Advanced-stage Hodgkin Lymphoma Patients Research Articles

Prognostic value of chest x-ray- and CT-defined large mediastinal adenopathy in high-risk pediatric Hodgkin lymphoma: A report from the Children's Oncology Group Study AHOD0831.

We compared the prognostic value of chest radiograph (CXR)- and computed tomography (CT)-derived definition of large mediastinal adenopathy (LMA) in pediatric Hodgkin lymphoma (HL). Total 143 patients treated for stage IIIB/IVB HL on COG AHOD0831 were included in this study. Six definitions of LMA were investigated: (i) mediastinal mass ratio on CXR (MRCXR )>1/3; (ii) mediastinal mass ratio on CT (MRCT )>1/3; (iii) mediastinal mass volume on CT (MVCT )>200mL; (iv) normalized mediastinal mass volume (MVCT /thoracic diameter [TD])>1mL/mm; (v) mediastinal mass diameter on CT (MDCT )>10cm; and (vi) normalized mediastinal mass diameter (MDCT /TD)>1/3. Median age at diagnosis was 15.8years (range: 5.2-21.3years). In patients with a slow early response (SER) to chemotherapy, MVCT >200mL, MDCT >10cm, and MDCT /TD>1/3 were associated with worse relapse-free survival (RFS) on MVA, while MRCXR >1/3, MRCT >1/3, and MVCT /TD>1mL/mm trended toward worse RFS; MDCT /TD was the most strongly prognostic for inferior RFS, with a hazard ratio of 6.41 for MDCT /TD>1/3 versus ≤1/3 on MVA (p=.02). LMA according to MVCT >200mL, MDCT >10cm, and MDCT /TD>1/3 is associated with poor prognosis in advanced-stage HL patients with SER. The normalized mediastinal diameter, MDCT /TD>1/3 appears to be the strongest predictor of inferior RFS.

Influence of Sociodemographic Determinants on the Hodgkin Lymphoma Baseline Characteristics in Long Survivors Patients Enrolled in the Prospective Phase 3 Trial AHL2011.

Whereas numerous studies on several cancers describe the link between social conditions and disease severity, little is known about the social and demographic characteristics of Hodgkin lymphoma (HL) patients. At diagnosis, 10-15% of the patients in the advanced stages have a well-known poor outcome owing to their chemoresistance, but the determinants of the more advanced stages remain elusive. The objective of the present study was to decipher the potential impact of social disparities on the disease features at diagnosis and analyze how the sociodemographic patient features could impact the HL outcome of patients with advanced-stage HL enrolled in the AHL2011 trial. This ancillary study was conducted on a cohort of patients from French centers that had recruited more than five patients in the phase III AHL2011 study (NCT0135874). Patients had to be alive at the time of the ancillary study and had to have given their consent to answer the questionnaire. Pre-treatment data (age, gender, stage, B symptoms, IPS), the treatment received, the responses to PET-CT, and the presence of serious adverse events (serious adverse events-SAEs) were all extracted from the AHL2011 trial database. Sociodemographic data-marital status, living area, level of education, socio-professional category, and professional situation-were extracted from the questionnaires. The population density at the point of diagnosis was determined based on ZIP Code, and the distance from the reference medical center was then calculated by the road network. Baseline PET acquisition was performed before any treatment. PET images at baseline were centrally reviewed. The total metabolic tumor volume (TMTV) at the baseline was calculated using a 41% SUVmax cutoff for each lesion. Progression-free survival was defined as the time from randomization to the first progression, relapse, or death from any cause or the last follow-up. The data cutoff for the analyses presented here was 31 October 2017. The progression-free survival was analyzed on an intention-to-treat basis. Among the 823 patients enrolled in the AHL2011 study, the questionnaire was sent to 394 patients, of whom 232 (58.9%) responded. At the time of HL diagnosis, 61.9% (N = 143) of patients declared that they were not socially isolated, 38.1% (N = 88) that they were single, 163 (71.2%) had a professional activity, and 66 (28.8%) were inactive owing to unemployment, retirement, or sick leave. Of the patients, 31.1% (N = 71) lived in a rural region, compared to 68.9% (N = 157) that lived in an urban region. The residence ZIP Code at the time of HL diagnosis was available for 163 (70%). Sociodemographic characteristics did not influence the presence of usual prognostic factors (ECOG, B symptoms, bulky mass, IPS) except for professional activity, which was associated with more frequent low IPS (0-2) (79 (48.5%) active versus 20 (30.3%) inactive patients; p = 0.012). Likewise, no correlation was observed between TMTV and sociodemographic characteristics. However, the TMTV quartile distribution was different according to the living area, with the two upper quartiles being enriched with patients living in a rural area (p = 0.008). Moreover, a negative correlation between the average number of the living area's inhabitants and TMTV (R Pearson = -0.29, p = 0.0004) was observed. This study focused on sociodemographic parameters in advanced-stage HL patients and shows that professional activity is associated with more favorable disease features (low IPS), while patients living in rural or low-populated areas are more likely to have an unfavorable HL presentation with a high tumor burden (high TMTV). These data suggest that some patient sociodemographic characteristics might impact either access to medical care or environmental exposure, leading to a higher frequency of unfavorable presentations. Further prospective sociodemographic studies are necessary to confirm these preliminary results.

