Imaging for diagnosis, staging and response assessment of Hodgkin lymphoma and non-Hodgkin lymphoma

2019 ◽  
Vol 49 (11) ◽  
pp. 1545-1564 ◽  
Author(s):  
Kathleen M. McCarten ◽  
Helen R. Nadel ◽  
Barry L. Shulkin ◽  
Steve Y. Cho
Keyword(s):  
Hodgkin Lymphoma ◽  
Response Assessment ◽  
Non Hodgkin Lymphoma

scholarly journals Ixazomib in Previously Untreated Indolent B-Cell Non-Hodgkin Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5326-5326
Author(s):  
Solomon A. Graf ◽  
Ryan C. Lynch ◽  
David G. Coffey ◽  
Mazyar Shadman ◽  
Sandra Kanan ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Research Funding ◽  
Response Assessment ◽  
Clinical Indication ◽  
Non Hodgkin Lymphoma ◽  
Tumor Reduction ◽  
Frontline Treatment ◽  
Grade 3 ◽  
Indication For Treatment

Abstract Background: Frontline treatment of indolent B-cell non-Hodgkin lymphoma (iB-NHL) typically involves intravenously administered anti-CD20 monoclonal antibodies with or without cytotoxic chemotherapy. Effective and low-toxicity therapies with improved convenience of administration are sought. We hypothesized that ixazomib (Ix) could safely and conveniently induce remissions in patients with untreated iB-NHL. Here we present the first data on frontline use of Ix in untreated iB-NHL. Methods: This single-arm, open-label phase II "window" trial for patients with untreated iB-NHL (NCT02339922) opened to enrollment in May 2016. Eligibility included histopathologically confirmed iB-NHL, measurable disease, a clinical indication for treatment based on NCCN guidelines, and no prior systemic treatment. Ix was administered at 4 mg orally once a week on consecutive 28-day cycles until disease progression or unacceptable toxicity and four doses of weekly rituximab (R) were added during the 7th cycle, after the initial window period. The primary endpoint was investigator-assessed response rate after independent radiology review. Response assessment occurred at every 2 cycles and using standard (Lugano) criteria. Tumor tissue was collected for gene expression profiling and immunohistochemical evaluation of molecular pathways associated with proteasome inhibition. Results: As of July 1, 2018, 15 patients were treated. The median age was 64 years (range, 47 to 81) and 53% were men. Disease histologies included follicular lymphoma (FL, n = 10), mantle cell lymphoma (MCL, n = 2), marginal zone lymphoma (MZL, n = 2), and small lymphocytic lymphoma (SLL, n = 1). At the start of therapy, all had stage III/IV disease and B-symptoms were present in 40%. For patients with FL, 80% had poor risk by FLIPI. Overall, the indication for treatment included symptoms due to disease (40%), steady progression of disease (33%), and cytopenia due to disease (27%). To date, 14 patients were evaluable for response and 13 experienced tumor burden reduction during the Ix-only window (Figure 