Review
Oncology
Jason H. Kurzer, Olga K. Weinberg
Summary: PHF6, an epigenetic regulator, acts as a tumor suppressor protein and is commonly associated with T-lymphoblastic leukemia, playing a critical role in lineage plasticity and disease progression within hematopoietic malignancies.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Adam S. Chervin, Jennifer D. Stone, Iwona Konieczna, Kelly M. Calabrese, Ningyan Wang, Dipica Haribhai, Feng Dong, Michael K. White, Luis E. Rodriguez, Gail T. Bukofzer, Paul A. Ellis, Cormac Cosgrove, Claudie Hecquet, Jerry D. Clarin, Joann P. Palma, Edward B. Reilly
Summary: CD3 bispecific T-cell engagers (TCE) are effective in redirecting T cell-mediated killing of tumor cells by bridging target-positive tumors and CD3-expressing effector T cells. ABBV-184, a novel TCR/anti-CD3 bispecific, demonstrates sensitive recognition of low-density peptide/MHC targets and shows potential as a treatment for AML and NSCLC.
MOLECULAR CANCER THERAPEUTICS
(2023)
Article
Health Care Sciences & Services
Larry W. Buie
Summary: CAR T-cell therapy shows significant efficacy in treating hematologic malignancies, but faces limitations such as toxicities, manufacturing challenges, high costs, and reimbursement issues. Pharmacists play a crucial role in coordinating therapy and providing support for patients.
AMERICAN JOURNAL OF MANAGED CARE
(2021)
Article
Hematology
Christian Augsberger, Gerulf Hanel, Wei Xu, Vesna Pulko, Lydia Jasmin Hanisch, Angelique Augustin, John Challier, Katharina Hunt, Binje Vick, Pier Eduardo Rovatti, Christina Krupka, Maurine Rothe, Anne Schonle, Johannes Sam, Emmanuelle Lezan, Axel Ducret, Daniela Ortiz-Franyuti, Antje-Christine Walz, Jorg Benz, Alexander Bujotzek, Felix S. Lichtenegger, Christian Gassner, Alejandro Carpy, Victor Lyamichev, Jigar Patel, Nikola Konstandin, Antje Tunger, Marc Schmitz, Michael Von Bergwelt-Baildon, Karsten Spiekermann, Luca Vago, Irmela Jeremias, Estelle Marrer-Berger, Pablo Umana, Christian Klein, Marion Subklewe
Summary: The novel T-cell bispecific (TCB) antibody targets intracellular antigens, recognizing multiple leukemia-associated targets. WT1-TCB demonstrates potent killing of AML cells through various methods, with enhanced cytotoxicity when combined with immunomodulatory drugs.
Article
Hematology
Sarah J. Nagle, Catherine Murphree, Philipp W. Raess, Levanto Schachter, Andy Chen, Brandon Hayes-Lattin, Eneida Nemecek, Richard T. Maziarz
Summary: CAR T-cell therapy is effective in treating patients with R/R DLBCL, but it is associated with significant prolonged hematologic toxicity (PHT) that can affect patients' survival rates. Risk factors associated with PHT include CRS, the use of tocilizumab or steroids, peak levels of ferritin and C-reactive protein. More research is needed to further investigate PHT and establish management standards.
AMERICAN JOURNAL OF HEMATOLOGY
(2021)
Review
Cell Biology
Laura Gragnani, Serena Lorini, Silvia Marri, Anna Linda Zignego
Summary: Notch receptors play critical roles in fundamental cellular processes and are implicated in hematopoiesis, angiogenesis, and various human malignancies. They could serve as potential therapeutic targets for hematological cancers.
Article
Oncology
Christos Georgiadis, Jane Rasaiyaah, Soragia Athina Gkazi, Roland Preece, Aniekan Etuk, Abraham Christi, Waseem Qasim
Summary: The use of base editing technology allows for the generation of CAR T cells with resistance to T cell fratricide, enabling enhanced cytotoxic effects against specific targets. Co-cultured 3CAR and 7CAR cells exhibit high cytotoxicity, particularly effective against CD3 + CD7 + T-ALL targets.