T001: FDG-PET and serum TARC levels after one cycle of BV-AVD in advanced stage Hodgkin lymphoma patients: results from the very early PET-response adapted EORTC-COBRA trial

T001: FDG-PET and serum TARC levels after one cycle of BV-AVD in advanced stage Hodgkin lymphoma patients: results from the very early PET-response adapted EORTC-COBRA trial

P008: Impact of bone marrow involvement on early PET response and progression-free survival in the HD18 trial for patients with advanced-stage Hodgkin lymphoma

Background: The prognostic role of bone marrow (BM) involvement in advanced-stage Hodgkin lymphoma is unclear, particularly for patients receiving intensive first-line treatment. We thus retrospectively examined its impact on early response and progression-free survival (PFS) among individuals receiving escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) in the HD18 trial. Patients and Methods: A total of 424 individuals were suitable for analysis, of which 124 (29%) had BM involvement according to initial positron emission tomography (PET). Patient outcome was measured by PET response after 2×eBEACOPP and five-year PFS rate. Results: After 2×eBEACOPP, 79 of the BM PET-negative individuals (26%) and 26 of the BM PET-positive patients (21%) were found to be PET-positive (odds ratio [OR] 0.74, P=0.25). The five-year PFS rate was 90.7% in BM PET-negative individuals and 91.8% for BM PET-positive patients (hazard ratio 0.82, P=0.6). In our BM PET-positive subgroup, nine (16%) of the 56 subjects with one or two sites of skeletal uptake were PET-positive after 2×eBEACOPP as compared to 17 (25%) of the 68 individuals showing three or more BM lesions (OR 1.74, P=0.23). Conclusions: The present analysis demonstrates that BM involvement, irrespective of its extent, does not lead to increased risk for a positive interim PET result or inferior PFS in advanced-stage Hodgkin lymphoma patients undergoing eBEACOPP treatment. Skeletal lesions cannot therefore be considered as an additional prognostic marker of therapy failure or disease recurrence for individuals receiving intensive first-line treatment.

Lesion Dissemination in Baseline PET/CT (D-MAX) and IPS Score Predict ABVD Treatment Outcome in PET-2 Negative Advanced-Stage Hodgkin Lymphoma Patients Enrolled in the Prospective GITIL/FIL HD0607 Trial

Background: Despite its high overall accuracy in predicting ABVD outcome in advanced stage Hodgkin Lymphoma (HL), interim PET performed after 2 chemotherapy cycles (PET-2) showed a sub-optimal negative predictive value (PV) on treatment response. In fact, PET-2 negative patients (p.) treated with six ABVD cycles in four prospective trials (RATHL, GITIL/FIL HD 0607, SWOG 0816 and Echelon-1), showed a 3-Y PFS ranging between 79% to 87%, even declining to 74% after a 5-year follow-up (Stephens 2019). A high Total Metabolic Tumor Volume (TMTV) calculated in baseline PET (cutoff value 471 ml.) , along with a high IPS (≥2) proved able to identify a small p. subset (7%) of PET-2 neg. p. with a 3-Y PFS of only 56% (Gallamini 16° ICML, 2021). A new TMTV-derived parameter aimed to image tumor spread, the tumor distance (DMAX), proved able to predict ABVD outcome in a retrospective series of HL p. from a single center (Durmo, 16° ICML 2021). We report here the PV on ABVD outcome of DMAX combined with IPS in a large cohort of PET-2 negative p. prospectively enrolled in the HD0607 clinical trial. Methods: Out of 783 p. with advanced HL (IIB-IVB) included in the HD0607 clinical trial (NCT00795613), 630 (81%) of them with both negative PET-2 and end-of therapy PET, were randomly assigned to no further therapy or consolidation radiotherapy over the area of a large nodal mass detected at baseline. A single experienced nuclear medicine physician calculated DMAX and TMTV in 331 out of 630 (52%) PET-2 negative p. in which the baseline PET images were available for review. Three different tumor segmentation methods for TMTV computing were chosen, with (1) a relative threshold of 41% of SUVmax in each lesion, (2) a fixed threshold of SUV=2.5 or (3) of SUV=4. DMAX was calculated as the maximum distance among any pixel of the tumor belonging to any lesions in the body. Results: The demographics of the 331 p. included in the present study and of the overall cohort of 630 PET-2 negative p. were: median age 31 (14-60) Vs. 31 (14-60), M/F ratio 0.86 Vs. 0.89; WHO Performance Status 0-1 91.5% Vs. 91.4%; B-symptoms 81.8 Vs. 81.1%; Stage IIB, III and IV 35.0, 35.0, 29.9, Vs.36.3, 33.0 and 30.0%; IPS 0-1 39.3 Vs. 39.8%, IPS 2-3 48.3 Vs. 49.4%, IPS >3 12.4 Vs. 10.6%, Bulky 18.1 Vs. 17.9%. No difference in 6-y PFS was found for p. randomized to NFT or cRT (p=.48; Gallamini JCO 2020). After a median follow-up of 40.6 (4.8-87.2) months, the 3-Y PFS for the 331 p. included in the present analysis and for all the 630 PET-2 negative p. was 84% (95% CI 81% to 87%) and 87% (95% CI, 84% to 89%), respectively. Treatment failure was recorded in 51/331 (15.4%) and 81/627 (12.9%), respectively. Based on a ROC analysis the three different segmentation methods for MTV computing proved to be equivalent (AUC values 0.620-0.525) and hence the 41% threshold was chosen for consistency with previous works. Median and average DMAX values were 12.5 cm. and 15.3 cm. The most accurate cutoff value for DMAX to predict treatment outcome (3-Y PFS) was 16.2 cm., with an AUC of 0.62 (95% CI 0.53-0.70). With this cutoff value DMAX was able to identify two cohorts of patients with a statistically different 3y-PFS: 90% (CI 85-93%) and 76% (95% CI 69-85%), p < 0.001. In multivariate analysis (Cox regression model) including all the above demographics and clinical parameters, as well as TMTV and DMX, only DMAX turned out significant in predicting relapse, with a HR of 1.46 (95% CI1.06-2.01), p=0.02. Upon combining DMAX (higher or lower than 16.2 cm.) and IPS (0-1 Vs. ≥2) in a two-factor predictive model, three categories of p. with a statistically different treatment outcome (P < 0.0001) have been identified: (1) both low DMAX and low IPS, N =30 (9%), 3-Y PFS 100% (95% CI 96-100); (2) either high DMAX and low IPS or high IPS and low DMAX, N= 198 (60%); 3-Y PFS 88% (95% CI 83-93), and (3) both high DMAX and IPS, N= 103 (31%); 3-Y PFS 72% (95% CI 65-82), p<0.0001. Conclusions: DMAX and IPS combined in a predictive model were able to single out three classes of PET-2 negative p. with a statistically different ABVD outcome. P. with a high MTV and a high DMAX, accounting for nearly one-third of p. included in the study, showed the highest risk of failing ABVD, with only 72% of them sustaining a long-term disease control at three years, thus deserving a more aggressive or innovative treatment. The remaining two-thirds had a very good outcome, with a 3-y PFS of 90%, thus stressing that ABVD could remain the standard of care for most PET-2 negative p. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Early PET-CT to Guide Escalated Therapy in Advance Stage Hodgkin Lymphoma

