, and frequency of bleeding to account for iron deficiency in PV patients have not been fully elucidated. Insufficiently suppressed hepcidin given the degree of iron deficiency in PV patients strongly suggests that disordered iron metabolism is an important component of the pathobiology of PV. Normalization of hematocrit levels using therapeutic phlebotomy is the most common approach for reducing the incidence of thrombotic complications, a therapy which exacerbates iron deficiency, contributing to a variety of non-hematological symptoms. The use of cytoreductive therapy in high-risk PV patients frequently works more effectively to reverse PV-associated symptoms in iron-deficient relative to iron-replete patients. Lastly, differences in iron-related parameters between PV patients and mice with JAK2 V617F and JAK2 exon 12 mutations suggest that specific regions in JAK2 may influence iron metabolism by nuanced changes of erythropoietin receptor signaling. In this review, we comprehensively discuss the clinical consequences of iron deficiency in PV, provide a framework for understanding the potential dysregulation of iron metabolism, and present a rationale for additional therapeutic options for iron-deficient PV patients.

Published
2018

7. OA-34 Feasibility of a novel academic anti-BCMA chimeric antigen receptor T-cell (CART) (HBI0101) for the treatment of relapsed and refractory AL amyloidosis

Author

Lebel, Eyal, primary, Kfir-erenfeld, Shlomit, additional, Asherie, Nathalie, additional, Grisariu, Sigal, additional, Avni, Batia, additional, Elias, Shlomo, additional, Assayag, Miri, additional, Dubnikov, Tatyana, additional, Zalcman, Nomi, additional, Pick, Marjorie, additional, Zimran, Eran, additional, Shaulov, Adir, additional, Cohen, Yaël, additional, Avivi, Irit, additional, Cohen, Cyrille, additional, Stepensky, Polina, additional, and Gatt, Moshe, additional

Published
2023
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8. P-026 Safety and efficacy of a locally produced novel anti-BCMA chimeric antigen receptor T-cell (CART) (HBI0101) for the treatment of relapsed and refractory multiple myeloma

Author

Lebel, Eyal, primary, Kfir-erenfeld, Shlomit, additional, Asherie, Nathalie, additional, Grisariu, Sigal, additional, Avni, Batia, additional, Elias, Shlomo, additional, Assayag, Miri, additional, Dubnikov, Tatyana, additional, Zalcman, Nomi, additional, Pick, Marjorie, additional, Zimran, Eran, additional, Shaulov, Adir, additional, Cohen, Yaël, additional, Avivi, Irit, additional, Cohen, Cyrille, additional, Stepensky, Polina, additional, and Gatt, Moshe, additional

Published
2023
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9. High rate of adenovirus detection in gastrointestinal biopsies of symptomatic stem cell transplant recipients

Author

Pikkel‐Geva, Hagar Z., primary, Grisariu, Sigal, additional, Rivkin, Mila, additional, Stepensky, Polina, additional, Strahilevitz, Jacob, additional, Averbuch, Dina, additional, Orit, Caplan, additional, Even‐Or, Ehud, additional, Zaidman, Irina, additional, Zimran, Eran, additional, Wolf, Dana G., additional, and Avni, Batia, additional

Published
2023
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10. Clonal Myeloid Dysplasia Following CAR T-Cell Therapy: Chicken or the Egg?

Author

Vainstein, Vladimir, primary, Avni, Batia, additional, Grisariu, Sigal, additional, Kfir-Erenfeld, Shlomit, additional, Asherie, Nathalie, additional, Nachmias, Boaz, additional, Auman, Shlomtzion, additional, Saban, Revital, additional, Zimran, Eran, additional, Assayag, Miri, additional, Filanovsky, Kalman, additional, Horowitz, Netanel A., additional, Lebel, Eyal, additional, Shaulov, Adir, additional, Gur, Michal, additional, Rosenbluh, Chaggai, additional, Krichevsky, Svetlana, additional, Stepensky, Polina, additional, and Gatt, Moshe E., additional

Published
2023
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11. Novel strategies for the treatment of myelofibrosis driven by recent advances in understanding the role of the microenvironment in its etiology [version 1; peer review: 3 approved]

Author

Zimran Eran, Maria Zingariello, Maria Teresa Bochicchio, Claudio Bardelli, and Anna Rita Migliaccio

