Revised Response Criteria for Malignant Lymphomas From the Members of the International Harmonization Project (IHP) of the Competence Network Malignant Lymphoma, Represented by:.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 18-18 ◽  
Author(s):  
Bruce D. Cheson ◽  
Beate Pfistner ◽  
Malik E. Juweid ◽  
Lena Specht ◽  
Steven T. Rosen ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clin Oncol ◽  
Residual Disease ◽  
Response Assessment ◽  
Study Groups ◽  
Response Criteria ◽  
Regulatory Agencies ◽  
Disease Response ◽  
Hodgkin's Lymphomas ◽  
Pet Scans

Abstract Standardized response criteria are essential for interpretation of clinical data, comparisons among clinical trials, development of new therapies, and approval of agents by regulatory agencies. In 1999, an International Working Group (IWG) developed recommendations for response assessment for non-Hodgkin’s lymphomas (NHL) that were adopted internationally by study groups and regulatory agencies and, subsequently, by clinical trials groups for Hodgkin lymphoma (HL) as well (Cheson et al, J Clin Oncol, 17:1244, 1999). Since their publication, several observations compelled a reassessment and, ultimately, revision of those guidelines, e.g., the availability of FDG-PET scans, new insights into lymphoma pathology and biology, the failure of the IWG guidelines to include HL and extranodal NHL, and features of the original guidelines that were found to be unclear as they were implemented into clinical trials. Most notable of these was the interpretation of the response category of Complete Remission unconfirmed (CRu). In the context of the IHP, a group of international lymphoma investigators with expertise in medical hematology/oncology, radiation oncology, nuclear medicine and imaging, pathology, biostatistics, and pediatrics were convened to revise the IWG guidelines. Committees focused on Response Criteria, Pathology/Biology, Endpoints, and Clinical Features, and discussions were initiated to undertake a major revision of the IWG guidelines. The important modifications that will be presented included, but were not limited to, integration of PET according to recent data (Juweid et al, J Clin Oncol, 23:4652, 2005), to facilitate the distinction between persistent tumor and scar/fibrosis, virtually eliminate the designation of CRu, and improve prediction of outcome. Guidelines were provided for the specific indications where this test can be currently recommended. Other proposals involved the role of flow cytometry and assessment of minimal residual disease. Response criteria for extranodal sites were also incorporated. Adoption of these revised guidelines by study groups will further improve the conduct and interpretation of clinical trials leading to more effective therapies for patients with lymphomas.

scholarly journals Tumor Reduction in Multiple Myeloma: New Concepts for New Therapeutics

2022 ◽  
Vol 11 ◽  
Author(s):  
Rafael Alonso ◽  
Juan José Lahuerta
Keyword(s):  
Multiple Myeloma ◽  
Residual Disease ◽  
Imaging Techniques ◽  
Prognostic Significance ◽  
Response Assessment ◽  
Tumor Burden ◽  
Response Criteria ◽  
Disease Response ◽  
Tumor Reduction ◽  
Novel Therapeutic Strategies

The development of new resources for a more accurate diagnosis and response assessment in multiple myeloma has been a long process for decades, mainly since the middle of the 20th century. During this time, the succession of technical advances has run parallel to the better knowledge of disease biology and the availability of novel therapeutic strategies. The cornerstone of standardized criteria to uniformly evaluate the disease response in myeloma dates back to the 1990s when the key role of complete remission was established. Since then, different updates have been implemented according to available scientific evidences not always without certain controversies. The progressive improvements in survival results of myeloma patients and the growing quality of responses due to the novel therapies have led to the need of developing new tools for better monitoring of tumor burden. In this way, the concept of minimal residual disease and its key value based on the prognostic significance and the clinical relevance has been consolidated during the last years, overcoming the value of conventional response criteria or classical adverse prognosis markers. Nevertheless, its precise role in the clinical management of myeloma patients to detect early treatment failure and trigger early rescue strategies is still pending to be defined. In this review, we revisit the major milestones in the understanding of tumor reduction in multiple myeloma until the most recent imaging techniques or liquid biopsy approaches, including a critical view of conventional response criteria, whose backbone has remained unchanged during the last 20 years.

