Cancer journal最新文献

Beyond Immunomodulatory Drugs: Next-Generation Cereblon Modulators in Multiple Myeloma. 超越免疫调节药物：多发性骨髓瘤的下一代小脑调节剂。

IF 2.1 4区医学

Cancer journal Pub Date : 2026-09-01 Epub Date: 2026-09-25 DOI: 10.1097/PPO.0000000000000851

Lorenzo Cani, Roberto Mina, Sagar Lonial

{"title":"Beyond Immunomodulatory Drugs: Next-Generation Cereblon Modulators in Multiple Myeloma.","authors":"Lorenzo Cani, Roberto Mina, Sagar Lonial","doi":"10.1097/PPO.0000000000000851","DOIUrl":"10.1097/PPO.0000000000000851","url":null,"abstract":"Despite substantial improvements in survival over recent decades, multiple myeloma (MM) remains largely incurable, and most patients ultimately experience relapsed or refractory disease, highlighting the need for novel therapeutic strategies. Immunomodulatory drugs (IMiDs) have transformed MM treatment through direct antitumor and immune-enhancing effects mediated by cereblon modulation, while their ability to stimulate T-cell and NK-cell function has provided a strong rationale for combination with modern immunotherapies, including bispecific antibodies and chimeric antigen receptor (CAR) T-cell therapies. More recently, cereblon E3 ligase modulators (CELMoDs), such as iberdomide and mezigdomide, have emerged as next-generation cereblon-targeting agents with enhanced potency, deeper substrate degradation, and activity in lenalidomide- and pomalidomide-resistant settings. Clinical studies have demonstrated promising efficacy and manageable safety profiles across newly diagnosed and relapsed/refractory MM, including in heavily pretreated patients. In parallel, novel degraders such as cemsidomide have shown encouraging preliminary activity, further expanding the therapeutic potential of cereblon-directed approaches in MM. In this review, we aim to summarize the evolution of oral therapies in MM, focusing on the efficacy and safety of next-generation cereblon modulators and emerging cereblon-directed degraders.","PeriodicalId":9655,"journal":{"name":"Cancer journal","volume":"32 5","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149080012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Minimal Residual Disease (MRD) in Multiple Myeloma: From Prognostic Marker to Therapeutic Compass. 多发性骨髓瘤的微小残留病（MRD）：从预后标志物到治疗指南。

IF 2.1 4区医学

Cancer journal Pub Date : 2026-09-01 Epub Date: 2026-09-25 DOI: 10.1097/PPO.0000000000000846

Luis-Esteban Tamariz-Amador, Paula Rodriguez-Otero, Andrea Manubens, Marta Lasa, Carmen Gonzalez, Bruno Paiva, Jesús San-Miguel

引用次数: 0

T-Cell Redirecting Antibodies for the Treatment of Multiple Myeloma: Off-the-Shelf T-Cell Immunity. t细胞重定向抗体治疗多发性骨髓瘤：现成的t细胞免疫。

IF 2.1 4区医学

Cancer journal Pub Date : 2026-09-01 Epub Date: 2026-09-25 DOI: 10.1097/PPO.0000000000000847

Niels W C J van de Donk, Febe Smits, Chloe O'Neill, Jos Hoekman, Sandy Kruyswijk, Serena R Baglio, Sonja Zweegman, Charlotte L B M Korst

{"title":"T-Cell Redirecting Antibodies for the Treatment of Multiple Myeloma: Off-the-Shelf T-Cell Immunity.","authors":"Niels W C J van de Donk, Febe Smits, Chloe O'Neill, Jos Hoekman, Sandy Kruyswijk, Serena R Baglio, Sonja Zweegman, Charlotte L B M Korst","doi":"10.1097/PPO.0000000000000847","DOIUrl":"10.1097/PPO.0000000000000847","url":null,"abstract":"Bispecific antibodies (BsAbs) bind simultaneously to an antigen on the surface of multiple myeloma (MM) cells and to CD3 on the surface of T cells. This engagement leads to T-cell activation and degranulation, releasing perforin and granzymes, followed by the killing of the MM cell. Off-the-shelf available BsAbs targeting BCMA, GPRC5D, and FcRH5 have pronounced antitumor activity in heavily pretreated MM with cytokine-release syndrome, neutropenia, and infections as the most common side effects. To further improve clinical outcomes, BsAb-based combinations are being evaluated in earlier treatment lines, including newly diagnosed MM. Notably, the MajesTEC-3 trial established the combination of teclistamab and daratumumab as a new standard-of-care for relapsed/refractory MM as early as first relapse. The most common mechanism underlying acquired resistance to BsAbs is loss of antigen expression; therefore, dual-targeting strategies (combination of BsAbs targeting different tumor antigens or trispecific antibodies) are being intensively investigated to enhance the depth and duration of response.","PeriodicalId":9655,"journal":{"name":"Cancer journal","volume":"32 5","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Managing Novel CAR T-Cell Toxicities in Multiple Myeloma. 治疗多发性骨髓瘤的新型CAR - t细胞毒性。

