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1.
Sundar Jagannath Rafat Abonour Brian G.M. Durie Cristina Gasparetto James W. Hardin Mohit Narang Howard R. Terebelo Kathleen Toomey Lynne Wagner Shankar Srinivasan Amani Kitali Lihua Yue E.Dawn Flick Amit Agarwal Robert M. Rifkin 《Clinical Lymphoma, Myeloma & Leukemia》2018,18(7):480-485.e3
Background
The treatment landscape for multiple myeloma (MM) has undergone recent changes with the regulatory approval of several new therapies indicated for second- and later-line disease. Using data from Connect MM, the largest multisite, primarily community-based, prospective, observational registry of MM patients in the United States, selection of second-line treatments was evaluated during a 5-year period from 2010 to 2016.Patients and Methods
Eligible patients were aged ≥ 18 years, had newly diagnosed MM ≤ 2 months before study entry, and were followed for up to 8 years. Patients who received ≥ 2 lines of therapy were analyzed. “Tepee” plots of stacked area graphs differentiated treatments by color to allow visualization of second-line treatment trends in MM patients.Results
As of February 2017, 855 of 2897 treated patients had progressed to second-line treatment. Treatment selection was heterogeneous; shifting patterns of treatment choices coincided with the approval status of newer agents. The most common treatment regimens in the early part of the decade were lenalidomide and/or bortezomib, with or without dexamethasone, with increasing use of newer agents (carfilzomib, pomalidomide, daratumumab, and elotuzumab) and triplet combinations over time. The influence of the baseline patient characteristics of age, history of diabetes, peripheral neuropathy, and renal function on treatment choice was also examined.Conclusion
These findings indicate that community physicians are current in their MM management practices, with uptake of new drugs and acquaintance with results of randomized clinical trials using combinations almost concurrent with their regulatory approval and publication. 相似文献2.
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Paula Rodriguez-Otero Maialen Sirvent Ana Pilar González-Rodríguez Esperanza Lavilla Alfonso García de Coca José María Arguiñano Josep M. Martí Valentin Cabañas Cristina Motlló Erik de Cabo Cristina Encinas Ilda Murillo Jose Ángel Hernández-Rivas Ernesto Pérez-Persona Felipe Casado Antonia Sampol Ricarda García María Jesús Blanchard Jesús F. San Miguel 《Clinical Lymphoma, Myeloma & Leukemia》2021,21(6):413-420
IntroductionTreatment of relapsed/refractory multiple myeloma (RRMM) is highly challenging, especially for patients with disease refractory to initial therapy, and in particular for disease developing refractoriness to lenalidomide. Indeed, with currently approved treatments, median progression-free survival (PFS) in the lenalidomide-refractory setting is less than 10 months, reflecting the difficulty in treating this patient population. Pomalidomide is a second-generation immunomodulatory drug that has shown activity in lenalidomide-refractory disease in the setting of different combinations.Patients and MethodsA real-world study was conducted by the Spanish Myeloma group in a cohort of patients with RRMM treated with pomalidomide, cyclophosphamide, and dexamethasone (PomCiDex). One hundred patients were treated with a median of 3 prior lines of therapy.ResultsOverall response rate was 39%, with a clinical benefit rate of 93%. Median PFS was 7.6 months; median overall survival (OS) was 12.6 months. Median PFS and OS survival were consistent across the different subgroups analyzed. Prolonged PFS and OS were found in patients with responsive disease.ConclusionOur results compared favorably with those obtained with different pomalidomide-based combinations in a similar patient population. PomCiDex remains a manageable, cost-effective, and all-oral triplet combination for RRMM patients. 相似文献
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《Clinical Lymphoma, Myeloma & Leukemia》2020,20(1):53-56
BackgroundNon-secretory multiple myeloma (NSMM) is a rare subtype of multiple myeloma (MM) characterized by the absence of monoclonal protein in the serum and/or urine. We look at the clinical and cytogenetic features of NSMM in this study.Patients and MethodsThis study evaluates a cohort of 30 patients with newly diagnosed NSMM seen at the Mayo Clinic, Rochester, MN, between 2008 and 2018 and treated with novel agent induction therapies. Survival outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test.ResultsThese patients with NSMM appear to have a large disease burden at diagnosis with a median bone marrow plasma cell percentage of 70% and more than one-half of all patients having Multiple Myeloma International Staging System Stage III disease. There was a higher preponderance for t(11;14) primary cytogenetic abnormality in this NSMM cohort, accounting for more than 50% of the cohort. Finally, the overall survival of this cohort appears to be slightly worse than a matched-control group of newly diagnosed patients with MM with secretory disease.ConclusionsFuture multi-institution studies confirming these above findings on this rare entity are warranted. 相似文献