Subjects
Review, Articles, Myelofibrosis, p53, transforming growth factor beta, combination therapy, MDM2 inhibitors, transforming growth factor beta inhibitors, animal models, pre-clinical studies
Abstract

Myelofibrosis is the advanced stage of the Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), characterized by systemic inflammation, hematopoietic failure in the bone marrow, and development of extramedullary hematopoiesis, mainly in the spleen. The only potentially curative therapy for this disease is hematopoietic stem cell transplantation, an option that may be offered only to those patients with a compatible donor and with an age and functional status that may face its toxicity. By contrast, with the Philadelphia-positive MPNs that can be dramatically modified by inhibitors of the novel BCR-ABL fusion-protein generated by its genetic lesion, the identification of the molecular lesions that lead to the development of myelofibrosis has not yet translated into a treatment that can modify the natural history of the disease. Therefore, the cure of myelofibrosis remains an unmet clinical need. However, the excitement raised by the discovery of the genetic lesions has inspired additional studies aimed at elucidating the mechanisms driving these neoplasms towards their final stage. These studies have generated the feeling that the cure of myelofibrosis will require targeting both the malignant stem cell clone and its supportive microenvironment. We will summarize here some of the biochemical alterations recently identified in MPNs and the novel therapeutic approaches currently under investigation inspired by these discoveries.

Published
2019
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14. Letermovir Prophylaxis for High-Risk Allogenic Transplantation Recipients, Real- World Israeli Experience

Author

Grisariu Greenzaid, Sigal, primary, Ram, Ron, additional, Kazuli, Mona, additional, Yehudai-Ofir, Dana, additional, Shargian, Liat, additional, Zuckerman, Tsila, additional, Yeshurun, Moshe, additional, Amit, Odelia, additional, Bar-On, Yael, additional, Zimran, Eran, additional, Shaulov, Adir, additional, Stepensky, Polina, additional, Strahilevitz, Jacob, additional, and Avni, Batia, additional

Published
2022
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15. Risk factors and outcomes of COVID‐19 in adult patients with hematological malignancies: A single‐center study showing lower than expected rates of hospitalization and mortality.

Author

Aumann, Shlomzion, Tsubary, Uria, Nachmias, Boaz, Ben Yehuda, Dina, Lavie, David, Goldschmidt, Neta, Vainstein, Vladimir, Libster, Diana, Saban, Revital, Shaulov, Adir, Israel, Sarah, Avni, Batia, Grisariu, Sigal, Bdolah‐Amram, Tali, Gatt, Moshe, and Zimran, Eran

Subjects
HEMATOLOGIC malignancies, COVID-19, DEATH rate, MONOCLONAL antibodies, HOSPITAL patients
Abstract

Background: Studies addressing coronavirus disease 2019 (COVID‐19) in patients with hematological malignancies have reported mortality rates of up to 40%; however, included predominantly hospitalized patients. Methods: During the first year of the pandemic, we followed adult patients with hematological malignancies treated at a tertiary center in Jerusalem, Israel, who contracted COVID‐19, with the aim of studying risk factors for adverse COVID‐19‐related outcomes. We used remote communication to track patients managed at home‐isolation, and patient questioning to assess the source of COVID‐19 infection, community versus nosocomial. Results: Our series included 183 patients, median age was 62.5 years, 72% had at least one comorbidity and 39% were receiving active antineoplastic treatment. Hospitalization, critical COVID‐19, and mortality rates were 32%, 12.6%, and 9.8%, respectively, remarkably lower than previously reported. Age, multiple comorbidities, and active antineoplastic treatment were significantly associated with hospitalization due to COVID‐19. Treatment with monoclonal antibodies was strongly associated with both hospitalization and critical COVID‐19. In older (≥60) patients not receiving active antineoplastic treatment, mortality, and severe COVID‐19 rates were comparable to those of the general Israeli population. We did not detect patients that contracted COVID‐19 within the Hematology Division. Conclusion: These findings are relevant for the future management of patients with hematological malignancies in COVID‐19‐affected regions. [ABSTRACT FROM AUTHOR]

Published
2023
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16. Development and manufacturing of novel locally produced anti-BCMA CART cells for the treatment of relapsed/refractory multiple myeloma: phase I clinical results

