Advanced HL Research Articles

Stage-adapted treatment of HIV-associated Hodgkin lymphoma: Long-term results of a prospective, multicenter study.

Results of a prospective study of stage-adapted treatment of humanimmunodeficiency virus (HIV)-associated Hodgkin lymphoma (HIV-HL) showed a 2-year overall survival (OS) of 90.7% with no significant difference between early favorable (EF), early unfavorable (EU), and advanced HL. Patients with EF HIV-HL received two to four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) + 30 Gy involved field (IF) radiation, those with EU HIV-HL received four cycles of ABVD or BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) baseline + 30 Gy IF, and six to eight cycles of BEACOPP baseline were administered in advanced disease. The objective of the present analysis is to determine long-term outcomes of HIV-HL. Of 108 patients, 23 (21%) had EF HL, 14 (13%) had EU HL, and 71 (66%) had advanced-stage HL. After a median follow-up of 9.14 (range, 0-12.9) years, there were five primary refractory HL patients (5%) and 11 relapses (10%), of which seven were late relapses (>2 years). A second primary malignancy (SPM) occurred in 10 patients after a median of 7.3 years (range, 1.5-10.7) from HL diagnosis. The 10-year OS for patients with EF, EU, and advanced HL was 95.7%, 84.6%, and 76.1%, respectively. By multivariate analysis, Center for Disease Control and Prevention category C (hazard ratio [HR]3.00, 95% confidence interval [CI]:1.16-7.74, p = 0.023) and achievement of complete remission were significant for OS (HR 0.03, 95% CI: 0.01-0.08, p = 2.45 × 10-9). In conclusion, a stage-adapted treatment approach for HIV-HL is highly effective with long-term survival rates similar to those reported in HIV-uninfected HL. However, the risk for late relapse and SPM is significant.

P025: RADAR: An international phase III, PET response-adapted, randomised trial in progress, comparing ABVD±ISRT with brentuximab vedotin+AVD±ISRT in patients with previously untreated limited-stage classical Hodgkin lymphoma

Figure 1: RADAR trial schema Background: Limited-stage classical Hodgkin lymphoma (lsHL), stages I or II without B-symptoms or mediastinal bulk disease, has excellent long-term survival (≥90%) with modern treatment. Commonly used approaches, based on GSHG and EORTC trials, include 2–4 cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) plus 20 or 30 Gy radiotherapy (RT), but there are concerns about the impact of using RT in all patients (pts) on the incidence of 2nd cancers and cardiovascular disease. In the UK NCRI RAPID trial, pts who had a -ve PET scan after 3 cycles of ABVD were randomised between RT and no RT; outcomes in the no RT arm were very good but the non-inferiority margin of -7% was not achieved. The RADAR trial is building on the PET-adapted approach of RAPID but intending to make the chemotherapy more effective by replacing bleomycin with the CD30 targeted antibody drug conjugate, brentuximab vedotin (BV), in the BV+AVD regimen. Early phase trials of BV+AVD in lsHL and the phase III ECHELON-1 trial in advanced HL have demonstrated its efficacy and safety. In addition, RT will be integrated on an individualised basis to pts in RADAR who are PET -ve after initial chemotherapy but with larger nodal masses at baseline. Methods: RADAR comprises 2 parallel identical phase III randomised multicentre trials in the UK, Europe, Australia, New Zealand (trial 1; 642 pts), Canada and the USA (trial 2; 400 pts). Eligibility: age 16–69 years, previously untreated stage IA/IIA HL above the diaphragm, any mediastinal mass ≤0.33 of internal thoracic diameter, informed consent. Pts will be randomised to receive either ABVD or BV+AVD. A centrally-reviewed PET-CT scan after cycle 2 (PET2) will determine further treatment (Deauville score (DS) 1–3: total 3 cycles +/- individualised RT; DS 4: total 4 cycles + 30 Gy ISRT; DS 5: treatment failure, subsequent treatment of clinician’s choice). 1y endpoint is progression free survival (PFS) and the trial will have 85% power to show an improvement from 90 to 95% PFS at 3 years (HR of 0.49) with 2-sided 5% alpha. 2y endpoints are CMR rate at PET2, event-free survival (progression, death, PET2 DS 4–5), OS, safety and toxicity including cardiovascular disease and second cancers. Exploratory endpoints: predictive value of PET after 1 cycle, prognostic value of baseline metabolic tumour volume. Embedded translational research aims to identify biomarkers predictive of treatment failure. RADAR opened to recruitment in April 2022.