scholarly journals Proposals for revised IWG 2018 hematological response criteria in patients with MDS included in clinical trials

Blood ◽  
2019 ◽  
Vol 133 (10) ◽  
pp. 1020-1030 ◽  
Author(s):  
U. Platzbecker ◽  
P. Fenaux ◽  
L. Adès ◽  
A. Giagounidis ◽  
V. Santini ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Myelodysplastic Syndromes ◽  
Working Group ◽  
Lower Risk ◽  
Response Assessment ◽  
Response To Treatment ◽  
Response Criteria ◽  
Patient Response ◽  
Erythroid Response ◽  
Clinical Responses

Abstract The heterogeneity of myelodysplastic syndromes (MDSs) has made evaluating patient response to treatment challenging. In 2006, the International Working Group (IWG) proposed a revision to previously published standardized response criteria (IWG 2000) for uniformly evaluating clinical responses in MDSs. These IWG 2006 criteria have been used prospectively in many clinical trials in MDSs, but proved challenging in several of them, especially for the evaluation of erythroid response. In this report, we provide rationale for modifications (IWG 2018) of these recommendations, mainly for “hematological improvement” criteria used for lower-risk MDSs, based on recent practical and reported experience in clinical trials. Most suggestions relate to erythroid response assessment, which are refined in an overall more stringent manner. Two major proposed changes are the differentiation between “procedures” and “criteria” for hematologic improvement–erythroid assessment and a new categorization of transfusion-burden subgroups.

scholarly journals Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute–Working Group 1996 guidelines

Blood ◽  
2008 ◽  
Vol 111 (12) ◽  
pp. 5446-5456 ◽  
Author(s):  
Michael Hallek ◽  
Bruce D. Cheson ◽  
Daniel Catovsky ◽  
Federico Caligaris-Cappio ◽  
Guillaume Dighiero ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Chronic Lymphocytic Leukemia ◽  
National Cancer Institute ◽  
Working Group ◽  
International Workshop ◽  
Treatment Options ◽  
Response Assessment ◽  
Lymphocytic Leukemia ◽  
Regulatory Agencies ◽  
Criteria For Diagnosis

Abstract Standardized criteria for diagnosis and response assessment are needed to interpret and compare clinical trials and for approval of new therapeutic agents by regulatory agencies. Therefore, a National Cancer Institute–sponsored Working Group (NCI-WG) on chronic lymphocytic leukemia (CLL) published guidelines for the design and conduct of clinical trials for patients with CLL in 1988, which were updated in 1996. During the past decade, considerable progress has been achieved in defining new prognostic markers, diagnostic parameters, and treatment options. This prompted the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) to provide updated recommendations for the management of CLL in clinical trials and general practice.

Use of Free Light Measurements in Clinical Trials of Novel Agents in Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3584-3584
Author(s):  
Amitabha Mazumder ◽  
Sundar Jagannath
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Clinical Trials ◽  
Warning System ◽  
Complete Response ◽  
Threshold Level ◽  
Novel Agents ◽  
Response Criteria ◽  
Disease Response ◽  
M Proteins