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《Clinical Lymphoma, Myeloma & Leukemia》2020,20(3):174-183.e3
IntroductionThe therapeutic landscape for chronic lymphocytic leukemia (CLL) has significantly shifted with the approval of novel agents. Understanding current prognostic testing and treatment practices in this new era is critical. Beginning enrollment in 2015, informCLL is the first United States-based real-world, prospective, observational registry that initiated enrollment after approval of novel agents.Patients and MethodsEligible patients were age ≥ 18 years, started CLL treatment within 30 days of enrollment, and provided consent. For this planned interim analysis, treatments were classified into 5 groups: ibrutinib, chemoimmunotherapy, chemotherapy, immunotherapy, and other novel agents.ResultsFrequency of prognostic testing and treatment patterns are reported among 840 patients (459 previously untreated; 381 relapsed/refractory), enrolled largely (96%) from community practice settings. Testing for chromosomal abnormalities by fluorescence in situ hybridization, TP53 mutation, or IGHV mutation status occurred infrequently among all patients (31%, 11%, and 11%, respectively). Chemoimmunotherapy was the most common treatment in previously untreated patients (42%), whereas ibrutinib was the most common treatment among relapsed/refractory patients (51%). Of patients who tested positive for del(17p) or TP53 mutation, 34% and 26% received chemoimmunotherapy, respectively. Among patients who did not have fluorescence in situ hybridization or TP53 mutation testing prior to enrollment, 33% and 32% received chemoimmunotherapy, respectively.ConclusionOur findings indicate that prognostic testing rates were poor, and approximately one-third of high-risk patients (del[17p] and TP53) received chemoimmunotherapy, which is not aligned with current CLL treatment recommendations. This represents an opportunity to educate and alert health care professionals about the necessity of prognostic testing to guide optimal CLL treatment decisions. 相似文献
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Cinnie Yentia Soekojo Guo-miao Wang Yunxin Chen Joshua Casan Grace Wolyncewicz Adeline Lin Li Mei Poon Sanjay de Mel Liang Piu Koh Lip Kun Tan Melissa G. Ooi Chandramouli Nagarajan Yang Liu Yue-yun Lai Xiao-Jun Huang Andrew Spencer Sathish Kumar Gopalakrishnan Jin Lu Wee Joo Chng 《Clinical Lymphoma, Myeloma & Leukemia》2019,19(8):e470-e477
BackgroundThe Revised International Staging System (R-ISS) has been widely adopted to prognosticate multiple myeloma. As a result, the continued utility of conventional metaphase karyotyping has been called into question.Patients and MethodsA multi-center study for newly diagnosed patients with multiple myeloma who received novel agent(s) at induction was conducted. Conventional metaphase karyotype information was categorized based on ploidy. We evaluated the impact of ploidy on overall survival (OS) including multivariate analysis, taking into account the R-ISS stages, transplant status, age, and novel agent(s) used at induction. We also evaluated if it is possible to identify high-risk (HR) patients with conventional karyotyping when a fluorescence in situ hybridization analysis is not available. Results were validated in an independent cohort.ResultsThere were 308 patients evaluable. Ploidy significantly affected the OS of patients with R-ISS stage II, with non-hyperdiploid patients doing the worst. In the multivariate analysis, ploidy was significantly associated with OS. R-ISS stage II patients with or without non-hyperdiploid karyotype had significantly different survival. We replaced HR fluorescence in situ hybridization abnormalities with HR metaphase karyotypic abnormalities (non-hyperdiploid karyotype). When compared with R-ISS, there was a high level of concordance in HR patients identified using HR karyotypic abnormalities. These results were validated with an independent cohort of 375 patients.ConclusionConventional metaphase karyotyping is an independent prognostic factor even in the setting of R-ISS. 相似文献