BackgroundNowadays treatment for advanced stage Hodgkin lymphoma (LH) remains controversial. ABVD therapy has been historically the standard of care, later on, more sustained dose / intensity regimens like BEACOPP have emerged and improved progression-free survival of patients through better initial control of the disease but without significant overall survival profit due to potentially increased immediate and delayed toxicity. More recently, PET directed strategy with escalation or de-escalation protocols based on the response to the early PET-CT have shown promising results in finding the best way to balance optimal control of the disease with lesser treatment related toxicity.We report here our experiment of treatment escalation in case of positive PET-CT after 2 cycles of ABVD (PET-CT 2) as first-line therapy patients with advanced Hodgkin lymphoma.MethodsBetween 2008 and 2016, 102 patients with Hodgkin lymphoma underwent PET-CT evaluation at diagnosis and after 2 cycles of treatment, 50 had advanced disease (Stage III or IV of Ann Arbor) among witch, 47 received ABVD, 2 BEACOPP and 1 VABEM as initial therapy. The metabolic responses were assessed according to the Deauville criteria.ResultsBefore initiating treatment, the prognosis of the patients was intermediate for 24 patients (48%) and unfavorable for 20 (40%), the median of age was 48 years (min-max: 19-85). Escalated treatment was needed for the 11 patients (22%) refractory to ABVD protocol. The median PFS was 66 months (47-85) and median overall survival (OS) was not achieved; OS at 60 months was 65%. We found no difference in survival between patients with negative PET-CT and those with positive PET-CT, who have benefited from an escalation of treatment.ConclusionThis study evaluated escalating first-line treatment ABVD for advanced stage Hodgkin lymphoma patients with positive PET-CT 2. This management aims to reduce the toxicity of intensive treatments when good control of the disease is asserted. One goal of our study is also to identify the higher risk patients for whom more intensive treatment could be used as first-line treatment. DisclosuresLeleu:Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pierre Fabre: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

Early Reduction of Serum TARC Levels Predicts Prognosis of Patients Treated with a PET-Adapted Strategy for Advanced Stage Hodgkin Lymphoma (HL) in the GITIL/FIL HD0607 Trial

Background: Elevated serum levels of the thymus and activation-regulated chemokine/CCL17 (TARC) reflect tumor burden in classical HL at diagnosis and their reduction during treatment can predict prognosis. Interim PET, performed after 2 cycles of ABVD (PET2), proved to be highly effective in identifying advanced-stage HL patients at risk of failure by continuing ABVD (Gallamini A et al. J Clin Oncol 2007;25:3746), whereas their prognosis could be improved by shifting to BEACOPP escalated (Gallamini A et al. Haematologica 2017;102s: S413). Nevertheless, a not negligible fraction of patients (13%-15%) despite a negative PET2 is reported to experience failure with ABVD, and only 60% of patients are expected to be salvaged by BEACOPP escalated. Therefore, the evaluation of biomarkers like serum TARC levels, an easy to perform and relatively inexpensive procedure, could be useful to assess risk of disease progression in patients treated with a PET-adapted strategy. The aim of this study was to evaluate the correlation of PFS and early serum TARC levels reduction in patients with advanced-stage HL treated according to HD0607 PET-driven trial.MethodsHD0607 trial was a prospective open label phase II study treating, from June 2008 to June 2014, 782 newly diagnosed advanced-stage HL patients with 2 cycles of ABVD, followed by PET2; PET2-negative patients continued with 4 cycles ABVD and PET2-positive patients were randomized to 4 cycles BEACOPP escalated followed by 4 cycles BEACOPP standard with or without Rituximab. Serum TARC levels were measured by commercially available ELISA test kits (R&D System, Minneapolis, USA) on frozen sera of patients at baseline and after 2 ABVD cycles (T2). The value of 800 pg/mL, representing the 99th centile of TARC distribution in a group of 156 independent healthy subjects, was considered as cut-off value discriminating between normal and abnormal TARC values. The Wilcoxon Mann Whitney test was used to analyze the association between median TARC values and PET2 results or treatment outcome. Kaplan-Meyer curves and log-rank test were used to assess differences in PFS according to TARC levels. Cox model was used for multivariate analysis.ResultsThe serum TARC levels were assessed in 243 patients at baseline and after 2 ABVD cycles. Main patient characteristics were as follows: males/females: 122/121, median age: 31 years (range, 16-60), B symptoms: 86%, bulky disease (>5cm): 59%, stage IIB: 43%, stage III: 31%, stage IV: 26%, IPS>3: 14%. Median (IQ range) TARC values at baseline and after 2 ABVD were: 37855 (13990-73312) and 444 (277-723) pg/mL, respectively. A positive PET2 was recorded in 47/243 (19%) patients and 46/243 (19%)patients experienced disease failure. Median (IQ range) T2 values were significantly higher in PET2-positive patients compared to their counterpart (703, IQ 389-2517 vs 424, IQ 250-656; p<.001), and in patients with progression or relapse compared to those in continuous CR (580, IQ 308-1297 vs 429, IQ 277-661; p=.01). With the selected cut-off of 800 pg/mL, the sensitivity and specificity of T2 in predicting PET2 results and treatment outcome were 0.43, 0.82 and 0.41, 0.82, respectively.As shown in Figure 1, after a median follow-up of 3.6 years, the 3-year PFS for patients with T2 ≤ vs >800 pg/mL was significantly different: 85% vs 66% (p<.001), and T2>800 pg/mL was able to identify patients with a worse prognosis also among those with a negative PET2 (3-year PFS: 77% vs 88%; p=.03). In univariate and multivariate analysis T2 > 800 pg/mL, positive PET2 and IPS>3 significantly affected PFS. T2 was a significant independent predictor of outcome in both the whole study population (HR 2.26; 95% CI :1.22-4.20) and in the PET2 negative patients (HR 2.37; 95% CI: 1.06-5.26).ConclusionsEarly reduction of serum TARC levels, after 2 ABVD cycles, are associated with a favorable outcome in patients treated with a PET-driven strategy. Evaluation of T2 may help identifying those patients at risk of treatment failure despite a negative PET2. [Display omitted] DisclosuresViviani:Takeda Italia: Speakers Bureau; Takeda International: Research Funding. Zanotti:Deciphera: Consultancy. Corradini:Sanofi: Honoraria; Roche: Honoraria; Gilead: Honoraria; Takeda: Honoraria; Novartis: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Amgen: Honoraria. Rambaldi:Novartis, Amgen, Celgene, Sanofi: Other: Travel, Accomodations, Expenses; Novartis, Roche/Genentech, Amgen, Italfarmaco: Consultancy.