The free light assay has been reported to be valuable in monitoring patients with non-secretory multiple myeloma (MM). Furthermore, because of its short half-life, it may be useful even in patients who produce intact M-proteins. Recently, FLC has also been included in a revised response criteria for MM (BGM Durie et al International uniform response criteria for multiple myeloma. Leukemia, 7/20/06, online, 1–7,2006). We decided to study the applicability of the measurement of free light chains (FLC) in patients who were treated on clinical trials at our center with novel agents such as bortezomib and lenalidomide. We followed 21 patients with non- or hyposecretory MM with FLC measurements. These patients did not have measurable intact M-proteins and had only small amount of urine total protein (UTP) or Bence-Jones protein (BJP) present (< 0.3 mg/24hours). In 7 patients on bortezomib trials and 6 patients on lenalidomide trials, the involved FLC decreased by > 50% without the ability to detect any change in the UTP or BJP. The disease response seen was confirmed by bone marrow exams when available. Conversely, in 3 patients on each of the 2 agents, there was progression (> 25% increase) in the involved FLC without measurable increase in the small amount of UTP or BJP present, confirmed by either bone marrow or skeletal progression. Thus, in these patients, the FLC provided the only convenient means of monitoring. In 14 and 12 patients on bortezomib and lenalidomide respectively who had measurable UTP and BJP or serum M-proteins, there was a > 50% decrease in the FLC upto 8 weeks before any significant changes were seen in the urine protein measures or in serum M-proteins. Furthermore, the decrease continued after the UTP and BJP had reached a low possibly threshold level. In fact, 1 complete response on bortezomib was seen, confirmed by bone marrow studies, even with residual UTP (possibly due to bisphosphonate effect). Conversely, in 11 and 10 patients on bortezomib and lenalidomide respectively with measurable UTP and BJP or serum M, the increase in the involved FLC preceded progression in the parameters by upto 6 weeks. Thus, in these patients, the FLC provided an early warning system for their response or lack thereof. With respect to the criteria included in the reference cited above, the difference between the FLC was less meaningful in those patients with renal insufficiency, since both are significantly elevated in this state. The ratio however was the least meaningful since it was either 0 or infinite for a long time period depending upon which FLC was involved. Thus, FLC measurements are useful for monitoring patients who might not otherwise be eligible or benefit from clinical trials of novel agents. It can also serve as a early harbinger of response or progression. However, the limitations of the assay with respect to ratios and differences need to noted.

Correlation of minimal residual disease negativity (MRD-) with prognosis in high-risk myeloma (HRM).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8024-8024
Author(s):  
Chutima Kunacheewa ◽  
Krina K. Patel ◽  
Hans Chulhee Lee ◽  
Sheeba K. Thomas ◽  
Behrang Amini ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Residual Disease ◽  
Response Assessment ◽  
Study Groups ◽  
Prognostic Indicator ◽  
Initial Therapy ◽  
Rank Test ◽  
New Treatments ◽  
The Impact

8024 Background: MRD is a standard measurement for response assessment in MM. Despite new treatments, HRM patients continue to have poor prognosis. We evaluated the impact of MRD- in high vs standard (SRM) risk patients. Methods: We retrospectively evaluated all consecutive MM/plasma cell leukemia patients who had routine MRD testing by 1-tube 8-color advanced flow cytometry with 2,000,000 events and sensitivity level 10-5 at our center from 2015-2018 after initial therapy. Kaplan-Meier and log-rank test were used to assess survival estimates and differences between study groups. Results: 136 patients with MRD testing after initial therapy/autologous transplant (ASCT) were identified. Patient and disease characteristics are included in Table. At a median follow-up of 14 months (1-36), PFS and OS were significantly worse in HRM vs SRM. During the study period, 50% of HRM had progressed (relapse and/or death) vs 20% in SRM (p=0.0006). No patients with SRM died, but 4 (14%) in the HRM group did (p=0.0007). Regardless of MRD status, HRM patients had statistically significant worse PFS than SRM; at median f/u 10% SRM MRD-; 20% SRM MRD+; 40%HRM MRD-; 45% HRM MRD+ had either relapsed or died (p=0.0041). MRD status did not impact OS in either group (p=0.0914), however longer follow up is needed to assess survival. Conclusions: Genetic abnormalities (FISH/GEP) remain a powerful prognostic indicator for myeloma regardless of MRD status. For newly diagnosed myeloma patients treated with novel triple initial therapy and frontline ASCT, achieving MRD negative status didn’t mitigate the poor prognosis outcomes of HRM. [Table: see text]

