Advances in cell and gene therapy最新文献

{"title":"CD276 as a novel CAR NK-92 therapeutic target for neuroblastoma","authors":"Stefan Grote,&nbsp;Kenneth Chun-Ho Chan,&nbsp;Caroline Baden,&nbsp;Hans Bösmüller,&nbsp;Mihály Sulyok,&nbsp;Leonie Frauenfeld,&nbsp;Martin Ebinger,&nbsp;Rupert Handgretinger,&nbsp;Sabine Schleicher","doi":"10.1002/acg2.105","DOIUrl":"10.1002/acg2.105","url":null,"abstract":"<p>Despite advanced understanding of its biology and improvements in standard of care treatment, the outcome for children with neuroblastoma (NB), the most common solid extracranial tumor in pediatrics, remains poor. Particularly, frequent relapse and high mortality rates of high-risk NB patients necessitate new therapeutic approaches such as chimeric antigen receptor (CAR)-modified immune cells. CAR T cells recently showed incredible clinical response targeting CD19 and CD22 in hematological malignancies. However, targeting solid cancers remains a difficult challenge and production of autologous CAR T-cell products still requires an extensive manufacturing process. The well-established natural killer (NK)-92 cell line provides a promising alternative to produce “off-the-shelf” CAR-modified effector cells. In the present study, we demonstrate that the immune checkpoint molecule B7-H3 (CD276) is aberrantly expressed on NB cells. Second generation CD276-CAR-engineered but not parental NK-92 cells were capable of specific and long-term elimination of NB cells in vitro while sparing CD276-negative cancer cells. Furthermore, CD276-CAR NK-92 cells showed increased cytotoxicity in a three-dimensional NB spheroid model which can recapitulate in vivo morphology as well as cell connectivity, polarity, gene expression, and tissue architecture, thereby, bridging the gap between in vitro and in vivo models. CD276-CAR NK-92 cells produced a multitude of NK effector molecules as well as pro-inflammatory cytokines that can stimulate the immune system. CD276-CAR surface expression and cytotoxic effector function remained stable for more than 6 months. Data show that CD276-CAR NK-92 may be a promising treatment option for patients with high-risk NB.</p>","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/acg2.105","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42059101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prolonged neurotoxicity in a lymphoma patient after CD19-directed CAR T-cell therapy: A case report and brief review of the literature","authors":"Uri Greenbaum,&nbsp;Jeremy L. Ramdial,&nbsp;Amanda Olson,&nbsp;Yago Nieto,&nbsp;Paolo Strati,&nbsp;Sairah Ahmed,&nbsp;Sattva S. Neelapu,&nbsp;Sudhakar Tummala,&nbsp;Linda Chi,&nbsp;Elizabeth J. Shpall,&nbsp;Partow Kebriaei","doi":"10.1002/acg2.104","DOIUrl":"10.1002/acg2.104","url":null,"abstract":"<p>As the field of cancer therapeutics moves increasingly toward targeted and cellular therapies, this evolution comes with new hurdles. Toxicity of these therapies can result in serious adverse events that can become life-threatening. In particular, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are now the most common adverse effects resulting from chimeric antigen receptor (CAR) T-cell therapy. Furthermore, CAR T cells are reported to cause hyperactivation of macrophages, which in extreme cases results in hemophagocytic lymphohistiocytosis (HLH). These toxic effects result from cytokines released as a direct effect of the therapy. Physicians are evaluating inflammatory markers to monitor longitudinally cytokine stimulation and immune activation after therapy, which can help predict and gauge the severity of the cytokine storm. Prompt recognition of toxic effects and rapid intervention are essential in the management of patients receiving CAR T-cell therapy. Despite intervention, some patients still experience severe and prolonged ICANS. Herein we present a patient with lymphoma who developed prolonged ICANS and reviewed the literature on neurotoxicity and macrophage activation resulting from CD19-directed CAR T-cell therapy.</p>","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/acg2.104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42803058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combining the disease risk index and hematopoietic cell transplant co-morbidity index provides a comprehensive prognostic model for CD34+-selected allogeneic transplantation","authors":"Christina Cho,&nbsp;Patrick Hilden,&nbsp;Scott T. Avecilla,&nbsp;Juliet N. Barker,&nbsp;Hugo Castro-Malaspina,&nbsp;Sergio A. Giralt,&nbsp;Boglarka Gyurkocza,&nbsp;Ann A. Jakubowski,&nbsp;Molly A. Maloy,&nbsp;Richard J. O’Reilly,&nbsp;Esperanza B. Papadopoulos,&nbsp;Jonathan U. Peled,&nbsp;Doris M. Ponce,&nbsp;Brian Shaffer,&nbsp;Roni Tamari,&nbsp;Marcel R. M. van den Brink,&nbsp;James W. Young,&nbsp;Pere Barba,&nbsp;Miguel-Angel Perales","doi":"10.1002/acg2.103","DOIUrl":"https://doi.org/10.1002/acg2.103","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>T cell depletion by CD34⁺ cell selection of hematopoietic stem cell allografts ex vivo reduces the incidence and severity of GvHD, without increased risk of relapse in patients with acute leukemia in remission or MDS. The optimal candidate for CD34⁺-selected HCT remains unknown, however.