Clinical Profiles, Treatment Characteristics and Outcomes Among Newly Diagnosed Hodgkin Lymphoma Patients Presenting with Unfavorable and Advanced Disease within a US Community Oncology Setting

INTRODUCTIONThe intent of treating newly diagnosed Hodgkin lymphoma (HL) patients is to achieve a complete remission that can eventually translate into a cure. Treatment decisions for HL are guided by several factors, including sub-type, stage, disease symptomatology, laboratory results, radiologic imaging, age and overall health. Understanding patient profiles and treatment characteristics is important as there is a demographic difference between patients treated in community and academic settings. The intent of this study was to improve understanding of the HL patient population and treatment trends among unfavorable-/advanced-stage HL patients receiving care within the US community oncology setting. METHODS: This was a retrospective, observational cohort study of adult HL patients with Stage IIB-IV disease who initiated first-line chemotherapy within the US Oncology Network between 1/1/09 - 6/30/12. Patients were followed until 6/30/16. Most data were captured from structured fields of the electronic healthcare record, with a targeted chart review performed to provide additional detail on select study variables for a subset of the study population. Descriptive analyses were performed to assess patient and treatment characteristics, while the Kaplan Meier method was used to calculate the duration of therapy (DOT), time to next treatment (TTNT) and time to stem cell transplantation (SCT). RESULTS: In total, 565 patients met eligibility criteria and were included in the analysis. The mean age of the patient population was 44.3 years (standard deviation [SD] 18.2), 55.0% were male and 69.2% were Caucasian. Most patients (90.4%) received the ABVD regimen (doxorubicin, bleomycin, vinblastine and dacarbazine) or a variant of the ABVD regimen in the first-line setting (LOT1). Seventy-four (13.1%) patients were as assumed to have relapsed/refractory disease, as evidenced by advancement to second-line (LOT2) therapy. Among these patients, 44.6% received an etoposide-containing regimen, 17.6% received a brentuximab vedotin-containing regimen and 9.5% GVD (gemcitabine, vinorelbine, doxorubicin). Nearly 30% of LOT2 patients received a regimen classified into an “other” category because it was received by less than 5 patients in the study. Following LOT1, the median TTNT was 67.9 weeks (95% confidence interval [CI] 50.8,104.5). Among the 511 patients who received ABVD/ABVD variant regimens in LOT1, the median TTNT was 67.9 weeks (95%CI 49.0,90.9). Compared to LOT1, the median DOT of LOT2 was shorter (22.1 weeks [95%CI not reached] vs. 7.6 [95%CI 6.3, 10.1] weeks). The median DOTs of ABVD/ABVD variants and AVD in LOT1 were 22.1 (95%CI not reached) and 20.1 (95%CI 7.1, 22.1) weeks, respectively. Only 32 patients advanced to LOT3 and 7 to LOT4. Among patients selected for chart review, 31.2% reported symptoms associated with peripheral neuropathy during LOT1. Data pertaining to radiologic imaging and SCT were only available among patients selected for chart review. These results indicated that positron emission tomography (PET) scans were most frequently performed at diagnosis (74.9% of records reviewed) and/or after LOT1 (55.3% of records reviewed). At diagnosis, all PET scan results were positive (Deauville score 4-5); after LOT1 71.7% were negative (Deauville score 1-3). Treatment changes explicitly attributed to PET scan results were infrequently documented. Among the 29 patients observed to have undergone SCT, the median time to SCT was 41.1 weeks (95%CI 32.7, 56.8). CONCLUSIONS: These findings provide insight into the patient profiles and treatment progression in a US community oncology setting. In particular, ABVD/ABVD variant regimens were observed to be the predominate therapy in the front-line setting. Intensive salvage therapy and consolidative SCT were uncommon in the second-line setting, with most patients receiving etoposide- and brentuximab vedotin-containing regimens. Utilization of PET imaging at diagnosis, for interim response assessment and at completion of therapy was not universal. The apparent difference in use of imaging observed in this community oncology setting compared to what is reported by academic centers may be due variation treatment practices across these organizations or underlying differences in their patient populations. Future research should explore how patient profiles influence use of imaging and associated treatment decisions. DisclosuresYasenchak:Seattle Genetics: Consultancy; Bristol-Myers Squibb: Consultancy. Feliciano:Seattle Genetics: Employment, Equity Ownership. Aguilar:McKesson Specialty Health: Employment. Clark:McKesson Specialty Health: Employment, Equity Ownership. Amirian:McKesson Specialty Health: Employment. Richhariya:Seattle Genetics: Employment, Equity Ownership.

The neutrophil to lymphocyte ratio (NLR) and the presence of large nodal mass are independent predictors of early response: A subanalysis of the prospective phase II PET‐2‐adapted HD0607 trial