Revised Response Criteria for Malignant Lymphoma

2007 ◽  
Vol 25 (5) ◽  
pp. 579-586 ◽  
Author(s):  
Bruce D. Cheson ◽  
Beate Pfistner ◽  
Malik E. Juweid ◽  
Randy D. Gascoyne ◽  
Lena Specht ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Study Groups ◽  
Therapeutic Agents ◽  
Emission Tomography ◽  
Response Criteria ◽  
Regulatory Agencies ◽  
Positron Emission ◽  
Group Response ◽  
Biotechnology Companies ◽  
New Guidelines

PurposeStandardized response criteria are needed to interpret and compare clinical trials and for approval of new therapeutic agents by regulatory agencies.MethodsThe International Working Group response criteria (Cheson et al, J Clin Oncol 17:1244, 1999) were widely adopted, but required reassessment because of identified limitations and the increased use of [18F]fluorodeoxyglucose-positron emission tomography (PET), immunohistochemistry (IHC), and flow cytometry. The International Harmonization Project was convened to provide updated recommendations.ResultsNew guidelines are presented incorporating PET, IHC, and flow cytometry for definitions of response in non-Hodgkin's and Hodgkin's lymphoma. Standardized definitions of end points are provided.ConclusionWe hope that these guidelines will be adopted widely by study groups, pharmaceutical and biotechnology companies, and regulatory agencies to facilitate the development of new and more effective therapies to improve the outcome of patients with lymphoma.

scholarly journals Disease monitoring with quantitative serum IgA levels provides a more reliable response assessment in multiple myeloma patients

Leukemia ◽  
2021 ◽  
Author(s):  
Alissa Visram ◽  
Iuliana Vaxman ◽  
Abdullah S. Al Saleh ◽  
Harsh Parmar ◽  
Angela Dispenzieri ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Disease Progression ◽  
Progression Free Survival ◽  
Response Assessment ◽  
Response Criteria ◽  
Disease Assessment ◽  
Disease Response ◽  
Serum Iga ◽  
Trial Endpoints ◽  
Monoclonal Proteins

AbstractUnlike IgG monoclonal proteins (MCPs), IgA MCP quantification is unreliable due to beta-migration of IgA MCPs on serum protein electrophoresis (SPEP). The utility of nephelometric quantitative IgA (qIgA) to monitor IgA multiple myeloma (MM) is unclear. We retrospectively studied disease response kinetics using qIgA versus MCPs by SPEP, and developed and validated novel qIgA disease assessment criteria in 491 IgA MM patients. The SPEP MCP nadir occurred a median of 41 (IQR 0–102) days before the qIgA. The median time to achieve a partial response (PR) was shorter using standard IMWG versus qIgA response criteria (32 vs 58 days, p < 0.001). Stratification by qIgA criteria, unlike IMWG criteria, led to clear separation of the progression-free survival curves of patients achieving a PR or very good PR. There was a consistent trend toward earlier detection of disease progression using qIgA versus IMWG progression criteria. In conclusion, monitoring IgA MM using MCP-based IMWG criteria may be falsely reassuring, given that MCP levels on SPEP decrease faster than qIgA levels. The qIgA response criteria more accurately stratify patients based on the progression risk and may detect disease progression earlier, which may lead to more consistent measurement of trial endpoints and improved patient outcomes.