Article
Immunology
Zilong Guo, Yirui Zhang, Mingpeng Fu, Liang Zhao, Zhen Wang, Zhuoshuo Xu, Huifen Zhu, Xiaoli Lan, Guanxin Shen, Yong He, Ping Lei
Summary: The transferrin receptor (TfR) is being evaluated as an alternative target for CAR T cell therapy, showing potent cytotoxic effects against hematological malignancies. This suggests TfR could potentially broaden and enhance the therapeutic efficacy of CAR T cells, making it a promising universal target for further research.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Oezcan Cinar, Bernadette Brzezicha, Corinna Grunert, Peter Michael Kloetzel, Christin Beier, Caroline Anna Peuker, Ulrich Keller, Antonio Pezzutto, Antonia Busse
Summary: Adoptive transfer of T cells engineered to target specific mutations in B-cell lymphoma has shown promising results in preclinical studies, suggesting a potential novel treatment strategy with high tumor specificity. The engineered T cells exhibited mutation-specific reactivity and therapeutic efficacy in killing lymphoma cell lines carrying the targeted mutation. Initial safety screening also indicated a lack of off-target reactivity, supporting the feasibility and safety of using mutation-specific TCRs for precision therapy in a subgroup of B-cell malignancies.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Cell Biology
Nafiseh Maghsoodi, Mohammadrasul Zareinejad, Ali Golestan, Elham Mahmoudi Maymand, Amin Ramezani
Summary: This study aimed to produce and evaluate a novel αCD8/CD19 BiTE protein with direct targeting capability on CD8+ T-cells. The results showed that the recombinant αCD8/CD19 protein exhibited significant granzyme B production, cytotoxic activity, and proliferation potential in the presence of IL-2 and tumor target cells.
CELLULAR IMMUNOLOGY
(2023)
Review
Immunology
Xiaomin Zhang, Lingling Zhu, Hui Zhang, Shanshan Chen, Yang Xiao
Summary: CAR-T cell therapy has shown significant success in the treatment of hematological malignancies, but challenges remain in terms of adverse events and resistance mechanisms.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Roald Pfannes, Arkadiusz Pierzchalski, Ambra Maddalon, Alexandra Simion, Christos C. Zouboulis, Gerhard Behre, Ana Claudia Zenclussen, Sabine Westphal, Stefan Fest, Gunda Herberth
Summary: This study evaluated the adaptive immune response elicited after SARS-CoV-2 vaccination in cancer patients, specifically hematologic malignancy patients. The results showed that hematologic malignancy patients developed a robust cellular immune response to the vaccine, especially CD4 and Tfh cell responses. Immunomodulatory treatment before vaccination may enhance the antigen-specific immune response. These findings suggest that a strong cellular immune response is crucial for preventing SARS-CoV-2 infection in hematologic malignancy patients.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Tianning Gu, Meng Zhu, He Huang, Yongxian Hu
Summary: This review discusses the challenges of relapse after CAR-T cell therapy in B-cell malignancies. The factors contributing to relapse include intrinsic factors of tumor cells and the unique construction of CAR-T cells, while complex interactions among CAR-T cells, tumor cells, and the tumor microenvironment also affect efficacy and persistence.
JOURNAL OF ZHEJIANG UNIVERSITY-SCIENCE B
(2022)
Article
Hematology
Martin G. Klatt, Tao Dao, Zhiyuan Yang, Jianying Liu, Sung Soo Mun, Megan M. Dacek, Hanzhi Luo, Thomas J. Gardner, Christopher Bourne, Leila Peraro, Zita E. H. Aretz, Tanya Korontsvit, Michael Lau, Michael G. Kharas, Cheng Liu, David A. Scheinberg
Summary: Mass spectrometry identified a non-immunogenic HLA ligand as a target for CAR T-cell therapy, which showed broad effectiveness against multiple cancer types, particularly hematologic cancers, and had no toxic effects on healthy cells.