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《Clinical Lymphoma, Myeloma & Leukemia》2017,17(9):545-554
In 2015, 2 monoclonal antibodies were approved for the treatment of relapsed or refractory multiple myeloma (RRMM), elotuzumab and daratumumab. Elotuzumab is a monoclonal IgG-κ antibody directed against SLAMF7 (signaling lymphocytic activation molecule F7), a cell surface receptor involved in natural killer cell activation. Daratumumab is a monoclonal IgG-κ antibody that binds to CD38, a transmembrane protein found on the surface of myeloma cells and responsible for cellular adhesion and ectoenzymatic activity. Both elotuzumab and daratumumab act through recruitment of the immune system to enhance cellular cytotoxicity directed against myeloma cells. Elotuzumab requires lenalidomide and dexamethasone combined to enhance progression-free survival in patients with RRMM, and daratumumab has both single-agent and combination activity with either lenalidomide or the proteasome inhibitor bortezomib in RRMM. The adverse effect profile of both agents mainly consists of allergic-type infusion reactions. Other considerations for monoclonal antibody use in the treatment of MM include the potential for interference in serum protein electrophoresis testing and cross-reactivity of daratumumab with CD38 present on red blood cells. In the present report, we discussed the clinical development of daratumumab and elotuzumab and newer immunologic approaches to the treatment of MM. 相似文献
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《Clinical genitourinary cancer》2022,20(2):114-122
IntroductionThe treatment landscape in locally advanced/unresectable or metastatic urothelial carcinoma (aUC) has evolved with the use of immune checkpoint inhibitors (ICIs) in the first line (1L) and platinum-refractory settings and with the recent approval of avelumab as 1L maintenance therapy for patients achieving disease control with platinum-containing regimens. Oncology provider perspectives and decision-making processes regarding aUC management, especially with the integration of recently approved strategies, such as maintenance therapy, have not been well-described.Patients and MethodsQualitative interview study with US oncologists and oncology nurses in academic and community settings in August 2020. Interviews explored decision-making around aUC 1L treatment eligibility determinants and selection, programmed cell death 1 ligand 1 (PD-L1) testing practices, and use of maintenance therapy. Thematic analysis was used to identify drivers of 1L treatment decisions.ResultsEighteen oncologists (women, 11%; >15 years in practice, 55%; academic, 39%) and 18 oncology nurses (women, 94%; >15 years in practice, 34%; academic, 50%) participated. Providers preferred platinum-based regimens in 1L setting and reserved 1L ICI monotherapy for frail patients. Providers preferred chemotherapy followed by switch maintenance ICI, as opposed to concurrent combination chemotherapy and ICI, followed by ICI as continuation maintenance. Decision-making was driven by need to adhere to treatment decision-making guidelines, characteristics of the patient, treatment efficacy and patient preference.ConclusionProviders adhered to guidelines and level I evidence in decision-making in the aUC 1L setting. Future studies should further evaluate barriers to the adoption of standard-of-care strategies and factors impacting decision-making in the real-world setting. 相似文献
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Although the increased risk of venous thrombotic events with thalidomide in multiple myeloma (MM) has been well described, an association with an increased risk of arterial events is less well appreciated. We describe 5 unusual arterial thromboses in patients with MM shortly after beginning thalidomide-based therapies. The cases are remarkable for a paucity of risk factors and short latency. We also review the literature on arterial thromboembolic events in patients taking thalidomide. Care should be taken in future trials to document arterial events with both thalidomide and lenalidomide. 相似文献