1). Of patients with FL, 6 completed the Ix-only window phase and, of these, 5 achieved PR. An additional 4 patients with FL have not completed all 6 cycles of Ix monotherapy. Of these, 1 patient achieved a PR after 4 cycles and continues on treatment, 1 patient came off study with stable disease after 4 cycles, and 2 patients have experienced tumor reduction without meeting formal response criteria and continue on treatment (after 2 and 4 cycles, respectively). Of those patients with FL that received R, all achieved formal remission (3 CR, 3 PR). Median progression free survival has not been reached with a median follow up of 7.4 months. No patient with non-FL histology had yet achieved a PR during the Ix-only window or had undergone response assessment after receiving R at the time of the data cut. The most common adverse events (AEs) for all pts were grade 1-2 and included nausea (53%), diarrhea (53%), rash (40%), and fatigue (33%). Peripheral neuropathy occurred in 20% patients (grade 2 in 7%). A single grade ≥ 3 AE occurred (syncope, grade 3). Conclusions: Data from this interim analysis suggest that Ix monotherapy is well tolerated and highly active in the frontline treatment of FL with all patients demonstrating tumor reduction to date and augmented responses following the addition of R. Non-FL histologies of B-NHL appear less responsive to Ix, but numbers are small. Accrual on study continues. Correlative analyses are underway to determine if Ix or Ix-R may represent a viable frontline option for some patients with iB-NHL. Figure 1. Waterfall plot of response. Number of cycles of treatment received to date indicated for each subject. Four weekly doses of rituximab are added, per protocol, with the 7th cycle of ixazomib. Asterisk indicates treatment on study ongoing. Disclosures Graf: Acerta: Research Funding; TG Therapeutics: Research Funding; Beigene: Research Funding. Lynch:T.G. Therapeutics: Research Funding; Takeda Pharmaceuticals: Research Funding; Rhizen Pharmaceuticals S.A.: Research Funding; Incyte Corporation: Research Funding; Johnson Graffe Keay Moniz & Wick LLP: Consultancy. Shadman:Genentech: Consultancy; Genentech: Research Funding; Verastem: Consultancy; AbbVie: Consultancy; Gilead Sciences: Research Funding; Beigene: Research Funding; Qilu Puget Sound Biotherapeutics: Consultancy; AstraZeneca: Consultancy; TG Therapeutics: Research Funding; Mustang Biopharma: Research Funding; Pharmacyclics: Research Funding; Acerta Pharma: Research Funding; Celgene: Research Funding. Gopal:Pfizer: Research Funding; Aptevo: Consultancy; BMS: Research Funding; Brim: Consultancy; Asana: Consultancy; Seattle Genetics: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Takeda: Research Funding; Merck: Research Funding; Janssen: Consultancy, Research Funding; Spectrum: Research Funding; Incyte: Consultancy; Teva: Research Funding.