Review
Oncology
Lili Li, Luqin Wang, Qinhua Liu, Zhonghui Wu, Yulong Zhang, Ruixiang Xia
Summary: This study assessed the efficacy and safety of CD22 and CD19/CD22 CAR-T cell therapy for hematologic malignancies by summarizing existing evidence. The results showed that both CD22 and CD19/CD22 CAR-T immunotherapy demonstrated favorable efficacy and acceptable adverse events. Well-designed and large sample-sized clinical trials are needed for further validation.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Marco Dicanio, Matteo Giaccherini, Alyssa Clay-Gilmour, Angelica Macauda, Juan Sainz, Mitchell J. Machiela, Malwina Rybicka-Ramos, Aaron D. Norman, Agata Tyczynska, Stephen J. Chanock, Torben Barington, Shaji K. Kumar, Parveen Bhatti, Wendy Cozen, Elizabeth E. Brown, Anna Suska, Eva K. Haastrup, Robert Z. Orlowski, Marek Dudzinski, Ramon Garcia-Sanz, Marcin Kruszewski, Joaquin Martinez-Lopez, Katia Beider, Elzbieta Iskierka-Jazdzewska, Matteo Pelosini, Sonja Berndt, Malgorzata Razny, Krzysztof Jamroziak, S. Vincent Rajkumar, Artur Jurczyszyn, Annette Juul Vangsted, Pilar Garrido Collado, Ulla Vogel, Jonathan N. Hofmann, Mario Petrini, Aleksandra Butrym, Susan L. Slager, Elad Ziv, Edyta Subocz, Graham G. Giles, Niels Frost Andersen, Grzegorz Mazur, Marzena Watek, Fabienne Lesueur, Michelle A. T. Hildebrandt, Daria Zawirska, Lene Hyldahl Ebbesen, Herlander Marques, Federica Gemignani, Charles Dumontet, Judit Varkonyi, Gabriele Buda, Arnon Nagler, Agnieszka Druzd-Sitek, Xifeng Wu, Katalin Kadar, Nicola J. Camp, Norbert Grzasko, Rosalie G. Waller, Celine Vachon, Federico Canzian, Daniele Campa
Summary: The aim of this study was to identify novel pleiotropic variants involved in multiple myeloma (MM) risk. Through analysis of 28,684 single nucleotide polymorphisms (SNPs), DNAJB4-rs34517439-A was found to be associated with an increased risk of developing MM.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Letter
Hematology
Oren Pasvolsky, Rima M. Saliba, Adeel Masood, Ali H. Mohamedi, Mark R. Tanner, Qaiser Bashir, Samer Srour, Neeraj Saini, Jeremy Ramdial, Yago Nieto, Hans C. Lee, Krina K. Patel, Partow Kebriaei, Sheeba K. Thomas, Donna M. Weber, Robert Z. Orlowski, Elizabeth J. Shpall, Richard E. Champlin, Muzaffar H. Qazilbash
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Oncology
Minghao Dang, Ruiping Wang, Hans C. Lee, Krina K. Patel, Melody R. Becnel, Guangchun Han, Sheeba K. Thomas, Dapeng Hao, Yanshuo Chu, Donna M. Weber, Pei Lin, Zuzana Lutter-Berka, David A. Berrios Nolasco, Mei Huang, Hima Bansal, Xingzhi Song, Jianhua Zhang, Andrew Futreal, Luz Yurany Moreno Rueda, David E. Symer, Michael R. Green, Cristhiam M. Rojas Hernandez, Michael Kroll, Vahid Afshar-Khargan, Libere J. Ndacayisaba, Peter Kuhn, Sattva S. Neelapu, Robert Z. Orlowski, Linghua Wang, Elisabet E. Manasanch
Summary: In this study, single-cell RNA and B cell receptor sequencing were used to analyze data from 52 patients with myeloma precursors. The study revealed early genomic drivers, distinct transcriptional features, and different clonal expansion patterns in hyperdiploid and non-hyperdiploid samples. Intra-patient heterogeneity was observed, along with unique patterns of evolution from myeloma precursor disease to myeloma. Additionally, distinctive characteristics of the microenvironment associated with specific genomic changes in myeloma cells were identified. These findings provide valuable insights into myeloma precursor disease progression and have implications for patient risk stratification, biomarker discovery, and potential clinical applications.
Editorial Material
Oncology
Thierry Facon, Shaji K. Kumar, Torben Plesner, Robert Z. Orlowski, Philippe Moreau, Nizar Bahlis, Supratik Basu, Hareth Nahi, Cyrille Hulin, Hang Quach, Hartmut Goldschmidt, Aurore Perrot, Katja Weisel, Noopur Raje, Margaret Macro, Laurent Frenzel, Xavier Leleu, Jianping Wang, Rian Van Rampelbergh, Clarissa M. Uhlar, Jessica Vermeulen, Joana Duran, Fredrik Borgsten, Saad Z. Usmani
Article
Pathology
Fatima Zahra Jelloula, Andres E. Quesadaa, Richard K. Yanga, Shaoying Lia, Wei Wanga, Jie Xua, Guilin Tanga, C. Cameron Yina, Hong Fanga, Siba El Husseinb, Joseph Khourya, Roland L. Bassettc, Guillermo Garcia-Manerod, Elizabet E. Manasanche, Robert Z. Orlowskie, Muzaffar H. Qazilbashf, Keyur P. Patela, L. Jeffrey Medeirosa, Pei Lina
Summary: The development of therapy-related myeloid neoplasms (t-MN) is a rare complication in myeloma patients treated with novel therapies. Compared with a control group, these t-MNs were more likely to occur after multiple treatments and have a longer latency period in patients who received high-dose melphalan-based autologous stem cell transplantation (HDM-ASCT).
