Bruce D Cheson

Georgetown University, Washington, Washington, D.C., United States

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Publications (411)2760.39 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The International Prognostic Score (IPS-7) is the most commonly used risk stratification tool for advanced Hodgkin lymphoma (HL), however recent studies suggest the IPS-7 is less discriminating due to improved outcomes with contemporary therapy. We evaluated the seven variables for IPS-7 recorded at study entry for 854 patients enrolled on Eastern Cooperative Oncology Group 2496 trial. Univariate and multivariate Cox models were used to assess their prognostic ability for freedom from progression (FFP) and overall survival (OS). The IPS-7 remained prognostic however its prognostic range has narrowed. On multivariate analysis, two factors (age, stage) remained significant for FFP and three factors (age, stage, haemoglobin level) for OS. An alternative prognostic index, the IPS-3, was constructed using age, stage and haemoglobin level, which provided four distinct risk groups [FFP (P = 0·0001) and OS (P < 0·0001)]. IPS-3 outperformed the IPS-7 on risk prediction for both FFP and OS by model fit and discrimination criteria. Using reclassification calibration, 18% of IPS-7 low risk patients were re-classified as intermediate risk and 13% of IPS-7 intermediate risk patients as low risk. For patients with advanced HL, the IPS-3 may provide a simpler and more accurate framework for risk assessment in the modern era. Validation of these findings in other large data sets is planned.
    British Journal of Haematology 09/2015; DOI:10.1111/bjh.13634 · 4.71 Impact Factor
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    ABSTRACT: Lenalidomide and rituximab (LR) are active agents in follicular lymphoma (FL). Combination regimens have not been previously assessed in randomized studies. The Cancer and Leukemia Group B (Alliance) 50401 trial is a randomized phase II trial studying rituximab (375 mg/m(2) weekly for 4 weeks), lenalidomide (15 mg per day on days 1 to 21, followed by 7 days of rest, in cycle 1 and then 20 mg per day on days 1 to 21, followed by 7 days of rest, in cycles 2 to 12), or LR. The rituximab-alone arm was discontinued as a result of poor accrual. Eligibility included recurrent FL and prior rituximab with time to progression of ≥ 6 months from last dose. Aspirin or heparin was recommended for patients at high thrombosis risk. Ninety-one patients (lenalidomide, n = 45; LR, n = 46) received treatment; median age was 63 years (range, 34 to 89 years), and 58% were intermediate or high risk according to the Follicular Lymphoma International Prognostic Index. In the lenalidomide and LR arms, grade 3 to 4 adverse events occurred in 58% and 53% of patients, with 9% and 11% of patients experiencing grade 4 toxicity, respectively; grade 3 to 4 adverse events included neutropenia (16% v 20%, respectively), fatigue (9% v 13%, respectively), and thrombosis (16% [n = 7] v 4% [n = 2], respectively; P = .157). Thirty-six percent of lenalidomide patients and 63% of LR patients completed 12 cycles. Lenalidomide alone was associated with more treatment failures, with 22% of patients discontinuing treatment as a result of adverse events. Dose-intensity exceeded 80% in both arms. Overall response rate was 53% (20% complete response) and 76% (39% complete response) for lenalidomide alone and LR, respectively (P = .029). At the median follow-up of 2.5 years, median time to progression was 1.1 year for lenalidomide alone and 2 years for LR (P = .0023). LR is more active than lenalidomide alone in recurrent FL with similar toxicity, warranting further study in B-cell non-Hodgkin lymphoma as a platform for addition of novel agents. © 2015 by American Society of Clinical Oncology.