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To determine outcomes based on both disease- and patient-specific factors, we evaluated a prognostic model combining the Disease Risk Index (DRI) and Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI), an approach recently shown to predict overall survival in a broad population of allograft recipients (Kongtim P, Parmar S, Milton DR, et al. Impact of a novel prognostic model, hematopoietic cell transplant-composite risk (HCT-CR), on allogeneic transplant outcomes in patients with acute myeloid leukemia and myelodysplastic syndrome. <i>Bone Marrow Transplant</i>. 2019;54(6):839-48).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This was a retrospective analysis of 506 adult recipients of first allogeneic HCT with CD34 + selected PBSCs from 7/8- or 8/8-matched donors for AML (n = 290), ALL (n = 72), or MDS (n = 144). The Kaplan-Meier method estimated OS and RFS. The cumulative incidence method for competing risks estimated relapse and non-relapse mortality (NRM). We evaluated the univariate association between variables of interest and OS and RFS using the log-rank test. Cox regression models assessed the adjusted effect of covariates on OS/RFS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Stratification of patients based on a composite of DRI (low/intermediate vs high/very high) and HCT-CI (0-2 vs ≥3) revealed differences in OS and RFS between the four groups. Compared with reference groups of patients with low/intermediate DRI and low or high HCT-CI, those with high DRI had a greater risk of death (HR 2.30; 95% CI 1.39, 3.81) and relapse or death (HR 2.50; 95% CI 1.55, 4.05) than patients with any HCT-CI but low/intermediate DRI (HR death 1.80; 95% CI 1.34, 2.43; HR relapse/death 1.68; 95% CI 1.26, 2.24).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions and Clinical Implications</h3>\u0000 \u0000 <p>A model combining DRI and HCT-CI predicted survival after CD34⁺ cell-selected HCT. Application of this combined model to other cohorts, both in retrospective analyses and prospective trials, will enhance clinical decision making and patient selection for different transplant approaches.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/acg2.103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71980925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of thrombopoietin receptor agonists after hematopoietic progenitor cell transplantation","authors":"Sara Singer,&nbsp;Basem M. William","doi":"10.1002/acg2.102","DOIUrl":"10.1002/acg2.102","url":null,"abstract":"<p>Hematopoietic stem cell transplant (HCT) is used with increasing frequency for the treatment of malignant and nonmalignant diseases. Thrombocytopenia is a common complication following HCT and is associated with decreased survival. Supportive care with platelet transfusion requires significant resources, reduces quality of life, and is associated with several adverse effects including transfusion reaction, infection, and alloimmunization. Thrombopoeitin receptor agonists (TPO-RA) have been found to be safe and effective for the treatment of immune mediated thrombocytopenia, thrombocytopenia related to bone marrow failure syndromes, and thrombocytopenia of chronic liver disease. We hereby discuss in this review the evidence for use of TPO-RA for the management of thrombocytopenia after HCT.</p>","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/acg2.102","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48055694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid production of clinical-grade SARS-CoV-2 specific T cells","authors":"Wing Leung,&nbsp;Teck Guan Soh,&nbsp;Yeh Ching Linn,&nbsp;Jenny Guek-Hong Low,&nbsp;Jiashen Loh,&nbsp;Marieta Chan,&nbsp;Wee Joo Chng,&nbsp;Liang Piu Koh,&nbsp;Michelle Li-Mei Poon,&nbsp;King Pan Ng,&nbsp;Chik Hong Kuick,&nbsp;Thuan Tong Tan,&nbsp;Lip Kun Tan,&nbsp;Michaela Su-fern Seng","doi":"10.1002/acg2.101","DOIUrl":"10.1002/acg2.101","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To determine whether the frequencies of SARS-CoV-2-specific T cells are sufficiently high in the blood of convalescent donors and whether it is technically feasible to manufacture clinical-grade products overnight for T-cell therapy and assessment of COVID-19 immunity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>One unit of whole blood or leukapheresis was collected from each donor following standard blood bank practices. The leukocytes were stimulated using overlapping peptides of SARS-CoV-2, covering the immunodominant sequence domains of the S protein and the complete sequence of the N and M proteins. Thereafter, functionally