Article
Oncology
Oren Pasvolsky, Denai R. Milton, Mikael Rauf, Sassine Ghanem, Adeel Masood, Ali H. Mohamedi, Mark R. Tanner, Qaiser Bashir, Samer Srour, Neeraj Saini, Paul Lin, Jeremy Ramdial, Yago Nieto, Guilin Tang, Hans C. Lee, Krina K. Patel, Partow Kebriaei, Sheeba K. Thomas, Donna M. Weber, Robert Z. Orlowski, Katy Rezvani, Richard Champlin, Elizabeth J. Shpall, Pei Lin, Muzaffar H. Qazilbash
Summary: A retrospective analysis showed that the presence and degree of clonal plasma cells (CPC) in the autograft were highly predictive of inferior progression free survival (PFS) and overall survival (OS) in multiple myeloma (MM) patients undergoing autologous hematopoietic stem cell transplantation (autoHCT).
BLOOD CANCER JOURNAL
(2023)
Article
Oncology
Nianyi Li, Pei Lin, Zhuang Zuo, M. James You, Wen Shuai, Robert Orlowski, Elisabet E. Manasanch, Shaoying Li, Jie Xu, Sofia Garces, Fatima Zahra Jelloul, Zhenya Tang, Wei Wang, L. Jeffrey Medeiros, C. Cameron Yin
Summary: This study found that mutations in the RAS-MAPK pathway, such as KRAS, NRAS, and BRAF, are associated with poor prognosis in various cancers, but the results in myeloma are inconsistent. It is shown that RAS/BRAF-mutated myeloma patients have shorter survival time and are associated with higher tumor burden and complex genetic variations.
Review
Chemistry, Medicinal
Upasana Ray, Robert Z. Orlowski
Summary: Multiple myeloma is often treated with monoclonal antibodies targeting specific markers or as antibody-drug conjugates. There are several approved antibodies for treatment, such as daratumumab and isatuximab targeting CD38, elotuzumab targeting Signaling lymphocytic activation molecule family member 7, and teclistamab targeting BCMA. Belantamab mafodotin is an ADC that gained attention but faced withdrawal due to negative Phase III results. Despite this setback, there are other ADCs in development targeting BCMA or other plasma cell surface markers. Overall, ADCs have potential as part of chemotherapy against myeloma.
Article
Hematology
Oren Pasvolsky, Denai R. Milton, Adeel Masood, Sophiya S. Sami, Mark R. Tanner, Qaiser Bashir, Samer Srour, Neeraj Saini, Paul Lin, Jeremy Ramdial, Yago Nieto, Arsalan Saeed, Hans C. Lee, Krina K. Patel, Partow Kebriaei, Sheeba K. Thomas, Donna M. Weber, Robert Z. Orlowski, Elizabeth J. Shpall, Richard E. Champlin, Muzaffar H. Qazilbash
Summary: The optimal duration of Len maintenance for MM patients after autoHCT is uncertain. A retrospective analysis was conducted on MM patients who underwent upfront autoHCT followed by single-agent Len maintenance between 2005 and 2021. The results showed that longer maintenance duration, even beyond 5 years, was associated with improved survival. However, longer maintenance duration was also linked to a higher risk of developing a second primary malignancy (SPM).
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Hematology
Oren Pasvolsky, Curtis Marcoux, Denai R. Milton, Mark R. Tanner, Qaiser Bashir, Samer Srour, Neeraj Saini, Paul Lin, Jeremy Ramdial, Yago Nieto, Hans C. Lee, Krina K. Patel, Partow Kebriaei, Priti Tewari, Lindsay Crawford-Suber, Sheeba K. Thomas, Donna M. Weber, Robert Z. Orlowski, Elizabeth J. Shpall, Richard E. Champlin, Muzaffar H. Qazilbash
Summary: This study analyzed the data of 117 young adults with multiple myeloma (MM) undergoing autologous transplantation and found that auto-HCT had a favorable outcome for them. Furthermore, the survival of younger MM patients improved with the availability of novel anti-myeloma drugs in recent years. Depth of response following transplant was a key predictor of survival.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Multidisciplinary Sciences
Matthew Zibelman, Alexander W. MacFarlane, Kimberly Costello, Thomas McGowan, John O'Neill, Rutika Kokate, Hossein Borghaei, Crystal S. Denlinger, Efrat Dotan, Daniel M. Geynisman, Angela Jain, Lainie Martin, Elias Obeid, Karthik Devarajan, Karen Ruth, R. Katherine Alpaugh, Essel Al-Saleem Dulaimi, Edna Cukierman, Margret Einarson, Kerry S. Campbell, Elizabeth R. Plimack
Summary: This study reports the results of a phase I dose escalation trial of nivolumab in combination with IFN-γ in patients with advanced solid tumors. The combination therapy showed good safety and achieved therapeutic effects in some patients, suggesting that the combination of immune checkpoint blockade and IFN-γ may be an effective treatment strategy for cancer.