    Journal of Clinical Oncology 08/2015; 30. DOI:10.1200/JCO.2014.59.9258 · 18.43 Impact Factor
  • Journal of Clinical Oncology 08/2015; DOI:10.1200/JCO.2015.63.2125 · 18.43 Impact Factor
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    Mayo Clinic Proceedings 07/2015; 90(8). DOI:10.1016/j.mayocp.2015.06.001 · 6.26 Impact Factor
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    ABSTRACT: Aurora A kinase (AAK) is upregulated in highly proliferative lymphomas, suggesting its potential as a therapeutic target. Alisertib is a novel oral AAK inhibitor without adverse safety signals in early-phase studies that demonstrated preliminary activity in T-cell lymphoma. This phase II study was conducted to further investigate the efficacy of alisertib in relapsed or refractory peripheral T-cell non-Hodgkin lymphoma (PTCL). Eligible patients with histologically confirmed relapsed/refractory PTCL or transformed Mycosis fungoides (tMF) received alisertib 50 mg twice a day for 7 days on 21-day cycles. Of 37 eligible patients, the histologic subtypes enrolled included PTCL not otherwise specified (n = 13), angioimmunoblastic T-cell lymphoma (n = 9), tMF (n = 7), adult T-cell lymphoma/leukemia (n = 4), anaplastic large-cell lymphoma (n = 2), and extranodal natural killer/T-cell lymphoma (n = 2). Grade 3 and 4 adverse events in ≥ 5% of patients included neutropenia (32%), anemia (30%), thrombocytopenia (24%), febrile neutropenia (14%), mucositis (11%), and rash (5%). Treatment was discontinued most commonly for disease progression. Among the PTCL subtypes, the overall response rate was 30%, whereas no responses were observed in tMF. Aurora B kinase was more commonly overexpressed than AAK in tumor specimens. Analysis of AAK, Aurora B kinase, MYC, BCL-2, phosphatidylinositol 3-kinase γ, and Notch1 expression revealed no association with response. Alisertib has antitumor activity in PTCL, including heavily pretreated patients. These promising results are being further investigated in an ongoing international, randomized phase III trial comparing alisertib with investigator's choice in PTCL. © 2015 by American Society of Clinical Oncology.
    Journal of Clinical Oncology 06/2015; 33(21). DOI:10.1200/JCO.2014.60.6327 · 18.43 Impact Factor
  • Bruce D Cheson
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    ABSTRACT: Standardized response criteria for lymphoma are critical for the evaluation of new therapies. Widely adopted recommendations, most recently the Lugano classification, have been developed primarily for assessment of conventional chemotherapeutic regimens. More recently, several classes of drugs, including immunomodulatory agents, B cell receptor pathway targeting kinases, and checkpoint (PD-1, PDL-1) inhibitors have demonstrated impressive activity in a broad range of histologies. However, they may be associated with features during treatment suggestive of progressive disease despite clinical benefit. Immune response criteria have been proposed for solid tumors, and a modification is needed to be more applicable to lymphomas. Following treatment, conservative use of imaging is recommended based on clinical indications. As newer targeted agents with unique mechanisms of action are developed, current response and follow-up criteria must be made sufficiently flexible for optimal evaluation.
    Current Oncology Reports 06/2015; 17(6):452. DOI:10.1007/s11912-015-0452-2 · 2.89 Impact Factor
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    ABSTRACT: The phase III North American Intergroup E2496 Trial (Combination Chemotherapy With or Without Radiation Therapy in Treating Patients With Hodgkin's Lymphoma) compared doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) with mechlorethamine, doxorubicin, vincristine, bleomycin, vinblastine, etoposide, and prednisone (Stanford V). We report results of a planned subgroup analysis in patients with stage I or II bulky mediastinal Hodgkin lymphoma (HL). Patients were randomly assigned to six to eight cycles of ABVD every 28 days or Stanford V once per week for 12 weeks. Two to 3 weeks after completion of chemotherapy, all patients received 36 Gy of modified involved field radiotherapy (IFRT) to the mediastinum, hila, and supraclavicular regions. Patients on the Stanford V arm received IFRT to additional sites ≥ 5 cm at diagnosis. Primary end points were failure-free survival (FFS) and overall survival (OS). Of 794 eligible patients, 264 had stage I or II bulky disease, 135 received ABVD, and 129 received Stanford V. Patient characteristics were matched. The overall response rate was 83% with ABVD and 88% with Stanford V. At a median follow-up of 6.5 years, the study excluded a difference of more than 21% in 5-year FFS and more than 16% in 5-year OS between ABVD and Stanford V (5-year FFS: 85% v 79%; HR, 0.68; 95% CI, 0.37 to 1.25; P = .22; 5-year OS: 96% v 92%; HR, 0.49; 95% CI, 0.16 to 1.47; P = .19). In-field relapses occurred in < 10% of the patients in each arm. For patients with stage I or II bulky mediastinal HL, no substantial statistically significant differences were detected between the two regimens, although power was limited. To the best of our knowledge, this is the first prospective trial reporting outcomes specific to this subgroup, and it sets a benchmark for comparison of ongoing and future studies. © 2015 by American Society of Clinical Oncology.