Author

Asherie, Nathalie, primary, Kfir-Erenfeld, Shlomit, additional, Avni, Batia, additional, Assayag, Miri, additional, Dubnikov, Tatyana, additional, Zalcman, Nomi, additional, Lebel, Eyal, additional, Zimran, Eran, additional, Shaulov, Adir, additional, Pick, Marjorie, additional, Cohen, Yael, additional, Avivi, Irit, additional, Cohen, Cyrille, additional, Gatt, Moshe E., additional, Grisariu, Sigal, additional, and Stepensky, Polina, additional

Published
2022
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17. Feasibility of a Novel Academic BCMA-CART (HBI0101) for the Treatment of Relapsed and Refractory AL Amyloidosis

Author

Kfir-Erenfeld, Shlomit, primary, Asherie, Nathalie, additional, Grisariu, Sigal, additional, Avni, Batia, additional, Zimran, Eran, additional, Assayag, Miri, additional, Sharon, Tatyana Dubnikov, additional, Pick, Marjorie, additional, Lebel, Eyal, additional, Shaulov, Adir, additional, Cohen, Yael C., additional, Avivi, Irit, additional, Cohen, Cyrille J., additional, Stepensky, Polina, additional, and Gatt, Moshe E., additional

Published
2022
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19. Rituximab, methotrexate, procarbazine and lomustine (R-MPL) for the treatment of primary Central nervous system lymphoma

Author

Lebel, Eyal, primary, Goldschmidt, Neta, additional, Siegal, Tali, additional, Lossos, Alexander, additional, Rosenberg, Shai, additional, Makranz, Chen, additional, Linetski, Eduard, additional, Gatt, Moshe E., additional, Gural, Alexander, additional, Saban, Revital, additional, Lavie, David, additional, Vainstein, Vladimir, additional, Zimran, Eran, additional, Avni, Batia, additional, Grisaro, Sigal, additional, Shaulov, Adir, additional, and Nachmias, Boaz, additional

Published
2022
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21. COVID-19 Among Patients with Hematological Malignancies: Experience from a Tertiary Center Showing Lower Than Expected Mortality and Establishing the Safety of in-Hospital Patient Care during the Pandemic

Author

Aumann, Shlomzion, primary, Tsubary, Uria, additional, Israel, Sarah, additional, Ben Yehuda, Dina, additional, Lavie, David, additional, Goldschmidt, Neta, additional, Vainstein, Vladimir, additional, Libster, Diana, additional, Saban, Revital, additional, Shaulov, Adir, additional, Avni, Batia, additional, Nachmias, Boaz, additional, Grisariu, Sigal, additional, Paltiel, Ora, additional, Gatt, Moshe, additional, and Zimran, Eran, additional

Published
2021
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22. COVID-19 among patients with hematological malignancies: a national Israeli retrospective analysis with special emphasis on treatment and outcome

Author

Levy, Ilana, primary, Lavi, Avital, additional, Zimran, Eran, additional, Grisariu, Sigal, additional, Aumann, Shlomzion, additional, Itchaki, Gilad, additional, Berger, Tamar, additional, Raanani, Pia, additional, Harel, Reut, additional, Aviv, Ariel, additional, Lavi, Noa, additional, Zuckerman, Tsila, additional, Shvidel, Lev, additional, Jarchowsky, Osnat, additional, Ellis, Martin, additional, Herzog Tzarfati, Katrin, additional, Koren-Michowitz, Maya, additional, Sherf, Yehonatan, additional, Levi, Itai, additional, Sofer, Orit, additional, Shpilberg, Ofer, additional, Dally, Nagib, additional, Suriu, Celia, additional, Braester, Andrei, additional, Ben Barouch, Sharon, additional, Leiba, Merav, additional, Goldstein, Daniela, additional, Sarid, Nadav, additional, Yeganeh, Shay, additional, Halloun, Jabour, additional, Mittelman, Moshe, additional, and Tadmor, Tamar, additional

Published
2021
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23. Neutrophil decline rate following autologous transplant for lymphoma is a predictor of patients' outcome.