NATURE COMMUNICATIONS
(2023)
Article
Hematology
Peter M. Voorhees, Douglas W. Sborov, Jacob Laubach, Jonathan L. Kaufman, Brandi Reeves, Cesar Rodriguez, Ajai Chari, Rebecca Silbermann, Luciano J. Costa, Larry D. Anderson, Nitya Nathwani, Nina Shah, Naresh Bumma, Yvonne A. Efebera, Sarah A. Holstein, Caitlin Costello, Andrzej Jakubowiak, Tanya M. Wildes, Robert Z. Orlowski, Kenneth H. Shain, Andrew J. Cowan, Shira Dinner, Huiling Pei, Annelore Cortoos, Sharmila Patel, Thomas S. Lin, Saad Z. Usmani, Paul G. Richardson
Summary: In transplantation-eligible patients with newly diagnosed multiple myeloma, the addition of daratumumab to RVd improved the depth of response and progression-free survival.
LANCET HAEMATOLOGY
(2023)
Article
Oncology
Sonia M. Setayesh, Libere J. Ndacayisaba, Kate E. Rappard, Valerie Hennes, Luz Yurany Moreno Rueda, Guilin Tang, Pei Lin, Robert Z. Orlowski, David E. Symer, Elisabet E. Manasanch, Stephanie N. Shishido, Peter Kuhn
Summary: This study demonstrates the applicability of single-cell high-definition liquid biopsy assay and imaging mass cytometry to characterize the proteomic profile of multiple myeloma. It identifies potential therapeutic targets and reveals the differential expression of clinical markers across different stages of the disease.
NPJ PRECISION ONCOLOGY
(2023)
Article
Hematology
Saurabh Chhabra, Natalie Callander, Nicole L. Watts, Luciano J. Costa, Bicky Thapa, Jonathan L. Kaufman, Jacob Laubach, Douglas W. Sborov, Brandi Reeves, Cesar Rodriguez, Ajai Chari, Rebecca Silbermann, Larry D. Anderson, Susan Bal, Binod Dhakal, Nitya Nathwani, Nina Shah, Eva Medvedova, Naresh Bumma, Sarah A. Holstein, Caitlin Costello, Andrzej Jakubowiak, Tanya M. Wildes, Timothy Schmidt, Robert Z. Orlowski, Kenneth H. Shain, Andrew J. Cowan, Bhagirathbhai Dholaria, R. Frank Cornell, James H. Jerkins, Huiling Pei, Annelore Cortoos, Sharmila Patel, Thomas S. Lin, Saad Z. Usmani, Paul G. Richardson, Peter M. Voorhees
Summary: For eligible patients with newly diagnosed multiple myeloma (NDMM), standard of care includes induction therapy followed by autologous stem cell transplantation (ASCT). Daratumumab as monotherapy and in combination treatment is approved across multiple lines of therapy for multiple myeloma (MM), and lenalidomide is an effective and commonly used agent for induction and maintenance therapy in MM. However, there is concern that lenalidomide and daratumumab given as induction therapy might impair mobilization of stem cells for ASCT.
TRANSPLANTATION AND CELLULAR THERAPY
(2023)
Article
Hematology
Ethan P. Damron, Muzaffar H. Qazilbash, Penny Q. Fang, Susan Y. Wu, Bouthaina S. Dabaja, Gabriela Rondon, Chitra Hosing, Richard E. Champlin, Qaiser Bashir, Elizabeth J. Shpall, Mark K. Knafl, Hans C. Lee, Elisabet E. Manasanch, Krina Patel, Sheeba K. Thomas, Robert Z. Orlowski, Donna M. Weber, Chelsea C. Pinnix, Jillian R. Gunther
Summary: The primary treatment of multiple myeloma (MM) often includes systemic induction therapy (SIT) and autologous stem cell transplantation (ASCT). However, radiation therapy (RT) is sometimes avoided due to concerns about its effect on peripheral blood progenitor cell (PBPC) collection for ASCT. This study retrospectively examined the possible impact of RT on PBPC collection in MM patients. The results showed that RT prior to ASCT did not impair the successful collection of PBPCs.
TRANSPLANTATION AND CELLULAR THERAPY
(2023)