    Journal of Clinical Oncology 04/2015; 33(17). DOI:10.1200/JCO.2014.57.8138 · 18.43 Impact Factor
  • Bruce D Cheson
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    ABSTRACT: Staging and response criteria were initially developed for Hodgkin lymphoma (HL) over 60 years ago, but not until 1999 were response criteria published for non-HL (NHL). Revisions to these criteria for both NHL and HL were published in 2007 by an international working group, incorporating PET for response assessment, and were widely adopted. After years of experience with these criteria, a workshop including representatives of most major international lymphoma cooperative groups and cancer centers was held at the 11th International Conference on Malignant Lymphoma (ICML) in June, 2011 to determine what changes were needed. An Imaging Task Force was created to update the relevance of existing imaging for staging, reassess the role of interim PET-CT, standardize PET-CT reporting, and to evaluate the potential prognostic value of quantitative analyses using PET and CT. A clinical task force was charged with assessing the potential of PET-CT to modify initial staging. A subsequent workshop was help at ICML-12, June 2013. Conclusions included: PET-CT should now be used to stage FDG-avid lymphomas; for others, CT will define stage. Whereas Ann Arbor classification will still be used for disease localization, patients should be treated as limited disease [I (E), II (E)], or extensive disease [III-IV (E)], directed by prognostic and risk factors. Since symptom designation A and B are frequently neither recorded nor accurate, and are not prognostic in most widely used prognostic indices for HL or the various types of NHL, these designations need only be applied to the limited clinical situations where they impact treatment decisions (e.g., stage II HL). PET-CT can replace the bone marrow biopsy (BMBx) for HL. A positive PET of bone or bone marrow is adequate to designate advanced stage in DLBCL. However, BMBx can be considered in DLBCL with no PET evidence of BM involvement, if identification of discordant histology is relevant for patient management, or if the results would alter treatment. BMBx remains recommended for staging of other histologies, primarily if it will impact therapy. PET-CT will be used to assess response in FDG-avid histologies using the 5-point scale, and included in new PET-based response criteria, but CT should be used in non-avid histologies. The definition of PD can be based on a single node, but must consider the potential for flare reactions seen early in treatment with newer targeted agents which can mimic disease progression. Routine surveillance scans are strongly discouraged, and the number of scans should be minimized in practice and in clinical trials, when not a direct study question. Hopefully, these recommendations will improve the conduct of clinical trials and patient management.
    03/2015; 4(1):5. DOI:10.3978/j.issn.2304-3865.2014.11.03
  • Bruce D. Cheson · Jeanette Crawford
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    ABSTRACT: Many patients with non-Hodgkin (NHL) or Hodgkin lymphoma (HL) relapse or are refractory to initial therapy and require additional options. Bendamustine (B), lenalidomide (L) and rituximab (R) each have activity in this setting. This study was performed to determine the safety of BLR and its optimal phase II dose. Patients with NHL or HL failing standard therapies received B (90 mg/m(2) days 1, 2 every 28 days), and L (escalating from 5 mg 21/28 days) for six cycles, followed by 6 months of L. At the highest dose R 375 mg/m(2) on day one of each cycle was added for patients with B-NHL. Histologies included diffuse large B-cell lymphoma (DLBCL, 11), marginal zone lymphoma (3), HL (2), and one each of transformed follicular lymphoma, Sézary syndrome, Waldenström macroglobulinaemia and mantle cell lymphoma. Neutropenia was the most common grade 3 and 4 toxicity, but no maximum tolerated dose was identified. Of 20 patients, seven responded (35%), including four complete remissions, with five unmaintained responses from 28+ to 37+ months, including 2 DLBCL. BR with 20 mg l at, 21/28 days achieved durable responses; however, in light of its modest activity, and the availability of newer targeted therapies, the future of BLR is uncertain. © 2015 John Wiley & Sons Ltd.