Tumor Associated Macrophages and Topoisomerase II Alpha As Prognostic Factors in Advanced Stage Hodgkin's Lymphoma

Background : Classic Hodgkin's lymphoma (cHL) is associated with a high cure rate, but approximately 20% of patients are refractory to initial treatment and 10-30% of patients will relapse after achieving complete remission (CR) , the search of new prognostic factors to identify these high risk patients remains challenging in daily practice, the aim of this study is to evaluate CD68 positive Tumor associated macrophages(TAM) and the cell proliferation marker topoisomerase II alpha as prognostic factor in advanced stage (cHL). Patient and Methods: This study included 82 patients with Advanced stage classic Hodgkin lymphoma presented to Medical Oncology Departments of the National Cancer Institute, Cairo University and Zagazig University hospitals in the period from 2012 to 2017. All patients received ABVD regimen as induction. Immunohistochemical (IHC) analysis was performed for all cases using Tissue microarrays (TMAs) sections and stained with anti‐ CD68 (clones KP1 and PGM1, Dako, Glostrup,Denmark). For Topo II testing, IHC staining was performed on deparaffinized sections using the avidin-biotin complex immunoperoxidase technique with separate antibodies recognizing CD30 and the isoform of Topo II. The percentage of cells expressing cytoplasmic CD30 and nuclear Topo II staining simultaneously was determined for each case. We examined four cutoff points of CD68 expression (<= 20% versus >20%), <5% low (score 1), 5-15% intermediate (score 2) & > 15% high (score 3), <5% low (score 1), 5-25% intermediate (score 2) & > 25% high (score 3) and <= 50% versus > 50%. For Topo II expression, two cut off points were analyzed (<= 30% versus >30%) and (<= 75% versus >75%). Results: The study included 41 males and 41 females with a ratio of 1: 1. The median age was 30.5 years (range: 18-60 years). CRwas achieved in 64.6% (53/82 of patients) and 35.4% of all patients (29/82) were refractory. Relapse was reported in17% of the CR cases (9/53). The significant statistical difference in disease-free survival (DFS) for CD68+was observed at a cut off value of 50%, where 60 patients had CD68 <= 50% and 22 patients had CD68 >50%. The mean DFS for patients with CD68 <= 50% was 49.33 months ± 2.18 months (confidence interval: 45.05 to 53.60 months) vs. 35.255 ± 4.94 months (confidence interval: 25.55 to 44.95 months) in patients with CD68 > 50% (p = 0.015). The low CD68 group included more patients in CR (67.9%, n=36 vs. 32.1%, n=17) , male to female ratio was equal(1:1) in both groups (<= 50% ,n=30:30) and (> 50% ,n=11:11), B symptoms also was equal in both groups (<= 50% , 81% ,n=49) and (> 50% 81% ,n=18), patients with CD68<= 50% had more extra nodal disease (22%, n=13 vs. 18%, n=4) and also more bulky disease (20%, n=12 vs. 4.5% n=1) compared with high (CD68>50%) group. The overall survival (OS) was not significant for all CD68 cutoff points. Higher CD68 is associated with decreased OS: 48 vs. 52 month (CI: 42 to 53 month, p=0.42) at cut off 50%. Topo II expression using the two cut off points was not statistically significant in relation to both DFS and OS , the higher topoII group included more patients in CR (80% ,n=42 topo II >30% vs. 20%, n=10 topo II<=30%) also,(67%, n=53 Topo II >= 75% vs. 33%, n=17 Topo II < 75%). Higher Topo II is associated with prolonged DFS (45 months vs. 36 month) confidence intervals: 40 to 50 months vs 27 to 46. Months) at cut off 30% (p=0.8). At cutoff 75%, the DFS was 46 vs. 38 months (Confidence intervals: 41.73 to 52.10 months vs. 30 to 47.7 months, p= 0.36). Higher Topo II is associated with decreased OS: 50 vs.54 months (CI: 46 to 54 month) at cutoff 75% (p=0.19). CD68 was only statistically significant in correlation to patient age (p = 0.05), and non significant to serum albumin ,hemoglobin level , white blood cells count ,international prognostic score (IPS). Topo II was not statistically significant with the previous patient characteristics. Conclusion : High level of CD68 expression in patients with advanced stage HL (>50%) was significantly associated with inferior DFS but not OS, Topo II does not have significant prognostic value in relation to both DFS or OS of advanced HL cases. DisclosuresNo relevant conflicts of interest to declare.