Response Assessment Using Early and End-of-Treatment 18F-FLT PET Can Predict Outcome in Patients with Non-Hodgkin Lymphoma,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3679-3679
Author(s):  
Hyewon Lee ◽  
Seok-Ki Kim ◽  
Tae Sung Kim ◽  
Se Hun Kang ◽  
Weon Seo Park ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Hodgkin Lymphoma ◽  
Predictive Factor ◽  
Response Assessment ◽  
Early Response ◽  
Independent Predictive Factor ◽  
Predictive Values ◽  
Non Hodgkin Lymphoma ◽  
Flt Pet ◽  
End Of Treatment

Abstract Abstract 3679 Background Fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) scan has been known as a useful modality for response assessment in malignant lymphoma. However, FDG is not tumor-specific and can be false positive in inflammatory lesions. To overcome these limitations, a new PET tracer, thymidine analog 3'-deoxy-3'-18F-fluorothymidine (FLT), was introduced recently. Preliminary data showed close correlation between FLT uptake and tumor cell proliferation in lymphoma, suggesting the possibility of noninvasive tumor grading and early response assessment. Therefore, we performed a prospective trial to evaluate the feasibility of FLT-PET in risk stratification and prediction for treatment outcome, especially in early interim analysis, in patients with non-Hodgkin lymphoma (NHL). Methods Seventy-five patients newly diagnosed with NHL were prospectively enrolled at National Cancer Center, Korea, from Oct 2005 to Oct 2008. All received standard chemotherapy for their pathologic classifications. Patients were evaluated with FLT-PET at baseline (FLT0), after 1 cycle of chemotherapy (FLT1, early), and after completion of the 1st line chemotherapy (FLTE, end-of-treatment). FLT-PET results were assessed according to the International Workshop Criteria (IWC). Maximum standardized uptake values (SUVmax) of each FLT-PET were calculated to evaluate its correlation with the clinical characteristics and treatment outcome. Treatment outcome was estimated using 3-year progression-free survival (3yr-PFS) and overall survival (3yr-OS). Results Of the 75 enrolled patients, 63 (84%) had diffuse large B-cell lymphoma. Median age at diagnosis was 57 years (range, 29–87). Twenty-eight (37.3%) presented with stage III or IV diseases and 20 (26.7%) showed more than 3 IPI scores. Median follow up duration was 4.5 years (range, 3.5–5.8). Five (6.7%) patients underwent hematopoietic stem cell transplantation at last. Three-year PFS and OS rates for all enrolled patients were 68% and 78.7%. Seventy-three (97.3%) had their FLT-PET at baseline, 69 (92%) after 1 cycle of chemotherapy, and 66 (88%) at the end of the 1st line treatment. By IWC, 50 (66.7%) patients achieved complete remission (CR) on FLT1 and 56 (74.7%) had CR on FLTE. Positive predictive values (PPV) of residual uptake on FLT1 and FLTE for relapse or disease progression were 83.3% (95%CI 57.7–95.6) and 80% (95%CI 44.2–96.5), respectively. Negative predictive values (NPV) of them were 88% (95%CI 75.0–95.0) and 82.1% (95%CI 69.2–90.7). Sensitivity and specificity were 71.4% (47.7–87.8) and 93.6% (81.4–98.3) for FLT1 and 44.4% (22.4–67.8) and 95.8% (84.6–99.3) for FLTE, respectively. Complete disappearance of uptake on FLT1 was significantly associated with better PFS compared to residual uptake on FLT1 (3yr-PFS rates, 87.5% and 12.2%, p<0.001). Three-year OS rates according to CR achievement on FLT1 were 96.0% and 27.8%, significantly lower in patients with residual disease after 1 cycle of chemotherapy (p<0.001). SUVmax of FLT0 correlated with LDH level significantly (p=0.044), but not with age (p=0.214), Ki-67 index (p=0.073), IPI score (p=0.270), and Ann Arbor stage (p=0.089). SUVmax of FLT0 were not associated with survival outcomes, however, residual SUVmax of FLT1 reflecting early response to treatment was significantly associated with poor survival outcome (PFS, HR 1.29, 95%CI 1.14–1.47; OS, HR 1.27, 95%CI 1.08–1.49). In multivariate analysis, SUVmax of FLT1 remained as an independent predictive factor for PFS (HR 1.63, 95%CI 1.25–2.13) and for OS (HR 1.89, 95%CI 1.38–2.58). Residual SUVmax of FLTE also revealed to be significantly associated with PFS (HR 1.43, 95%CI 1.05–1.94) and OS (HR 1.59, 95%CI 1.12–2.26) in the same multivariate model. Conclusion Response assessment in cooperation with FLT-PET provided accurate prediction for clinical outcome including PFS and OS in patients with NHL. Especially, early FLT-PET result after 1 cycle of chemotherapy was an independent predictive factor for survival as well as relapse or disease progression, with comparable performance with end-of-treatment FLT-PET. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification

2014 ◽  
Vol 32 (27) ◽  
pp. 3059-3067 ◽  
Author(s):  
Bruce D. Cheson ◽  
Richard I. Fisher ◽  
Sally F. Barrington ◽  
Franco Cavalli ◽  
Lawrence H. Schwartz ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Malignant Lymphoma ◽  
Hodgkin Lymphoma ◽  
Response Assessment ◽  
Disease Extent ◽  
Single Node ◽  
Bulky Disease ◽  
International Conference ◽  
Non Hodgkin Lymphoma ◽  
Positron Emission