Author

Lebel, Eyal, Vainstein, Vladimir, Ashkenazi, Maayan, Zimran, Eran, Stepensky, Polina, Grisariu, Sigal, and Avni, Batia

Subjects
AUTOGRAFTS, NEUTROPHILS, LYMPHOMAS, NEUTROPENIA, OVERALL survival
Abstract

Neutropenia postchemotherapy is associated with favorable outcomes, which was attributed to optimal dosing. However, little is known about the neutrophil decline rate as a predictor of cancer outcomes, which may reflect a dynamic marker of chemosensitivity. We assessed the association between the neutrophil decline rate and disease outcomes in a known cohort of 212 lymphoma patients, treated with thiotepa, etoposide, cyclophosphamide, cytarabine, and melphalan (TECAM) conditioning followed by autologous transplant in our center between 2000 and 2013. Slower neutrophil decline rate was correlated with worse overall survival, mediated not by shorter time to progression (TTP), but rather by worse survival post-progression, possibly pointing to chemosensitivity at each line of therapy as the responsible mechanism. The effect was seen across histologies and was independent of stronger predictors of outcome like performance status (PS) and response before transplant. Prospective research is needed to confirm our results and expand their validity to other clinical scenarios. [ABSTRACT FROM AUTHOR]

Published
2022
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26. Novel strategies for the treatment of myelofibrosis driven by recent advances in understanding the role of the microenvironment in its etiology

Author

Anna Rita Migliaccio, Claudio Bardelli, Maria Teresa Bochicchio, Maria Zingariello, Zimran Eran, Eran Z., Zingariello M., Bochicchio M.T., Bardelli C., and FRANCO MIGLIACCIO ANNA RITA

Subjects
0301 basic medicine, medicine.medical_treatment, Fusion Proteins, bcr-abl, Myelofibrosis, Review, Disease, Hematopoietic stem cell transplantation, Bioinformatics, Primary Myelofibrosi, 0302 clinical medicine, Bone Marrow, Tumor Microenvironment, Medicine, pre-clinical studies, General Pharmacology, Toxicology and Pharmaceutics, Transforming growth factor beta inhibitor, Hematopoietic Stem Cell Transplantation, Myelofibrosi, Articles, General Medicine, animal models, 3. Good health, Extramedullary hematopoiesis, medicine.anatomical_structure, MDM2 inhibitor, Hematopoiesis, Extramedullary, 030220 oncology & carcinogenesis, Stem cell, Pre-clinical studie, Human, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Myeloproliferative Disorders, Humans, Animal model, transforming growth factor beta inhibitors, Combination therapy, Myeloproliferative Disorder, P53, Tumor microenvironment, General Immunology and Microbiology, business.industry, medicine.disease, 030104 developmental biology, Primary Myelofibrosis, MDM2 inhibitors, Transforming growth factor beta, Bone marrow, business
Abstract

Myelofibrosis is the advanced stage of the Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), characterized by systemic inflammation, hematopoietic failure in the bone marrow, and development of extramedullary hematopoiesis, mainly in the spleen. The only potentially curative therapy for this disease is hematopoietic stem cell transplantation, an option that may be offered only to those patients with a compatible donor and with an age and functional status that may face its toxicity. By contrast, with the Philadelphia-positive MPNs that can be dramatically modified by inhibitors of the novel BCR-ABL fusion-protein generated by its genetic lesion, the identification of the molecular lesions that lead to the development of myelofibrosis has not yet translated into a treatment that can modify the natural history of the disease. Therefore, the cure of myelofibrosis remains an unmet clinical need. However, the excitement raised by the discovery of the genetic lesions has inspired additional studies aimed at elucidating the mechanisms driving these neoplasms towards their final stage. These studies have generated the feeling that the cure of myelofibrosis will require targeting both the malignant stem cell clone and its supportive microenvironment. We will summarize here some of the biochemical alterations recently identified in MPNs and the novel therapeutic approaches currently under investigation inspired by these discoveries.