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The VAD regimen is effective in the treatment of resistant and relapsing multiple myeloma. In the original VAD regimen, vincristine (V) and doxorubicin (A) are given as continuous infusions together with peroral dexamethasone (D). For practical reasons, we have shortened the infusion times: 8 hours for vincristine and 1 hour for doxorubicin. In this retrospective analysis, we have compared the efficacy and toxicity of the original and modified VAD protocols in the treatment of myeloma patients at our institution. Of the 31 consecutive patients with myeloma, primarily or secondarily resistant to alkylating agents, 16 were treated by the original and 15 by the modified VAD protocol. We found no significant difference in the response rates (good responses 31% and 20% respectively), survival times (17 and 9 months respectively) or toxicity between the two protocols. VAD may well be modified so as to consist of short infusions of V and A. The overall efficacy of the traditional and modified regimens is, however, rather unsatisfactory in patients with advanced myeloma. 相似文献
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Krystal Bergin Cameron Wellard Elizabeth Moore Zoe McQuilten Hilary Blacklock Simon J. Harrison P. Joy Ho Tracy King Hang Quach Peter Mollee Patricia Walker Erica Wood Andrew Spencer 《Clinical Lymphoma, Myeloma & Leukemia》2021,21(6):e510-e520
BackgroundReal-world multiple myeloma (MM) data are scarce, with most data originating from clinical trials. The Myeloma and Related Diseases Registry (MRDR) is a prospective clinical-quality registry of newly diagnosed cases of plasma cell disorders established in 2012 and operating at 44 sites in Australia and New Zealand as of April 2020.MethodsWe reviewed all patients enrolled onto the MRDR between June 2012 and April 2020. Baseline characteristics, treatment, and outcome data were reviewed for MM patients with comparisons made by chi-square tests (categorical variables) and rank sum tests (continuous variables). Kaplan-Meier analysis was used to estimate progression-free survival and overall survival (OS).ResultsAs of April 2020, a total of 2405 MM patients were enrolled (median age, 67 years, with 40% aged > 70 years). High-risk features were present in 13% to 31% of patients: fluorescence in-situ hybridization (FISH) ≥ 1 of t(4;14), t(14;16), or del(17p) 18%, International Staging System (ISS)-3 31%, and Revised ISS (R-ISS)-3 13%. Cytogenetic/FISH analyses were performed in 50% and 68% of patients, respectively, with an abnormal karyotype result in 34%. Bortezomib-containing therapy was the most common first-line therapy (79.3%, n = 1706). Patients not receiving bortezomib were older (median age, 76 vs 65 years, P < .001) with inferior performance status (Eastern Cooperative Oncology Group performance status ≥ 2, 41% vs 18%, P < .001). Median progression-free survival and OS were 30.8 and 65.8 months, respectively. Younger patients had superior OS (76.3 vs 46.7 months, P < .001, < 70 and ≥ 70 years, respectively). R-ISS score was available in 50.7% (n = 1220) of patients, and higher R-ISS was associated with inferior OS (R-ISS-1 vs R-ISS-2 vs R-ISS-3: not reached vs 68.1 months vs 33.2 months, respectively, P < .001).ConclusionClinical registries provide a more complete picture of MM diagnosis and treatment, and highlight the challenges of adhering to best practices in a real-world context. 相似文献
14.
《Journal of thoracic oncology》2020,15(6):914-947
In the past 10 years, a deeper understanding of the immune landscape of cancers, including immune evasion processes, has allowed the development of a new class of agents. The reactivation of host antitumor immune response offers the potential for long-term survival benefit in a portion of patients with thoracic malignancies.The advent of programmed cell death protein 1/programmed death ligand-1 immune checkpoint inhibitors (ICIs), both as single agents and in combination with chemotherapy, and more recently, the combination of ICI, anti–programmed cell death protein 1, and anticytotoxic T-lymphocyte antigen 4 antibody, have led to breakthrough therapeutic advances for patients with advanced NSCLC, and to a lesser extent, patients with SCLC. Encouraging activity has recently emerged in pretreated patients with thymic carcinoma (TC). Conversely, in malignant pleural mesothelioma, pivotal positive signs of activity have not been fully confirmed in randomized trials. The additive effects of chemoradiation and immunotherapy suggested intriguing potential for therapeutic synergy with combination strategies. This has led to the introduction of ICI consolidation therapy in stage III NSCLC, creating a platform for future therapeutic developments in earlier-stage disease. Despite the definitive clinical benefit observed with ICI, primary and acquired resistance represent well-known biological phenomena, which may affect the therapeutic efficacy of these agents.The development of innovative strategies to overcome ICI resistance, standardization of new patterns of ICI progression, identification of predictive biomarkers of response, optimal treatment duration, and characterization of ICI efficacy in special populations, represent crucial issues to be adequately addressed, with the aim of improving the therapeutic benefit of ICI in patients with thoracic malignancies.In this article, an international panel of experts in the field of thoracic malignancies discussed these topics, evaluating currently available scientific evidence, with the final aim of providing clinical recommendations, which may guide oncologists in their current practice and elucidate future treatment strategies and research priorities. 相似文献