    British Journal of Haematology 03/2015; 169(4). DOI:10.1111/bjh.13321 · 4.71 Impact Factor
  • Bruce D Cheson · Jun Zhu
    03/2015; 4(1):2. DOI:10.3978/j.issn.2304-3865.2015.03.06
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    ABSTRACT: Antibody drug conjugates (ADCs), in which cytotoxic drugs are linked to antibodies targeting antigens on tumor cells, represent promising novel agents for the treatment of malignant lymphomas. Pinatuzumab vedotin is an anti-CD22 ADC and polatuzumab vedotin an anti-CD79B ADC that are both linked to the microtubule-disrupting agent monomethyl auristatin E (MMAE). In the present study, we analyzed the activity of these agents in different molecular subtypes of diffuse large B-cell lymphoma (DLBCL) both in vitro and in early clinical trials. Both anti-CD22-MMAE and anti-CD79B-MMAE were highly active and induced cell death in the vast majority of activated B-cell-like (ABC) and germinal center B-cell-like (GCB) DLBCL cell lines. Similarly, both agents induced cytotoxicity in models with and without mutations in the signaling molecule CD79B. In line with these observations, relapsed and refractory DLBCL patients of both subtypes responded to these agents. Importantly, a strong correlation between CD22 and CD79B expression in vitro and in vivo was not detectable, indicating that patients should not be excluded from anti-CD22-MMAE or anti-CD79B-MMAE treatment due to low target expression. In summary, these studies suggest that pinatuzumab vedotin and polatuzumab vedotin are active agents for the treatment of patients with different subtypes of DLBCL.Leukemia accepted article preview online, 24 February 2015. doi:10.1038/leu.2015.48.
    Leukemia 02/2015; 29(7). DOI:10.1038/leu.2015.48 · 10.43 Impact Factor
  • Source
    Journal of Clinical Oncology 02/2015; 33(10). DOI:10.1200/JCO.2014.59.9373 · 18.43 Impact Factor
  • Bruce D Cheson
    Clinical advances in hematology & oncology: H&O 02/2015; 13(1):12.
  • Chaitra Ujjani · Bruce D Cheson
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    ABSTRACT: Introduction: Follicular lymphoma, the most common of the indolent non-Hodgkin lymphomas, exhibits a highly variable clinical course. The disease is characterized by a high response rate to therapy, but due to repeated relapses additional treatment options are necessary. Areas covered: The rediscovered chemotherapeutic agent, bendamustine, has demonstrated remarkable efficacy and tolerability when paired with rituximab and has been established as a front-line regimen. More recently, a number of new targeted therapies have been developed, directed against intrinsic drivers of malignant B-cell proliferation and survival, and extrinsic factors such as the tumor microenvironment and escape from the immune response. For the first time, a targeted oral agent, idelalisib, is now FDA approved for the treatment of this disease. Expert opinion: The promise of these new therapies has enabled us to move forward with multi-targeted biologic regimens and toward a future of individualized treatment without traditional chemotherapy.
    Expert Opinion on Orphan Drugs 02/2015; 3(2). DOI:10.1517/21678707.2015.1011123 · 0.53 Impact Factor
  • Bruce D Cheson
    Clinical advances in hematology & oncology: H&O 02/2015; 13(2):78.
  • Source
    01/2015; 3(1):2. DOI:10.7243/2052-434X-3-2
  • Bruce D Cheson
    Clinical advances in hematology & oncology: H&O 12/2014; 12(12):797.