Published
2019

29. Feasibility of a Novel Academic Anti-BCMA Chimeric Antigen Receptor T-Cell (CART) (HBI0101) for the Treatment of Relapsed and Refractory AL Amyloidosis

Author

Lebel, Eyal, Kfir-Erenfeld, Shlomit, Asherie, Nathalie, Grisariu, Sigal, Avni, Batia, Elias, Shlomo, Assayag, Miri, Dubnikov, Tatyana, Zalcman, Nomi, Pick, Marjorie, Zimran, Eran, Cohen, Yael C., Avivi Mazza, Irit, Cohen, Cyrille, Stepensky, Polina, and Gatt, Moshe E

Abstract

BACKGROUND:While anti-BCMA chimeric antigen receptor T-cell therapy (CART) have proven safe and efficient in multiple myeloma (MM), its application to AL amyloidosis (AL), has been restricted due to the frailty of this population and rarity of disease. HBI0101 therapy is a novel anti-BCMA CART-based therapy developed at Hadassah Medical Center and Bar-Ilan University for MM treatment. In a phase Ia-b/2 study (NCT04720313), HBI0101 has demonstrated manageable safety with therapeutic efficacy in over 70 MM patients. Although BCMA targeting in AL has been questioned because of relatively low expression of this antigen on AL plasma cells (PC), we have previously reported that this level of expression is sufficient to enable PC eradication by HBI0101 CART ex vivo. Based on this observation, we have treated 9 AL patients in our study, which represent the largest cohort of AL treated with anti-BCMA CART reported so far.

Published
2023
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30. Safety and Efficacy of a Locally Produced Novel Anti-BCMA Chimeric Antigen Receptor T-Cell (CART) (HBI0101) for the Treatment of Relapsed and Refractory Multiple Myeloma

Author

Lebel, Eyal, Asherie, Nathalie, Kfir-Erenfeld, Shlomit, Avni, Batia, Grisariu, Sigal, Elias, Shlomo, Assayag, Miri, Dubnikov, Tatyana, Zalcman, Nomi, Pick, Marjorie, Zimran, Eran, Cohen, Yael C., Avivi Mazza, Irit, Cohen, Cyrille, Gatt, Moshe E, and Stepensky, Polina

Abstract

BACKGROUND:Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CART) therapy shows remarkable efficacy in patients with relapsed and/or refractory (R/R) multiple myeloma (MM), with recent phase 3 studies showing clear advantage of idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel)over standard-of-care. However, access to these commercial CART products is a major barrier, and it is estimated that only around a quarter of eligible R/R MM patients will receive CART nowadays.

Published
2023
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31. The Utility of a Coagulation Laboratory Profile in Addition to Clinical Risk Factors for Thrombosis Risk Evaluation in Patients with Myeloproliferative Neoplasms: A Pilot Study

Author

Shapira, Inbal, Shai, Ela, Kalish, Yossef, Tsubary, Uria, Aumann, Shlomzion, Arad, Ariela, Roth Jelinek, Batia, Buchman, Noa, Gatt, Moshe E, and Zimran, Eran

Abstract

Background:Patients (pts) with myeloproliferative neoplasms (MPN) have a significantly increased risk of arterial and venous thrombotic events (TEs), while some pts may paradoxically suffer from bleeding manifestations. Thrombosis risk evaluation in polycythemia vera (PV) and essential thrombocythemia (ET) has important implications for patient management, however, the currently used risk stratification models are extremely limited.

Published
2023
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37. Paradoxical response in ocular bartonellosis

Author

Zimran, Eran, primary, Shilo, Smadar, additional, Florescu, Tatiana, additional, Dotan, Shlomo, additional, Balag, Shay, additional, Mevorach, Dror, additional, Shibolet, Oren, additional, and Amer, Radgonde, additional

Published
2011
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38. Downregulation of KLF6 is an early event in hepatocarcinogenesis, and stimulates proliferation while reducing differentiation

Author

Kremer-Tal, Sigal, primary, Narla, Goutham, additional, Chen, Yingbei, additional, Hod, Eldad, additional, DiFeo, Analisa, additional, Yea, Steven, additional, Lee, Ju-Seog, additional, Schwartz, Myron, additional, Thung, Swan N., additional, Fiel, Isabel M., additional, Banck, Michaela, additional, Zimran, Eran, additional, Thorgeirsson, Snorri S., additional, Mazzaferro, Vincenzo, additional, Bruix, Jordi, additional, Martignetti, John A., additional, Llovet, Josep M., additional, and Friedman, Scott L., additional

Published
2007
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40. Valproic Acid Expands the Numbers of HSCs from Cord Blood CD34+Cells By Linking Epigenetic Modifications to Mitochondrial Remodeling and p53 Upregulation