Recommendations for revised response criteria for malignant lymphoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7507-7507 ◽  
Author(s):  
B. D. Cheson ◽  
B. Pfistner ◽  
M. E. Juweid ◽  
S. J. Horning ◽  
B. Coiffier ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Tumor Size ◽  
Molecular Genetic ◽  
Study Groups ◽  
Response Criteria ◽  
Regulatory Agencies ◽  
Mantle Cell ◽  
Pre Treatment ◽  
Relapsed Disease ◽  
Improve Patient

7507 Background: Standardized response criteria are needed to interpret and compare clinical trials, and for approval of new therapeutic agents by regulatory agencies. Methods: The International Working Group (IWG) criteria (Cheson et al, JCO 17:1244, 1999) were widely adopted but were reevaluated because of limitations identified, and recent advances, notably FDG-PET, immunohistochemistry (IHC) and flow cytometry. Results: We propose the following modifications for non-Hodgkin’s lymphoma (NHL) and Hodgkin lymphoma (HL). For predictably PET avid histologies (PA)(e.g., diffuse large B-cell NHL (DLBCL), HL, follicular (FL) and mantle cell lymphoma (MCL), PET pretreatment is strongly encouraged to define sites of disease, but not required. For histologies not predictably PET+ (NPA), PET should only be done if response is an endpoint. Although PET performed after ≥1 cycles of chemotherapy correlates with treatment efficacy, in the absence of data that altering therapy because of PET results improves outcome, mid-treatment PET should only be done in a clinical trial. PET is essential to assess response in DLBCL and HL, but only in FL and MCL if response is the endpoint. For NPA histologic subtypes, PET should only be used if PET+ prior to therapy and response is a major endpoint. Present data are inadequate to recommend PET for routine post-treatment surveillance. The new definition for CR includes: 1) no signs or symptoms of disease; 2) PET- in a PA lymphoma, or negative CT in NPA lymphoma. 3) Normal bone marrow by morphology, or if indeterminate, negative by IHC, flow and/or molecular genetic studies. CR unconfirmed (CRu) is no longer included. PR is defined as 1) ≥ 50% decrease in tumor size, but PET+ at prior PA sites, or 2) ≥ 50% decrease in tumor size, but CT+ and PET- if PET- prior to treatment. Bone marrow is irrelevant if positive pre-treatment. Stable disease is neither PR nor progressive disease, PET+ only at prior sites of disease. Progressive/ relapsed disease requires ≥ 50% increase in disease or new lesions that are PET+ if PA lymphoma. PET does not replace a biopsy before initiating new therapy. Conclusions: We hope these revised recommendations will be adopted by study groups and regulatory agencies to facilitate the development of new and more effective therapies to improve patient outcome. No significant financial relationships to disclose.

scholarly journals Clinical End Points and Response Criteria in Mycosis Fungoides and Sézary Syndrome: A Consensus Statement of the International Society for Cutaneous Lymphomas, the United States Cutaneous Lymphoma Consortium, and the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer

2011 ◽  
Vol 29 (18) ◽  
pp. 2598-2607 ◽  
Author(s):  
Elise A. Olsen ◽  
Sean Whittaker ◽  
Youn H. Kim ◽  
Madeleine Duvic ◽  
H. Miles Prince ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Mycosis Fungoides ◽  
The United States ◽  
Cutaneous Lymphoma ◽  
Response Criteria ◽  
Sézary Syndrome ◽  
Sezary Syndrome ◽  
End Points ◽  
Cutaneous Lymphomas ◽  
Hodgkin's Lymphomas

Mycosis fungoides (MF) and Sézary syndrome (SS), the major forms of cutaneous T-cell lymphoma, have unique characteristics that distinguish them from other types of non-Hodgkin's lymphomas. Clinical trials in MF/SS have suffered from a lack of standardization in evaluation, staging, assessment, end points, and response criteria. Recently defined criteria for the diagnosis of early MF, guidelines for initial evaluation, and revised staging and classification criteria for MF and SS now offer the potential for uniform staging of patients enrolled in clinical trials for MF/SS. This article presents consensus recommendations for the general conduct of clinical trials of patients with MF/SS as well as methods for standardized assessment of potential disease manifestations in skin, lymph nodes, blood, and visceral organs, and definition of end points and response criteria. These guidelines should facilitate collaboration among investigators and collation of data from sponsor-generated or investigator-initiated clinical trials involving patients with MF or SS.

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