BackgroundThe neutrophil to lymphocyte ratio (NLR) and the lymphocyte to monocyte ratio (LMR) can reflect both the myeloid dysfunction and T‐cell immune suppression and have prognostic significance.MethodsIn 771 newly diagnosed advanced‐stage Hodgkin Lymphoma (HL) patients we evaluated the baseline values of NLR and LMR as predictors of clinical outcome. According to the multicenter prospective phase II GITIL‐HD0607 trial, all patients received two ABVD courses and if PET‐2 negative received four additional ABVD cycles while if PET‐2‐positive patients were randomized to either BEACOPP escalated (Be) plus BEACOPP baseline (Bb) (4 + 4 courses) or Be + Bb (4 + 4) and Rituximab. PET scans were centrally reviewed by an expert panel by Blinded Independent Central Review.ResultsHigher NLR and lower LMR were associated with a PET‐2 positivity and failure to achieve long‐term disease control, respectively. By univariate and multivariate analysis, large nodal mass (>7 cm), IPS ≥ 3, NLR > 6 were strong independent predictors of early PET‐2 response after ABVD. Only NLR > 6 and IPS ≥ 3 were strong independent predictors of outcome at diagnosis; however, when PET‐2 status was added, only PET‐2‐positive status and IPS ≥ 3 were independent predictors of PFS. Focusing on PET‐2‐negative patients, those with NLR > 6 had an inferior 3‐year PFS compared to patients with NLR ≤ 6 (84% vs 89% months, P = .03).ConclusionIn advanced‐stage HL patients treated with a PET‐2‐driven strategy, IPS ≥ 3 and NLR > 6 are independent predictors of outcome at diagnosis while the presence of large nodal mass, IPS ≥ 3, and NLR > 6 at diagnosis are independent predictors of early ABVD response.

Consolidation Radiotherapy Could Be Safely Omitted in Advanced Hodgkin Lymphoma With Large Nodal Mass in Complete Metabolic Response After ABVD: Final Analysis of the Randomized GITIL/FIL HD0607 Trial.

To investigate the role of consolidation radiotherapy (cRT) in advanced-stage Hodgkin lymphoma (HL) presenting at baseline with a large nodal mass (LNM) in complete metabolic response after doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy. Advanced-stage (IIB-IVB) HL patients, enrolled in the HD 0607 trial (Clinicaltrial.gov identifier NCT00795613), with both a negative PET after two (PET-2) and six (PET-6) ABVD cycles, who presented at baseline with an LNM, defined as a nodal mass with the largest diameter ≥ 5 cm, were prospectively randomly assigned to receive cRT over the LNM or no further treatment (NFT). Among 296 randomly assigned patients, the largest diameter of LNM at baseline was 5-7 cm in 101 (34%; subgroup A) and 8-10 cm in 96 (32%; subgroup B), whereas classic bulky (diameter > 10 cm) was detected in 99 (33%; subgroup C). Two hundred eighty patients (88%) showed a postchemotherapy RM. The median dose of cRT was 30.6 Gy (range, 24-36 Gy). After a median follow-up of 5.9 years (range, 0.5-10 years), the 6-year progression-free survival rate of patients who underwent cRT or NFT was, respectively, 91% (95% CI, 84% to 99%) and 95% (95% CI, 89% to 100%; P = .62) in subgroup A; 98% (95% CI, 93% to 100%) and 90% (95% CI, 80% to 100%; P = .24) in subgroup B; 89% (95% CI, 81% to 98%) and 86% (95% CI, 77% to 96%; P = .53) in subgroup C (classic bulky). cRT could be safely omitted in patients with HL presenting with an LNM and a negative PET-2 and PET-6 scan, irrespective from the LNM size detected at baseline.

4074 The Role of Immortal Time Bias When Linking Treatment to Outcomes among Older Patients with Incident Hodgkin Lymphoma (HL) using Surveillance, Epidemiology and End Results (SEER)-Medicare Data

OBJECTIVES/GOALS: Older patients with HL have worse outcomes than younger patients, which may reflect treatment selection, including fewer chemotherapy cycles. Immortal time bias exists when patients must survival to initiation, and even completion, of treatment. We described treatment length and death to evaluate the extent of immortal time bias. METHODS/STUDY POPULATION: This retrospective cohort study utilized SEER-Medicare data from 1999-2014. Patients diagnosed with incident advanced stage HL at age ≥65 years and enrolled in Medicare Part A and B fee for service were included. Chemotherapy or radiotherapy treatment initiated within 4 months of diagnosis was determined from inpatient, outpatient, and physician/supplier claims. No treatment was defined by lack of treatment claims. Dates from claims were used to define length of treatment; ≥4 months of treatment indicated complete chemotherapy cycles. Date of death was obtained from Medicare data. Analyses were limited to 1 year post-diagnosis. Summary statistics were used to describe treatment length and subsequent death. RESULTS/ANTICIPATED RESULTS: We included 1492 advanced stage HL patients with a mean age of 76 years (SD = 7). 428 (29%) patients had no documented treatment; 397 (27%) were treated &lt;4 months indicating fewer chemotherapy cycles; and 667 (45%) were treated for ≥4 months indicating complete chemotherapy cycles. Among those with no documented treatment, 15% died within 1 month of diagnosis with 78% dying by 1 year post-diagnosis. Among those treated &lt;4 months, 36% died within 1 month of their last treatment claim with 64% dying by 1 year post-diagnosis. Among those treated ≥4 months, 7% died within 1 month of their last treatment claim with 14% dying by 1 year post-diagnosis. DISCUSSION/SIGNIFICANCE OF IMPACT: Few untreated patients died within 1 month of diagnosis. One-third of patients treated &lt;4 months died soon after completion of treatment, while patients treated longer survived longer, suggesting some patients did not survive to complete treatment. To account for this immortal time bias, landmark analysis will be used to assess the relationship between treatment and survival.

Potential impact of consolidation radiation therapy for advanced Hodgkin lymphoma: a secondary analysis of SWOG S0816

The role of radiotherapy (RT) in the management of advanced Hodgkin Lymphoma (HL) is inadequately defined in this era of functional imaging with PET scan. SWOG-S0816 treated advanced stage Hodgkin lymphoma patients with ABVD+/- escBEACOPP and no RT. We queried whether RT might have benefited patients in S0816 who would have met the GHSG-HD15 criteria for RT by simulating RT use as per HD15 criteria of PET + residual disease ≥2.5 cm. Receiver-operating-characteristics analyses were performed by varying disease-control rates within radiation fields and size cutoffs for residual disease. Among the 49 PET3+ S0816 patients, RT would have raised the 2-year PFS from 30.6% to 50.2–58.1% using three residual disease cutoffs (1.5, 2.0 and 2.5 cm) and assuming 80 and 90% in-field control rates . Although there may be improvement in PFS as size cutoff point is lowered, consequential toxicities from RT require further definition to assess relative benefits.

FDG-PET Imaging for Hodgkin and Diffuse Large B-Cell Lymphoma-An Updated Overview.