Brentuximab Vedotin Plus Doxorubicin, Vinblastine, Dacarbazine (A+AVD) As Frontline Therapy Demonstrates Superior Modified Progression-Free Survival Versus ABVD in Patients with Previously Untreated Stage III or IV Hodgkin Lymphoma (HL): The Phase 3 Echelon-1 Study

Brentuximab Vedotin Plus Doxorubicin, Vinblastine, Dacarbazine (A+AVD) As Frontline Therapy Demonstrates Superior Modified Progression-Free Survival Versus ABVD in Patients with Previously Untreated Stage III or IV Hodgkin Lymphoma (HL): The Phase 3 Echelon-1 Study

Phase II trial of GVDexa (gemcitabine, vinorelbine and dexamethasone) regimen in relapsed/refractory Hodgkin’s lymphoma.

e19519 Background: Gemcitabine, vinorelbine and liposomal doxorubicin (GVD) is an effective regimen in relapsed/refractory Hodgkin’s lymphoma (RRHL). Conventional second-line chemotherapy is still required as the cost of immunotherapy and antibody-drug conjugates are prohibitive to Indian patients. We report the results of a phase II, open-label, single-arm, single centre interventional study in RRHL where dexamethasone replaced liposomal doxorubicin. Methods: Adult patients (≥18 years) with RRHL at first or second relapse were included. GVDex was delivered as outpatient once in 3 weeks (Gemcitabine 1000 mg/m2 IV over 30 min on D1,8; Vinblastine 25 mg/m2 IV fast infusion on D1,8; Dexamethasone 40 mg PO D1-4) for two cycles followed by interim PET CT assessment by Cheson’s criteria and Deauville scoring. The primary endpoint was the objective response rate (ORR = complete response + partial response). The sample size was calculated using Fleming’s 2-stage model (α error: 0.05 and power: 0.8). Twenty patients were required in the first stage. If there were ≥16 responses, the null hypothesis would be rejected and the study stopped. Results: Between May 2016, and December 2020, 26 patients with RRHL were screened, and 20 were enrolled: primary resistant HL-8 patients (40%) and relapsed HL- 12 patients (60%). The median age was 35 years (range:20-52). Six patients (30%) presented with limited stage and 14 patients (70%) with advanced stage HL at relapse. GVdex was delivered as a first salvage regimen in 18 patients (90%) and second in 2 patients. After 2 cycles of GVDex, 16 (80%) had responded [partial response: 12 (60%); complete response: 4 (20%)]. Median number of cycles of GVDex: 3 (range: 1-4). Five patients (25%) required dose reductions due to chemotherapy-related toxicities. The median duration of objective response was 13.4 months. Eleven patients (55%) underwent high-dose chemotherapy supported by autologous stem cell rescue. After a median follow-up of 25 months (95% CI: 5.9-44.5), the median progression-free survival (PFS) was 24.7 months, and the median overall survival (OS) has not been reached. The estimated 2-year PFS was 44%, and the 2-year OS was 79%. The most common treatment-related adverse events were anemia (100%), neutropenia (70%, 14/20) and fatigue (70%, 14/20). Grade 3 or 4 treatment-related AEs occurred in 14 patients (70%). Grade ≥3 neutropenia occurred in 9 patients (45%) and febrile neutropenia in 3 patients (15%). Serious adverse events were reported in 3 patients (15%). One patient developed Ficat and Arlet classification stage III avascular necrosis of the femoral head. One patient died due to suspected COVID-19 pneumonia (non-neutropenic fever) before cycle 2 of chemotherapy. Conclusions: GVDex it is an effective salvage regimen with acceptable toxicity in patients with RRHL. Clinical trial information: CTRI/2017/04/008361.

Prognostication for Advanced Stage Hodgkin Lymphoma (HL) in the Modern Era: A Project from the Hodgkin Lymphoma International Study for Individual Care (HoLISTIC) Consortium

Prognostication for Advanced Stage Hodgkin Lymphoma (HL) in the Modern Era: A Project from the Hodgkin Lymphoma International Study for Individual Care (HoLISTIC) Consortium

Abstract IA09: Genomics of common AYA lymphomas: Hodgkin lymphoma and primary mediastinal B-cell lymphoma