  • Bruce D Cheson
    Clinical advances in hematology & oncology: H&O 11/2014; 12(11):718.
  • Bruce D Cheson
  • Source
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    ABSTRACT: Ixazomib is an investigational proteasome inhibitor that has shown preclinical activity in lymphoma models. This phase 1 study assessed the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics and preliminary activity of intravenous (IV) ixazomib in relapsed/refractory lymphoma patients who had received ⩾2 prior therapies. Thirty patients with a range of histologies received ixazomib 0.125-3.11 mg/m(2) on days 1, 8 and 15 of 28-day cycles. Patients received a median of two cycles (range 1-36). MTD was determined to be 2.34 mg/m(2). Most common drug-related adverse events (AEs) included fatigue (43%), diarrhea (33%), nausea, vomiting and thrombocytopenia (each 27%). Drug-related grade ⩾3 AEs included neutropenia (20%), thrombocytopenia (13%) and diarrhea (10%). Drug-related peripheral neuropathy occurred in four (13%) patients; no grade ⩾3 events were reported. Plasma exposure increased dose proportionally from 0.5-3.11 mg/m(2); terminal half-life was 4-12 days after multiple dosing. Of 26 evaluable patients, five achieved responses: 4/11 follicular lymphoma patients (one complete and three partial responses) and 1/4 peripheral T-cell lymphoma patients (partial response). Sustained responses were observed with ⩾32 cycles of treatment in two heavily pretreated follicular lymphoma patients. Results suggest weekly IV ixazomib is generally well tolerated and may be clinically active in relapsed/refractory lymphoma.
    Blood Cancer Journal 10/2014; 4(10):e251. DOI:10.1038/bcj.2014.71 · 3.47 Impact Factor

Publication Stats

19k Citations
2,760.39 Total Impact Points


  • 2003–2015
    • Georgetown University
      • Division of Hematology and Oncology
      Washington, Washington, D.C., United States
  • 2013
    • American University Washington D.C.
      Washington, Washington, D.C., United States
  • 2012
    • University of Chicago
      Chicago, Illinois, United States
    • BC Cancer Research Centre
      Vancouver, British Columbia, Canada
  • 2011
    • Washington Hospital Center
      Washington, Washington, D.C., United States
  • 2010
    • University of Wisconsin–Madison
      • Department of Medicine
      Madison, Wisconsin, United States
  • 2008–2010
    • The Harvard Drug Group
      Ливония, Michigan, United States
    • Roswell Park Cancer Institute
      • Department of Medicine
      Buffalo, New York, United States
    • University of Rochester
      • James P. Wilmot Cancer Center
      Rochester, NY, United States
  • 2002–2010
    • University of Cologne
      • Department of Internal Medicine
      Köln, North Rhine-Westphalia, Germany
  • 2009
    • Duke University
      Durham, North Carolina, United States
  • 1987–2007
    • National Cancer Institute (USA)
      • Cancer Therapy Evaluation Program
      Maryland, United States
  • 2006
    • University of California, San Diego
      • Department of Medicine
      San Diego, California, United States
    • Radboud University Nijmegen
      Nymegen, Gelderland, Netherlands
    • Washington DC VA Medical Center
      Washington, Washington, D.C., United States
  • 2005–2006
    • University of Iowa
      • Department of Radiology
      Iowa City, IA, United States
    • University of Nebraska at Omaha
      Omaha, Nebraska, United States
    • Stanford University
      Palo Alto, California, United States
  • 2004
    • Universität Ulm
      Ulm, Baden-Württemberg, Germany
  • 1998–2002
    • National Institutes of Health
      • Center for Cancer Research
      베서스다, Maryland, United States
  • 2000
    • Massachusetts General Hospital
      Boston, Massachusetts, United States
  • 1987–1993
    • The EMMES Corporation
      Maryland, United States
  • 1980–1987
    • University of Utah
      • • Department of Biology
      • • School of Medicine
      • • Department of Internal Medicine
      Salt Lake City, UT, United States