Author

Papa, Luena, Zimran, Eran, Djedaini, Mansour, and Hoffman, Ronald

Abstract

Umbical cord blood (UCB) is an important source of hematopoietic stem cells (HSCs) for allogeneic transplantation of patients suffering from hematological malignancies and genetic disorders. Its use, however, as an HSC graft for adults has been restricted due to the limited numbers of HSCs within a single UCB unit. We have previously reported that UCB CD34+cell numbers can be expanded over a seven-day period of incubation by ex vivotreatment with a cytokine combination and the histone deacetylase inhibitor, valproic acid (VPA) (Chaurasia et al. J Clin Invest. 2014:124(6): 2378-2395). In this study, we addressed the mechanism underling this ex-vivoexpansion of UCB-derived CD34+cells. We found that VPA triggered two distinct phases of HSC behavior. The first phase (days 1-4) was characterized by a prompt elevation of the expression of stem cell phenotypic markers (CD90 and CD49f), which was associated with acetylation of histone H3, and expression of pluripotency genes including OCT4, NANOG, and SOX2. During this period, the cells underwent a limited number of cell divisions. The second phase (days 4-7) was characterized by a greater number of cell divisions that resulted in a drastic increase in the absolute number of phenotypically defined HSCs. Both acetylation of H3 and expression of the pluripotency genes were transient events since they were no longer evident during the second phase. During the entire incubation period, VPA-induced HSC cells maintained a distinct mitochondrial metabolic profile characterized by low mitochondrial potential, ROS levels and mass. Remarkably, the p38 activity, a downstream target of ROS, was also suppressed in VPA-expanded HSCs. Given that both ROS and p38 activity lead to exhaustion and limit the lifespan of the pool of HSCs, our findings suggest that the VPA-expanded HSCs are equipped with mechanisms that monitor and ensure their fitness.In addition, removal of VPA from the culture after 24, 48 and 72hrs of incubation reversed the acetylation of H3 and the expression of the pluripotency genes. These events were further accompanied by the rapid loss of stem cell marker expression (24hrs after removal) leading to decreased HSC numbers. Importantly, upon VPA removal, the expanded cells exhibited an increase in mitochondrial ROS, mass and potential suggesting that the epigenetic reprograming and mitochondrial remodeling triggered by VPA were linked and were both reversible events.

Published
2016
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41. Development and manufacture of novel locally produced anti-BCMA CAR T cells for the treatment of relapsed/refractory multiple myeloma: results from a phase I clinical trial.

Author

Asherie N, Kfir-Erenfeld S, Avni B, Assayag M, Dubnikov T, Zalcman N, Lebel E, Zimran E, Shaulov A, Pick M, Cohen Y, Avivi I, Cohen C, Gatt ME, Grisariu S, and Stepensky P

Subjects
Humans, Immunotherapy, Adoptive adverse effects, Immunotherapy, Adoptive methods, T-Lymphocytes, Antibodies, Multiple Myeloma drug therapy, Receptors, Chimeric Antigen
Abstract

Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR T) therapy shows remarkable efficacy in patients with relapsed and/or refractory (R/R) multiple myeloma (MM). HBI0101, a novel second generation optimized anti- BCMA CAR T-cell therapy, was developed in an academic setting. We conducted a phase I dose-escalation study of HBI0101 (cohort 1: 150x106 CAR T cells, n=6; cohort 2: 450x106 CAR T cells, n=7; cohort 3: 800x106 CAR T cells, n=7) in 20 heavily pre-treated R/R MM patients. Grade 1-2 cytokine release syndrome (CRS) was reported in 18 patients (90%). Neither grade 3-4 CRS nor neurotoxicity of any grade were observed. No dose-limiting toxicities were observed in any cohort. The overall response rate (ORR), (stringent) complete response (CR/sCR), and very good partial response rates were 75%, 50%, and 25%, respectively. Response rates were dose-dependent with 85% ORR, 71% CR, and 57% minimal residual disease negativity in the high-dose cohort 3. Across all cohorts, the median overall survival (OS) was 308 days (range 25-466+), with an estimated OS of 55% as of June 27th (data cut-off). The median progression-free survival was 160 days, with 6 subjects remaining progression free at the time of data cut-off. Our findings demonstrate the manageable safety profile and efficacy of HBI0101. These encouraging data support the decentralization of CAR T production in an academic setting, ensuring sufficient CAR T supply to satisfy the increasing local demand. Clinicaltrials.gov NCT04720313.

Published
2023
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