Since the mid-1990s, 18F-fluorodeoxglucose (FDG)-positron emission tomography (PET) in combination with computed tomography has come to play a prominent role in the management of malignant lymphomas. One of the first PET applications in oncology was the detection of lymphoma manifestations at staging, where it has shown high sensitivity. Nowadays, this imaging modality is also used during treatment to evaluate the individual chemosensitivity and adapt further therapy accordingly. If the end-of-treatment PET is negative, irradiation in advanced-stage Hodgkin lymphoma patients can be safely omitted after highly effective chemotherapy. Thus far, lymphoma response assessment has mainly been performed using visual criteria, such as the Deauville five-point scale, which became the international standard in 2014. However, novel measures such as metabolic tumor volume or total lesion glycolysis have recently been recognized by several working groups and may further increase the diagnostic and prognostic value of FDG-PET in the future.

The classic prognostic factors in advanced Hodgkin\u2019s lymphoma patients are losing their meaning at the time of Pet-guided treatments

The International Prognostic Score (IPS) is the most commonly used risk stratification tool for patients with advanced Hodgkin lymphoma (HL). It incorporates seven clinical parameters independently associated with a poorer outcome: male sex, age, stage IV, hemoglobin level, white blood cell and lymphocyte counts, and albumin level. Since the development of the IPS, there have been significant advances in therapy and supportive care. Recent studies suggest that the IPS is less discriminating due to improved outcomes with ABVD therapy. The aim of the present study was to asses if classic prognostic factors maintain their prognostic meaning at the time of response-adapted treatment based on interim PET scans. We evaluated the prognostic significance of IPS in the 520 advanced stage HL patients enrolled in the PET-guided, HD0801 trial in which PET2-positive patients underwent a more intense treatment with an early stem-cell transplantation after 2 cycles of ABVD. We observed that in these patients, the IPS completely loses its prognostic value together with all the single parameters that contribute to the IPS. Furthermore, neutrophils, monocytes, lymphocytes, and the ratio among them also no longer had any predictive value. We believe that the substantial improvement in survival outcomes in PET2-positive patients treated with early autologous transplantation could explain the complete disappearance of the residual prognostic significance of the IPS.

Five-year follow-up of SWOG S0816: limitations and values of a PET-adapted approach with stage III/IV Hodgkin lymphoma

AbstractPatients with advanced-stage Hodgkin lymphoma (HL) demonstrated excellent 2-year progression-free survival (PFS) after receiving positron emission tomography (PET)–adapted therapy on SWOG S0816. Patients received 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Patients achieving complete response (CR) on PET scan following cycle 2 of ABVD (PET2) continued 4 additional cycles of ABVD. Patients not achieving CR on PET2 were switched to escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) for 6 cycles. After a median follow-up of 5.9 years, a subset of 331 eligible patients with central review of PET2 was analyzed. PET2 was negative in 82% and positive in 18%. For all patients, the estimated 5-year PFS and OS was 74% (95% confidence interval [CI], 69%-79%) and 94% (95% CI, 91%-96%), respectively. For PET2− and PET2+ patients, the 5-year PFS was 76% (95% CI, 70%-81%) and 66% (95% CI, 52%-76%), respectively. Seven (14%) and 6 (2%) patients reported second cancers after treatment with eBEACOPP and ABVD, respectively (P = .001). Long-term OS of HL patients treated on S0816 remains high. Nearly 25% of PET2− patients experienced relapse events, demonstrating limitations ABVD therapy and of the negative predictive value of PET2. In PET2+ patients who received eBEACOPP, PFS was favorable, but was associated with a high rate of second malignancies compared with historical controls. Our results emphasize the importance of long-term follow-up, and the need for more efficacious and less toxic therapeutic approaches for advanced-stage HL patients. This trial was registered at www.clinicaltrials.gov as #NCT00822120.

Early chemotherapy de-escalation strategy in patients with advanced-stage Hodgkin lymphoma with negative positron emission tomography scan after 2 escalated BEACOPP cycles.

INTRODUCTION Escalated BEACOPP (escBEACOPP: bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) significantly improves overall response rates (ORRs) and prolongs progression‑free survival (PFS) in patients with advanced‑stage Hodgkin lymphoma (HL). However, 6 to 8 cycles of escBEACOPP are associated with increased acute toxicity and late complications. OBJECTIVES We aimed to determine the role of early positron emission tomography-computed tomography (PET‑CT) response assessment in a de‑escalation strategy. PATIENTS AND METHODS We retrospectively analyzed 188 consecutive patients with advanced‑stage HL treated at diagnosis. Patients received 2 cycles of escBEACOPP followed by an early PET‑CT response assessment performed after 2 cycles of chemotherapy (PET2). Patients with an active disease continued therapy with escBEACOPP, while those with negative PET2 were de‑escalated to ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine). Radiotherapy was allowed in patients with stage IIBX. RESULTS PET2 allowed for de‑escalation of therapy in 141 patients (75%). Their ORR was 92.2%, with a complete remission (CR) rate of 91.5%; 10‑year PFS and overall survival (OS) were 87.2% and 95%, respectively. In the whole cohort, ORR was 87.8% (CR, 85.6%), while the 10‑year PFS and OS were 79.3% and 89.4%, respectively. Hematological and thromboembolic complications were significantly more frequent in patients treated with 6 escBEACOPP cycles, including febrile neutropenia (25 patients, [53.2%] vs 7 [5%]), serious anemia (35 [74.5%] vs 11 [7.8%]), or thrombocytopenia (16 [34%] vs 7 [5%]) (P <0.001 for all comparisons with de‑escalation strategy) as well as pulmonary embolism (3 [6.4%] vs 0) (P = 0.02). CONCLUSIONS The early de‑escalation strategy allows for effective treatment of advanced HL, with a comparable efficacy to that of 6 to 8 cycles of escBEACOPP, but with significantly reduced toxicity.