reactive cells were enriched overnight using an automated device capturing IFNγ-secreting cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>From 1 × 10⁹ leukocytes, a median of 0.98 × 10⁶ (range 0.56-2.95) IFNγ + T cells were produced from each of the six donors, suggesting a high frequency of SARS-CoV-2 reactive T cells in their blood, even though only one donor had severe COVID-19 requiring mechanical ventilation whereas the other five donors had minor symptoms. A median of 57% of the enriched T cells were IFNγ+ (range 20%-74%), with preferential enrichment of CD56+ T cells and effector memory T cells. TCRVβ-spectratyping confirmed distinctively tall oligoclonal peaks in final products. With just six donors, the probability that a recipient would share at least one HLA allele with one of the donors is &gt;88% among Caucasian, &gt;95% among Chinese, &gt;97% among Malay, and &gt;99% among Indian populations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>High frequencies of rapid antigen-reactive T cells were found in convalescent donors, regardless of severity of COVID-19. The feasibility of clinical-grade production of SARS-CoV-2-specific T cells overnight for therapeutics and diagnostics is revealed.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/acg2.101","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38303163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering oncolytic vaccinia virus to redirect macrophages to tumor cells","authors":"Felicia Cao,&nbsp;Phuong Nguyen,&nbsp;Bangxing Hong,&nbsp;Christopher DeRenzo,&nbsp;Nino C. Rainusso,&nbsp;Tania Rodriguez Cruz,&nbsp;Meng-Fen Wu,&nbsp;Hao Liu,&nbsp;Xiao-Tong Song,&nbsp;Masataka Suzuki,&nbsp;Lisa L. Wang,&nbsp;Jason T. Yustein,&nbsp;Stephen Gottschalk","doi":"10.1002/acg2.99","DOIUrl":"10.1002/acg2.99","url":null,"abstract":"<p>Oncolytic virotherapy has been tested in numerous early phase clinical studies. However, the antitumor activity of oncolytic viruses thus far has been limited. Numerous strategies are being explored to enhance their antitumor activity by activating the adaptive arm of the immune system. We reasoned that it might also be possible to engineer oncolytic viruses to redirect tumor-associated macrophages to tumor cells for therapeutic benefit. We engineered an oncolytic vaccinia virus (VV) to disrupt the CD47/SIRPα interaction by expressing a chimeric molecule that consists of the ectodomain of SIRPα and the Fc domain of IgG4 (SIRPα-Fc-VV). SIRPα-Fc-VV readily replicated in tumor cells and redirected M1 as well as M2 macrophages to tumor cells in vitro. In contrast, control VVs that either encoded YFP (YFP-VV) or SIRPα (SIRPα-VV) did not. In vivo, SIRPα-Fc-VV had greater antitumor activity than YFP-VV and SIRPα-VV in an immune competent osteosarcoma model resulting in a significant survival advantage. Pretreatment with cytoxan further augmented the antitumor activity of SIRPα-Fc-VV. Thus, arming oncolytic viruses with SIRPα-Fc may present a promising strategy to enhance their antitumor activity for the virotherapy of solid tumors.</p>","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/acg2.99","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25586081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytokine syndromes associated with hematopoietic cellular therapy","authors":"Thomas R. Spitzer","doi":"10.1002/acg2.98","DOIUrl":"10.1002/acg2.98","url":null,"abstract":"<p>The clinical manifestations of excess production of proinflammatory cytokines associated with hematopoietic cell therapy are being increasingly recognized. While these manifestations are all forms of a cytokine release syndrome (CRS), the terminology to date has focused on the clinical scenarios in which they occur (eg, graft vs host disease [GVHD] or engraftment syndrome [ES] following hematopoietic cell transplantation or CRS following immune effector cell therapy). The data regarding cytokine profiles in these conditions are limited by the variable methods of assessment and which cytokines are measured. Overlapping cytokine profiles are seen in these conditions, but distinct differences in the profiles have also been described (eg, for acute GVHD and ES). Targeted interventions have been developed based on these profiles with some (eg, anti-interleukin-6 receptor antibody therapy for CRS after immune effector cell therapy) showing more promise than others. Future strategies include the evaluation of monoclonal antibodies against more recently described cytokines and the increasing use of less specific inhibitors of cytokine production such as the Janus Kinase/Transducer and Activator of Transcription signaling inhibitors.