The purpose of this work was to modernize recommendations for evaluation, staging, and response assessment of patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). A workshop was held at the 11th International Conference on Malignant Lymphoma in Lugano, Switzerland, in June 2011, that included leading hematologists, oncologists, radiation oncologists, pathologists, radiologists, and nuclear medicine physicians, representing major international lymphoma clinical trials groups and cancer centers. Clinical and imaging subcommittees presented their conclusions at a subsequent workshop at the 12th International Conference on Malignant Lymphoma, leading to revised criteria for staging and of the International Working Group Guidelines of 2007 for response. As a result, fluorodeoxyglucose (FDG) positron emission tomography (PET)–computed tomography (CT) was formally incorporated into standard staging for FDG-avid lymphomas. A modification of the Ann Arbor descriptive terminology will be used for anatomic distribution of disease extent, but the suffixes A or B for symptoms will only be included for HL. A bone marrow biopsy is no longer indicated for the routine staging of HL and most diffuse large B-cell lymphomas. However, regardless of stage, general practice is to treat patients based on limited (stages I and II, nonbulky) or advanced (stage III or IV) disease, with stage II bulky disease considered as limited or advanced disease based on histology and a number of prognostic factors. PET-CT will be used to assess response in FDG-avid histologies using the 5-point scale. The product of the perpendicular diameters of a single node can be used to identify progressive disease. Routine surveillance scans are discouraged. These recommendations should improve evaluation of patients with lymphoma and enhance the ability to compare outcomes of clinical trials.

The value of positron emission tomography in prognosis and response assessment in non-Hodgkin lymphoma

2010 ◽  
Vol 51 (sup1) ◽  
pp. 28-33 ◽  
Author(s):  
Kieron Dunleavy ◽  
George Mikhaeel ◽  
Laurie H. Sehn ◽  
Rodney J. Hicks ◽  
Wyndham H. Wilson
Keyword(s):  
Positron Emission Tomography ◽  
Hodgkin Lymphoma ◽  
Response Assessment ◽  
Emission Tomography ◽  
Non Hodgkin Lymphoma ◽  
Positron Emission

PET-guided treatment for personalised therapy of Hodgkin lymphoma and aggressive non-Hodgkin lymphoma

2021 ◽  
pp. 20210576
Author(s):  
Elizabeth H Phillips ◽  
Rohan Iype ◽  
Andrew Wirth
Keyword(s):  
Hodgkin Lymphoma ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Response Assessment ◽  
Prognostic Information ◽  
Non Hodgkin Lymphoma ◽  
Large B Cell Lymphoma ◽  
Pet Scanning ◽  
Personalised Therapy

FDG-PET scanning has a central role in lymphoma staging and response assessment. There is a growing body of evidence that PET response assessment during and after initial systemic therapy can provide useful prognostic information, and PET response has an evolving role in guiding patient care. This review provides a perspective on the role of PET response assessment for individualised management of patients with the most common aggressive lymphomas, Hodgkin lymphoma and diffuse large B-cell lymphoma.

scholarly journals Current and Future Role of Medical Imaging in Guiding the Management of Patients With Relapsed and Refractory Non-Hodgkin Lymphoma Treated With CAR T-Cell Therapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Laetitia Vercellino ◽  
Dorine de Jong ◽  
Roberta di Blasi ◽  
Salim Kanoun ◽  
Ran Reshef ◽  
...  
Keyword(s):  
T Cells ◽  
Hodgkin Lymphoma ◽  
Response Assessment ◽  
T Cell Therapy ◽  
Car T Cells ◽  
Non Hodgkin Lymphoma ◽  
Car T Cell Therapy ◽  
Pet Ct ◽  
Car T ◽  
Fdg Pet Ct

Chimeric antigen receptor (CAR) T-cells are a novel immunotherapy available for patients with refractory/relapsed non-Hodgkin lymphoma. In this indication, clinical trials have demonstrated that CAR T-cells achieve high rates of response, complete response, and long-term response (up to 80%, 60%, and 40%, respectively). Nonetheless, the majority of patients ultimately relapsed. This review provides an overview about the current and future role of medical imaging in guiding the management of non-Hodgkin lymphoma patients treated with CAR T-cells. It discusses the value of predictive and prognostic biomarkers to better stratify the risk of relapse, and provide a patient-tailored therapeutic strategy. At baseline, high tumor volume (assessed on CT-scan or on [18F]-FDG PET/CT) is a prognostic factor associated with treatment failure. Response assessment has not been studied extensively yet. Available data suggests that current response assessment developed on CT-scan or on [18F]-FDG PET/CT for cytotoxic systemic therapies remains relevant to estimate lymphoma response to CAR T-cell therapy. Nonetheless, atypical patterns of response and progression have been observed and should be further analyzed. The potential advantages as well as limitations of artificial intelligence and radiomics as tools providing high throughput quantitative imaging features is described.