Prognostic Relevance of Neutrophil to Lymphocyte Ratio (NLR) and Lymphocyte to Monocyte Ratio (LMR) in Newly Diagnosed Advanced-Stage Hodgkin Lymphoma Patients Treated up-Front with a PET-2 Risk Adapted Protocol

Background: Hodgkin Lymphoma (HL) is characterized by an inflammatory background and it has been demonstratedthat the reactive myeloid cells may exert an immune suppressive effect that favors progression of disease. The easily measurable NLR, the ratio between absolute neutrophils counts (ANC) and absolute lymphocyte count (ALC) and LMR, the ratio between ALC and absolute monocyte count (AMC) have been reported to reflect both the systemic inflammation and the myeloid associated immune suppression. We previously identified NLR, and to a lesser extend LMR, at baseline, as predictor of progression free survival (PFS) in HL patients.Objectives: To validate NLR>6 and LMR≤2 as predictor of clinical outcome at diagnosis in the context of a prospective clinical trial of newly diagnosed advanced stage (aa) HL patients treated upfront with a PET-2 risk-adapted strategy.Methods: According to HD 0607 trial (Gallamini, JCO 2018), 782 advanced-stage HL patients were treated with 2 ABVD courses and a PET-2 performed afterwards. PET-2 positive (PET-2+) patients (N=149) were randomized to either BEACOPP escalated (Be) plus BEACOPP baseline (Bb) (4+4 courses) or Be+Bb (4+4) and Rituximab. PET-2 negative (PET-2-) patients were treated with 4 additional ABVD and, upon CR achievement, randomized to either consolidation radiotherapy on the sites of initial bulky disease or no further treatment. PET scans were centrally reviewed by an expert panel by Blinded Independent Central Review.Results:Median NLR at baseline was 5.7 (IQ range 3.8-8.3). NLR was higher in younger patients (<45 years, p=0.0005), in females (p=0.0027) and in patients with B symptoms (p<0.0001), bulky disease (>7 cm, p<0.0001) and high IPS (p<0.0001). LMR was lower in males (p=0.01) and in patients with B symptoms (p<0.0001), bulky disease (p<0.0001) and high IPS (≥3, p<0.0001). Neither NLR nor LMR values were associated with Ann Arbor stage. Higher NLR (p=0.0001 and p=0.0003) and lower LMR (p=0.01, and p=0.02) were respectively associated with a PET-2+ (DS score 4 and 5) and failure to achieve long-term disease control. Receiving operator curve (ROC) confirmed 6 as the cut-off of NLR to predict clinical outcome with 59% (95% C.I. 51-68) sensitivity and 57% (95% C.I. 53-61) specificity (AUC 0.59). Negative predictive value of LMR, with cutoff of 2, was 79% with 40% (95% C.I. 31-48) sensitivity and 50% (95% C.I. 46-54) specificity (AUC 0.56). NLR was >6 in 88/149 (59%) PET-2+ and in 269/628 (43%) PET-2- patients. By univariate and multivariate analysis, bulky disease, IPS≥3, NLR>6 were strong independent predictors of early PET-2 response after ABVD (table I). Only PET-2 positivity (p<0.0001) and IPS≥3 (p=0.0001) were independent predictors of PFS by multivariate analysis.Focusing on PET-2 negative patients, we found that patients with NLR>6 had an inferior 3-years PFS compared to patients with NLR ≤6 (84% versus 89%, p=0.003), while there was no stastical difference based on LMR status.Conclusion: At diagnosis, the presence of bulky disease, IPS score ≥3 and NLR>6 are independent predictors of early ABVD response (PET-2 positivity) and this information should be considered when selecting the initial treatment for aaHL patients. [Display omitted] DisclosuresDi Raimondo:Celgene: Honoraria; Takeda: Honoraria, Research Funding. Trentin:Janssen: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria; Gilead: Research Funding. Gallamini:Takeda: Consultancy, Speakers Bureau. Rambaldi:Amgen Inc.: Consultancy; Celgene: Consultancy; Roche: Consultancy; Italfarmaco: Consultancy; Omeros: Consultancy; Pfizer: Consultancy; Novartis: Consultancy.

Metabolic Tumour Volume for Response Prediction in Advanced-Stage Hodgkin Lymphoma.

Rationale: (18F)fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) for staging Hodgkin lymphoma may allow for accurate and reliable assessment of the metabolic tumour volume (MTV) as baseline risk factor. Our aim was to analyse the prognostic impact of MTV measurements, obtained by different means in advanced-stage Hodgkin lymphoma patients treated within the German Hodgkin Study Group HD18 trial. Methods: Within the German Hodgkin Study Group trial HD18, 310 patients underwent 18F-FDG PET/CT scanning for staging which was available to the central review panel for quantitative analysis. We calculated the MTV by four different thresholding methods and performed receiver operating characteristic (ROC) analysis to evaluate the potential for prediction of early response determined by PET after two cycles (PET-2) dose-escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP). Logistic regression was used to evaluate its prognostic value concerning progression-free survival (PFS) and overall survival (OS). Results: All different MTV calculations used predicted PET-2 response to a moderate and comparable degree (area under the curve = 0.62-0.63, P = 0.01-0.06). With none of the measuring methods did the ROC curves point to any unique cut-off values, but indicated a wide range of possible cut-offs. However, none of the MTV measurements was prognostic for PFS (Hazard ratio 1.2-1.5, P = 0.15-0.52) or OS (Hazard ratio 1.0-1.5, P = 0.95 - 0.27). Conclusion: Baseline MTV as determined by different means, is a predictive factor for early response to eBEACOPP after two cycles. However, value as a prognostic factor after highly effective PET-2 adapted treatment strategy could not be observed.