</p>","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/acg2.98","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41350402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leveraging minimal residual disease to reassess autologous hematopoietic cell transplantation in multiple myeloma","authors":"Susan Bal,&nbsp;Luciano J. Costa","doi":"10.1002/acg2.97","DOIUrl":"10.1002/acg2.97","url":null,"abstract":"<p>While the treatment landscape of multiple myeloma has evolved and expanded over the past decade, autologous hematopoietic cell transplantation remains an integral part of myeloma therapy. The availability of sensitive minimal residual disease (MRD) testing has allowed us to characterize the depth of response beyond traditional response assessment. It also provides an exceptional platform to rapidly study the benefit of each intervention and systemically appraise its incremental benefit. While relatively early in its development as a decision-making tool and faced with challenges such as standardization, it is prime time for MRD testing. The continued incorporation of MRD based endpoints into clinical trials and ultimately, into clinical practice, will result in individualized treatment strategies tailored to each patient resulting in minimum necessary treatment to obtain sustained disease control and long-term survival.</p>","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/acg2.97","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43904082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances & future prospects in newly diagnosed multiple myeloma patients","authors":"Issam Hamadeh,&nbsp;Shebli Atrash,&nbsp;Ashley Matusz Fisher,&nbsp;Maham A. Khan,&nbsp;Jordan Diana Robinson,&nbsp;Paul Barry,&nbsp;Saad Z. Usmani","doi":"10.1002/acg2.96","DOIUrl":"10.1002/acg2.96","url":null,"abstract":"<p>The overall survival (OS) in multiple myeloma (MM) has almost quadrupled over the past 2 decades. This improvement could be attributed to the introduction of novel agents in the schema of therapy which includes the following phases: induction, high dose melphalan/stem cell transplant, optional posttransplant consolidation and maintenance (Barlogie Total-Therapy schema). Because disease relapse is inevitable, additional treatment is generally needed to achieve remission. Emerging evidence suggests that assessment of minimal residual disease status following induction or autologous stem cell transplant could be predictive of duration of progression-free survival as well as OS. In an effort to prolong duration of first remission, various drug combinations are being evaluated in the front-line setting. The purpose of this paper is to provide a succint review of the current treatment paradigm of newly diagnosed MM and highlight the preliminary findings from some of the ongoing clinical trials which are likely to change current practice.</p>","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/acg2.96","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46164082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Approaching the first relapse after autologous transplant in multiple myeloma","authors":"Shebli Atrash,&nbsp;Issam Hamadeh,&nbsp;Ashley Matusz-Fisher,&nbsp;Ami Ndiaye,&nbsp;Manisha Bhutani,&nbsp;Peter M. Voorhees,&nbsp;Paul Barry,&nbsp;Saad Z. Usmani","doi":"10.1002/acg2.95","DOIUrl":"10.1002/acg2.95","url":null,"abstract":"<p>Multiple myeloma(MM) is an incurable plasma cell malignancy. Despite an improvement in OS over the past 2 decades, most patients do experience disease relapse. A subset of patients who experience an early disease relapse within 1-2 years posttransplant, and considered functional high-risk. Recent findings implicated high-risk cytogenetic features and minimal residual disease as negative prognostic factors, each independently associated with early relapse among autologous stem cell transplant recipients(ASCT). The spectrum of disease relapse could range from asymptomatic/biochemical to more aggressive forms such as plasma cell leukemia. Hence, it is imperative that therapy be tailored based on these patterns of relapse upon presentation. The past few years have witnessed an explosion in the armamentarium of second-line agents for the treatment of relapsed MM. Accordingly, choosing the optimal regimen has become quite challenging for the practicing clinician. In this review, we outline the approach for therapy selection, which takes into account underlying comorbid conditions, duration of response, presence of high-risk features, etc Due to a better understanding of disease biology coupled with the advances in molecular techniques, the treatment landscape of relapsed MM (posttransplant) will most likely continue to evolve. Novel agents with distinct modes of action, such as immune therapies and novel oral agents are undergoing investigation in the relapsed setting. Once approved, these agents could potentially alter the course of the disease and possibly challenge the role of ASCT.</p>","PeriodicalId":72084,"journal":{"name":"Advances in cell and gene therapy","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/acg2.95","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46664798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}