IF 2.1 4区医学

Cancer journal Pub Date : 2026-09-01 Epub Date: 2026-09-25 DOI: 10.1097/PPO.0000000000000849

Kwan-Keat Ang, Jodi Lipof, Anupama Kumar, Lekha Mikkilineni, Alfred Chung, Shagun Arora, Peter Sayre, Jeffrey Wolf, Ajai Chari, Thomas Martin, Darren Pan

{"title":"Managing Novel CAR T-Cell Toxicities in Multiple Myeloma.","authors":"Kwan-Keat Ang, Jodi Lipof, Anupama Kumar, Lekha Mikkilineni, Alfred Chung, Shagun Arora, Peter Sayre, Jeffrey Wolf, Ajai Chari, Thomas Martin, Darren Pan","doi":"10.1097/PPO.0000000000000849","DOIUrl":"10.1097/PPO.0000000000000849","url":null,"abstract":"B-cell maturation antigen (BCMA) targeted chimeric antigen receptor T-cell (CAR-T) cell therapy has proven highly efficacious for relapsed multiple myeloma, inducing deep and durable remissions. Recent reporting has bolstered significant enthusiasm, describing upwards of one-third of patients in continued remission, 5 years following BCMA CAR-T without receiving any subsequent therapy, suggesting the possibility that this treatment may offer the hope of a cure. There are many well-characterized side effects from CAR-T, and mitigation strategies have been established to make this therapy safe. However, as the use of CAR-T cells has become more widespread, several novel and unanticipated side effects have emerged. These novel toxicities of CAR-T can be delayed, occurring within the first 3 to 6 months, and can be life-threatening or life-altering. Thus, early detection and timely management are essential. This comprehensive review will cover the diagnosis and management of common and emerging toxicities associated with CAR T-cell therapy for multiple myeloma.","PeriodicalId":9655,"journal":{"name":"Cancer journal","volume":"32 5","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149080007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tailoring Therapy for Frail and Elderly Myeloma Patients. 体弱多病和老年骨髓瘤患者的定制治疗。

IF 2.1 4区医学

Cancer journal Pub Date : 2026-09-01 Epub Date: 2026-09-25 DOI: 10.1097/PPO.0000000000000850

Thomas George, Raphael E Szalat

{"title":"Tailoring Therapy for Frail and Elderly Myeloma Patients.","authors":"Thomas George, Raphael E Szalat","doi":"10.1097/PPO.0000000000000850","DOIUrl":"10.1097/PPO.0000000000000850","url":null,"abstract":"Multiple myeloma is a plasma cell malignancy associated with heterogeneous clinical outcomes. The majority of patients are diagnosed during their seventh decade and often present with age-related comorbidities and organ dysfunction. Myeloma therapeutic landscape is rapidly evolving with the introduction of immune-based therapies, including monoclonal and bispecific antibodies and chimeric antigen receptor (CAR) T-cell therapies targeting CD38, BCMA, and GPRC5D. These novel therapies have led to deeper and more durable responses and have raised the possibility of functional or definitive cure. However, older and frail patients continue to experience poorer outcomes, higher toxicity rates, and substantial treatment attrition, representing a major unmet clinical challenge. In this review, we discuss current approaches to the assessment and management of frailty in patients with multiple myeloma, with a focus on optimizing frontline therapy and treatment at relapse in the era of the possible achievement of a cure. We highlight emerging data on cellular therapies in this population and the importance of individualized, goal-directed treatment strategies aimed at balancing efficacy, tolerability, and quality of life.","PeriodicalId":9655,"journal":{"name":"Cancer journal","volume":"32 5","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Toward a Cure in Multiple Myeloma: Redefining Induction Therapy and the Role of Autologous Stem Cell Transplant. 迈向治愈多发性骨髓瘤：重新定义诱导疗法和自体干细胞移植的作用。

IF 2.1 4区医学

Cancer journal Pub Date : 2026-09-01 Epub Date: 2026-09-25 DOI: 10.1097/PPO.0000000000000853

Advait Joshi, Benjamin R Puliafito, Diana D Cirstea, Andrew R Branagan, Joshua N Gustine, Rajib Shome, Cristina Panaroni, Andrew J Yee, Noopur S Raje

{"title":"Toward a Cure in Multiple Myeloma: Redefining Induction Therapy and the Role of Autologous Stem Cell Transplant.","authors":"Advait Joshi, Benjamin R Puliafito, Diana D Cirstea, Andrew R Branagan, Joshua N Gustine, Rajib Shome, Cristina Panaroni, Andrew J Yee, Noopur S Raje","doi":"10.1097/PPO.0000000000000853","DOIUrl":"10.1097/PPO.0000000000000853","url":null,"abstract":"The therapeutic goal in multiple myeloma (MM) is changing from long-term disease control to a potential cure. While anti-CD38-containing quadruplets have improved outcomes, relapses continue to occur in many patients. In recent years, advancements in immunotherapy have fundamentally changed this paradigm. Bispecific antibodies (BsAbs) and chimeric antigen receptor T-cells (CAR T-cells) have deepened responses and achieved sustained MRD negativity in an unprecedented way, raising the possibility of curing MM in a subset of patients. Recently, the International Myeloma Society (IMS) reached a consensus and discussed a framework to define cure. This review examines how novel immunotherapies are redefining frontline strategies in newly diagnosed MM (NDMM) and attempts to summarize how BsAbs, CAR T-cells, and cereblon E3 ligase modulators (CELMoDs) can be integrated into induction, consolidation, and maintenance phases. It also discusses the evolving role of autologous stem cell transplant (ASCT) in the immunotherapy era and MRD-guided treatment and discontinuation strategies. Together, this review attempts to provide a roadmap to fulfill the criteria for cure.","PeriodicalId":9655,"journal":{"name":"Cancer journal","volume":"32 5","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CAR-T Cell Therapy: Engineering Remission in Refractory Myeloma. CAR-T细胞疗法：难治性骨髓瘤的工程缓解。