Advanced-Stage Hodgkin Lymphoma in the East of England Cancer Network: A 10-Year Comparative Analysis of Outcomes for Patients Treated with ABVD or Escalated BEACOPP in the Non-Trial Setting Compared with Age-Matched Patients Treated in the Multinational RATHL Trial

Introduction: The majority of young patients presenting with advanced-stage Hodgkin lymphoma (HL) in the UK are managed with ABVD. However, from 2009, escalated BEACOPP (escBEACOPP) was introduced as a treatment option in certain UK cancer centres. Within the East of England Cancer Network (EECN), 6 hospitals introduced escBEACOPP as a treatment option, while 2 hospitals continued to use ABVD as standard first-line therapy for all patients. During this time period, recruitment to the RATHL (Response Adjusted Therapy for Hodgkin Lymphoma) trial was also a first-line treatment option across the UK and 4 of the EECN centres. Analysing data from all patients treated in the EECN centres and the RATHL trial has therefore enabled outcomes of patients treated with either escBEACOPP or ABVD within a non-trial setting to be compared to patients treated with ABVD in a clinical trial.Methods: We performed a retrospective multicentre analysis of patients treated for advanced-stage HL, aged 16-59 years, diagnosed between 2004-2014 in the EECN and compared outcomes with age and international prognostic score (IPS)-matched patients in the RATHL trial.Results: Over this 10-year period, 250 patients were diagnosed with advanced-stage HL in the EECN; 202 commenced treatment with ABVD (23 within RATHL), 44 escBEACOPP, 3 other regimens, and 1 died before treatment. Five-year progression-free survival (PFS) for all patients was 82% and overall survival (OS) was 93%. In RATHL, 1088 patients aged 18-59 years commenced treatment with ABVD, with 5-year PFS of 81% and OS of 95%. Within the EECN, there was a clinician-patient preference to treat higher-risk patients (IPS 3+) with more intensive therapy; a higher proportion of escBEACOPP patients were IPS 3+ (IPS 3+: escBEACOPP 75% vs. ABVD 39%, p<0.0001).ABVD-treated EECN patients had highly similar 5-year PFS and OS rates compared with age-matched RATHL patients (PFS 80% vs 81%; HR: 1.1 (95% CI: 0.8-1.5), p=0.60: OS 93% vs 95%; HR: 1.5 (95% CI: 0.8-2.7), p=0.21; Figure 1A-B). Despite being enriched with higher-risk patients, the 5-year PFS for all escBEACOPP-treated EECN patients was superior to ABVD in both the EECN and RATHL cohorts (PFS 95% vs 80% (EECN); HR 0.2 (95% CI: 0.1-0.9), p=0.04; Figure 1C; Table 1), but there was no significant OS advantage (5-year OS 97% vs. 93% (EECN); HR 0.4 (95% CI: 0.0-2.8), p=0.34; Figure 1D; Table 1). However, subgroup analysis of higher-risk (IPS 3+) patients found that escBEACOPP-treated EECN patients had both a 5-year PFS and OS advantage when compared with IPS 3+ ABVD-treated EECN patients (PFS 97% vs 74%; HR 0.1 (95% CI: 0.0-0.8), p=0.03; OS 100% vs 85%; p=0.03). However, when these higher-risk escBEACOPP patients were compared with IPS 3+ patients from RATHL, the significance of the OS advantage was lost (Table 1).Despite similar relapse/refractory rates for IPS 3+ ABVD-treated patients in the EECN and RATHL datasets, the OS for relapsed/refractory patients was inferior in the EECN. One explanation could be the time period over which the EECN data was collected, as the majority (7/9) of higher-risk ABVD-treated EECN patients who died from progressive disease died prior to 2011, when brentuximab vedotin was unavailable to treat relapsed HL in the UK.Conclusion: Our data support recently published European data showing that first-line HL patients treated in the non-trial setting achieve similar outcomes to those treated in contemporary clinical trials. Our data also reflect prospective trial results which show a first-remission PFS, but not OS, advantage for advanced-stage HL patients treated with escBEACOPP compared with ABVD, but suggest that higher-risk patients might benefit disproportionately from more intensive first-line therapy with escBEACOPP. However, improved access to more effective salvage treatments for relapsed/refractory patients may have diminished any OS benefit from the use of first-line escBEACOPP in higher-risk patients. [Display omitted] DisclosuresFollows:Abbvie: Other: advisory board and lecturing; Janssen: Other: advisory board and lecturing; Gilead: Other: advisory board and lecturing; Roche: Other: advisory board and lecturing.

Prognostic Value of Bone Marrow Tracer Uptake Pattern in Baseline PET Scans in Hodgkin Lymphoma: Results from an International Collaborative Study.

PET/CT-ascertained bone marrow involvement (BMI) constitutes the single most important reason for upstaging by PET/CT in Hodgkin lymphoma (HL). However, BMI assessment in PET/CT can be challenging. This study analyzed the clinicopathologic correlations and prognostic meaning of different patterns of bone marrow (BM) 18F-FDG uptake in HL. Methods: One hundred eighty newly diagnosed early unfavorable and advanced-stage HL patients, all scanned at baseline and after 2 adriamycin-bleomycin-vinblastine-dacarbazine (ABVD) courses with 18F-FDG PET, enrolled in 2 international studies aimed at assessing the role of interim PET scanning in HL, were retrospectively included. Patients were treated with ABVD × 4-6 cycles and involved-field radiation when needed, and no treatment adaptation on interim PET scanning was allowed. Two masked reviewers independently reported the scans. Results: Thirty-eight patients (21.1%) had focal lesions (fPET+), 10 of them with a single (unifocal) and 28 with multiple (multifocal) BM lesions. Fifty-three patients (29.4%) had pure strong (>liver) diffuse uptake (dPET+) and 89 (48.4%) showed no or faint (≤liver) BM uptake (nPET+). BM biopsy was positive in 6 of 38 patients (15.7%) for fPET+, in 1 of 53 (1.9%) for dPET+, and in 5 of 89 (5.6%) for nPET+ dPET+ was correlated with younger age, higher frequency of bulky disease, lower hemoglobin levels, higher leukocyte counts, and similar diffuse uptake in the spleen. Patients with pure dPET+ had a 3-y progression-free survival identical to patients without any 18F-FDG uptake (82.9% and 82.2%, respectively, P = 0.918). However, patients with fPET+ (either unifocal or multifocal) had a 3-y progression-free survival significantly inferior to patients with dPET+ and nPET+ (66.7% and 82.5%, respectively, P = 0.03). The κ values for interobserver agreement were 0.84 for focal uptake and 0.78 for diffuse uptake. Conclusion: We confirmed that 18F-FDG PET scanning is a reliable tool for BMI assessment in HL, and BM biopsy is no longer needed for routine staging. Moreover, the interobserver agreement for BMI in this study proved excellent and only focal 18F-FDG BM uptake should be considered as a harbinger of HL.