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Multidrug resistance, mediated by the P-glycoprotein 170 transport pump, is a serious problem in multiple myeloma. In this review we discuss the expression of P-gp as a differentiation antigen on normal T and B lymphocytes. In myeloma, circulating presumptively malignant B cells express P-gp prior to chemotherapy. A variety of evidence characterizes these circulating B cells as members of the malignant clone in myeloma, including the demonstration that they share immunoglobulin heavy chain (IgH) rearrangements with bone marrow plasma cells, and their extensive DNA aneuploidy. In some patients the only components of the clonal populations that express P-gp are the circulating B cells suggesting that they represent a reservoir of multidrug resistant cells that maintain malignant growth and spread in myeloma. We speculate that exposure to chemotherapy alters clonal homeostasis and exerts positive selection pressure on generative components of the myeloma clone. Thus the possibility exists that chemotherapy perpetuates rather than eradicates myeloma stem cells. P-gp is detectable on bone marrow plasma cells in myeloma but appears to be in an inactive form that is unable to mediate efflux of marker dyes. A similar phenomenon is seen for normal human monocytes which have surface P-gp but lack any functional export of P-gp substrates. P-gp appears to vary depending in a cell-type specific manner suggesting that it may be feasible to design inhibitors of P-gp which selectively block P-gp export by malignant cells and spare the function of P-gp on normal tissue, including lymphocytes and normal hematopoietic stem cells. 相似文献
17.
Treatment deintensification in human papillomavirus‐positive oropharynx cancer: Outcomes from the National Cancer Data Base 下载免费PDF全文
Shayan Cheraghlou BA Phoebe K. Yu MD Michael D. Otremba MD Henry S. Park MD MPH Aarti Bhatia MD MPH Cheryl K. Zogg MSPH MHS Saral Mehra MD MBA Wendell G. Yarbrough MD Benjamin L. Judson MD 《Cancer》2018,124(4):717-726
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Arleigh McCurdy Christopher P. Venner Esther Masih-Khan Martha Louzada Richard LeBlanc Michael Sebag Kevin Song Victor H. Jimenez-Zepeda Rami Kotb Moustafa Kardjadj Hira Mian Darrell White Julie Stakiw Muhammad Aslam Anthony Reiman Engin Gul Donna Reece 《Current oncology (Toronto, Ont.)》2022,29(3):1575
The treatment of multiple myeloma has dramatically improved due to the availability of novel therapies that are highly effective and are quickly moving into first-line therapy. The Canadian Agency for Drugs and Technologies in Health (CADTH) recently recommended that patients who receive daratumumab should only be eligible to receive either carfilzomib or pomalidomide but not both, for relapsed MM. In order to assess the efficacy of these two agents in the relapsed setting, we utilized our national myeloma database. A total of 121 patients were reviewed, 49 patients received CAR- before POM-based (CAR-POM), and 73 patients received POM- before CAR-based (POM-CAR) therapy. In the groups selected, the median PFS was 4.93 months (95% CI, 2.76–7.07) and 5.36 months (95% CI, 3.75–6.94) for CAR-POM and POM-CAR, respectively. The median OS for patients treated with CAR-POM was 11.01 months (95% CI, 4.50–19.13), and for patients treated with POM-CAR the median OS was 10.98 months (95% CI, 8.98–19.17). In this real-world observational study, we demonstrated that both CAR- and POM-based therapies, irrespective of the order in which they were used, were effective treatment options for patients with advanced relapsed MM. 相似文献
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Treatment and outcomes of melanoma in Asia: Results from the National Cancer Centre Singapore 下载免费PDF全文
Sze Huey Tan Grace Yong Alisa Noor Hidayah Sairi Khee Chee Soo Johnny Ong Claramae Chia Grace Tan Henry Soeharno Mann Hong Tan Michelle Chan Selvarajan Sathiyamoorthy Kesavan Sittampalam Jonathan Teh Francis Chin Vijay Sethi Melissa Teo Richard Quek Mohamad Farid 《Asia-Pacific Journal of Clinical Oncology》2018,14(2):e95-e102