scholarly journals Nivolumab Induces Remission in High- PD-L1 Expressing Aggressive B-Non Hodgkin Lymphoma: A Single Center Experience

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1865-1865 ◽  
Author(s):  
Stephan R Bohl ◽  
Stefan Schoensteiner ◽  
Henriette Huber ◽  
Florian Kuchenbauer ◽  
Peter Moeller ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
B Cell Lymphoma ◽  
Response Assessment ◽  
Grey Zone ◽  
Phase Ii Trials ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Non Hodgkin Lymphoma ◽  
Number Of Patients

Abstract Patients with relapsed or refractory aggressive B-cell Non-Hodgkin lymphoma (B-NHL) have a poor outcome. Nivolumab (NV) targeting the PD-1 receptor has shown promising results in several malignancies like melanoma, renal and lung carcinoma and Hodgkin lymphoma. Data for aggressive B-NHL are just emerging. PD-L1 expression does not necessarily correlate with response. Among lymphoma subtypes, the expression of PD-L1 seems to vary. So far there are no valid data on PD-L1 expression in aggressive lymphoma under NV treatment. We retrospectively analyzed seven patients who had aggressive B-NHL with a refractory or relapsed disease after at least 3 regimens and were thereupon treated with NV 3mg/kg once a fortnight. Treatment was initiated after signed informed consent for off-label use. The histologic specimens were analyzed for PD-L1 expression by immunohistochemistry (IHC). The median age at NV treatment start was 51 years (27-71). The histopathological diagnoses were primary mediastinal B-cell lymphoma (PMBL; n=2), composite lymphoma with diffuse large B-cell (DLBCL) and Hodgkin lymphoma components (n=2), follicular lymphoma transformed into a DLCBL (n=2) and one mediastinal grey zone lymphoma (MGZL). A median of 5 (3-7) prior therapy regimens were given including hematopoietic stem cell transplantation (HSCT) for 3 patients: autologous (n=2) and allogeneic HSCT (n=1), respectively. The lymphoma status was refractory in 2 patients and relapsed in 5 patients. PD-L1 expression was detected in 5 cases, 3 of them showing a positive staining of 10%, 30%, and 50%, respectively, and 2 cases even of 100% of the lymphoma cells. NV was mostly well tolerated (1 pneumonitis completely resolved after systemic steroid therapy, 1 unrelated death caused by septic shock) with a median of 3 (1-17) cycles administered. Response assessment (clinical examination, ultrasound, CT or PET-CT scans) were performed after a median of 3 cycles (2-7), showing regressive and refractory disease in 3 patients, respectively, while 1 patient died prior to response assessment. Among the three responders (2xCR, 1xPR) MGZL and PBML their tumors had high PD-L1 expression of 30% (n=1) and 100% (n=2), respectively. Two responders (one after autologous, one after allogeneic HSCT) are still under treatment. After 14 weeks, one responding patient showed signs of progression of a previously known cerebral lesion (or pseudo progression under immunotherapy). The third responder proceeded to allogeneic HSCT without relevant complications. The PD-L1 expression among the non-responders were 0% (n=2) with progressive disease being the cause of death and 10% (n=1) for the other who is currently receiving alternative therapy. In conclusion, NV induces remission in heavily pretreated, PD-L1 high expression aggressive B-NHL. The significance of these data are limited due to the small number of patients. Therefore, future results of current phase II trials (NCT02038933) will reveal the role of PD-1 blockade in aggressive B-NHL. Disclosures Viardot: Roche: Honoraria; Takeda: Other: travel support; Pfizer: Honoraria; BMS: Consultancy; Janssen: Consultancy; Amgen: Consultancy.

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