IF 2.1 4区医学

Cancer journal Pub Date : 2026-09-01 Epub Date: 2026-09-25 DOI: 10.1097/PPO.0000000000000854

Adam S Sperling

{"title":"CAR-T Cell Therapy: Engineering Remission in Refractory Myeloma.","authors":"Adam S Sperling","doi":"10.1097/PPO.0000000000000854","DOIUrl":"10.1097/PPO.0000000000000854","url":null,"abstract":"Chimeric antigen receptor (CAR) T cells have rapidly reshaped the treatment of relapsed and refractory multiple myeloma (MM), progressing from an experimental salvage option to a therapy with a demonstrated overall survival advantage and durable, potentially curative remissions in a subset of patients. This review surveys the current evidence supporting their use, the biology underlying their successes and failures, established and emerging toxicities, and novel approaches that will define the field in the coming years. Approved products directed against B cell maturation antigen (BCMA) induce rapid and deep responses even in heavily pretreated patients, and long-term follow-up now suggests a meaningful fraction of patients achieve prolonged remission after a single infusion without maintenance therapy. These benefits are accompanied by distinctive toxicities that shape the risk-benefit calculus as therapy moves to earlier lines and even to treatment naïve patients. We discuss the determinants of response and relapse, as well as the mechanisms of antigen-positive and antigen-negative escape that next-generation approaches aim to overcome. These include novel antigen targets, multi-antigen and armored constructs, rapid manufacturing, and in vivo CAR generation, all with the goal of extending durable remissions to every patient.","PeriodicalId":9655,"journal":{"name":"Cancer journal","volume":"32 5","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149080016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Smoldering and Early Disease Interception. 阴燃和早期疾病拦截。

IF 2.1 4区医学

Cancer journal Pub Date : 2026-09-01 Epub Date: 2026-09-25 DOI: 10.1097/PPO.0000000000000848

Borja Puertas, Elena Alejo, María-Victoria Mateos

{"title":"Smoldering and Early Disease Interception.","authors":"Borja Puertas, Elena Alejo, María-Victoria Mateos","doi":"10.1097/PPO.0000000000000848","DOIUrl":"10.1097/PPO.0000000000000848","url":null,"abstract":"Smoldering multiple myeloma (SMM) is an asymptomatic precursor of multiple myeloma characterized by marked heterogeneity in the risk of progression. Current management relies on clinical risk stratification to identify patients who might benefit from early intervention. Models such as the 20/2/20 score and its International Myeloma Working Group refinement incorporate tumor burden and cytogenetic abnormalities, whereas emerging approaches integrating dynamic biomarkers, circulating tumor cells, genomic alterations, and immune signatures could further improve the prediction of progression if validated in larger cohorts. Randomized trials suggest that early treatment with lenalidomide-based regimens or anti-CD38 monoclonal antibodies delays progression and possibly improves survival in high-risk SMM, and daratumumab has been approved as an early intervention in high-risk SMM. More intensive immunotherapy-based strategies can achieve high rates of sustained measurable residual disease negativity, which might translate into durable disease control or even a cure. Future management will likely depend on biologically informed, risk-adapted strategies to balance early treatment benefits against overtreatment, together with safety profile and patients' preferences.","PeriodicalId":9655,"journal":{"name":"Cancer journal","volume":"32 5","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Monoclonal Antibodies and Antibody-Drug Conjugates: Expanding the Therapeutic Arsenal in Multiple Myeloma. 单克隆抗体和抗体-药物偶联物：扩大多发性骨髓瘤的治疗库。

IF 2.1 4区医学

Cancer journal Pub Date : 2026-09-01 Epub Date: 2026-09-25 DOI: 10.1097/PPO.0000000000000845

Ioannis Ntanasis-Stathopoulos, Evangelos Terpos, Meletios-Athanasios Dimopoulos

引用次数: 0

Crossing the Threshold to Cure in Multiple Myeloma. 跨越治愈多发性骨髓瘤的门槛。

IF 2.1 4区医学

Cancer journal Pub Date : 2026-09-01 Epub Date: 2026-09-25 DOI: 10.1097/PPO.0000000000000855

Adam S Sperling, Nikhil C Munshi

引用次数: 0