Abstract Hodgkin lymphoma (HL) and primary mediastinal B-cell lymphoma (PMBCL) are both B-cell malignancies that commonly arise in the mediastinum and have a peak incidence in the adolescent and young adult (AYA) age range of 15-39y. Advances in sequencing technology with low-input samples have allowed for recent advances in our knowledge of the key molecular alterations in these lymphoma subtypes. In this session, we will discuss the unique genomic features of HL and PMBCL and highlight what is known about differences across the age spectrum. We will also discuss how genomics can inform the use of novel therapies for HL and PMBCL. Hodgkin lymphoma has traditionally been challenging to study by standard genomic platforms given the rarity of the Hodgkin Reed Sternberg (HRS) cell among the extensive inflammatory infiltrate. Recently, our group and others have utilized flow cytometry to sort HRS cells and intratumoral T and B cells for genomic analyses. Optimization of library preparation for ultralow (&amp;lt;5ng) input now allows for whole-exome characterization of classical HL. Sequencing of the first 10 HL exomes revealed inactivating mutations in β-2-microglobulin (B2M) in 7 of 10 cases. B2M alterations resulted in loss of MHC Class I expression, providing a potential mechanism of HRS cell immune escape (Reichel et al., Blood 2015). Other common alterations observed in this cohort were TNFAIP3 (in 6/10 cases) and HISTH1E (5/10 cases). More recently, a larger cohort of 23 cases of cHL was evaluated by whole-exome sequencing (Wienand et al., Blood Advances 2019). Here the most frequent alterations occurred in B2M (39%), NFKNIE (26%), and TNFAIP3 (26%). Further analysis of this cohort integrating genomic mutations, somatic copy number alterations, and structural variants identified key pathways that are altered in cHL including genomic mechanisms of immune evasion, enhanced JAK/STAT signaling, and alterations in NF-κB signaling. It is not known if differences in genomic alterations exist across the age spectrum in cHL and how this might guide therapy. For example, loss of B2M is associated with younger/AYA age range (median age of B2M negative (altered) vs. positive = 30y vs. 47y, p&amp;lt;0.001). Further studies are needed to fully characterize the HL genome and understand the implications of alterations for therapy in both pediatric and adult cohorts. Primary mediastinal B-cell lymphoma is a rare subtype of non-Hodgkin lymphoma, accounting for 2% to 3% of NHL. The disease typically presents as a large mediastinal mass in patients in the AYA age range, with an increased incidence in females. Although previously considered a subtype of diffuse large B-cell lymphoma, PMBCL is now recognized as its own clinical and molecular/pathologic entity that shares many similarities with Hodgkin lymphoma. Recent genomic characterization of PMBCL has been performed using whole-exome sequencing (Mottok et al., Blood 2019; Chapuy et al., Blood 2019). These studies reported recurrent alterations in components of JAK/STAT and NF-κB signaling as well as genetic mechanisms of immune evasion similar to that observed in cHL including alterations in B2M, CD274, and CIITA. In addition, cases were observed to have high tumor mutational burden and an apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) mutation signature, which may confer sensitivity to PD-1 blockade. In summary, recent genomic findings in HL and PMBCL demonstrate molecular similarities between these lymphoma subtypes and define the genetic basis for immune evasion sensitivity to PD-1 blockade. This has translated to national clinical trials for AYAs with HL and PMBCL. A randomized phase III trial of nivolumab + AVD vs. brentuximab + AVD for children and adults with advanced stage HL is currently ongoing (NCT03907488). In PMBCL, a randomized phase III trial evaluating nivolumab in combination with standard therapy for upfront disease is in development and will include pediatric and adult patients across NCTN sites. Citation Format: Lisa G. Giulino-Roth. Genomics of common AYA lymphomas: Hodgkin lymphoma and primary mediastinal B-cell lymphoma [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr IA09.

Older Patients (pts) with Previously Untreated Classical Hodgkin Lymphoma (cHL): A Detailed Analysis from the Phase 3 ECHELON-1 Study

Older Patients (pts) with Previously Untreated Classical Hodgkin Lymphoma (cHL): A Detailed Analysis from the Phase 3 ECHELON-1 Study

Lymphoma Virome Dynamics Revealed By Cell-Free DNA Sequencing

Lymphoma Virome Dynamics Revealed By Cell-Free DNA Sequencing

Combining Biology and Chemistry for a New Take on Chemotherapy: Antibody-Drug Conjugates in Hematologic Malignancies.

This review is about the antibody-drug conjugate (ADC), a form of drug delivery consisting of a monoclonal antibody, linker, and cytotoxic payload. We summarize the history of ADC development, highlighting the three FDA-approved ADCs currently available. Gemtuzumab ozogamicin is a CD33-targeted ADC linked to calicheamicin. It is approved for CD33+ AML in the first line or the relapsed or refractory (R/R) setting. Brentuximab vedotin is a CD30-targeted ADC bound to MMAE. It is approved for the treatment of certain R/R CD30+ lymphomas. Recently, it has been approved for first line therapy with chemotherapy in advanced HL. Inotuzumab ozogamicin is a CD22-directed ADC attached to calicheamicin indicated for the treatment of adults with R/R B cell precursor ALL. Three ADCs have been approved for the treatment of various hematologic malignancies. We discuss the pertinent human trials that led to FDA approval. We include our perspectives about drug resistance, toxicities, and future development.

Mood Selection in Relative Clauses by French–Spanish Bilinguals: Contrasts and Similarities between L2 and Heritage Speakers

In this paper, we explore three issues related to the acquisition of mood selection in Spanish relative clauses by second language (L2) and heritage (HL) speakers of Spanish: (1) whether HL speakers are more native-like than L2 learners; (2) whether the speakers’ performance differs depending on task modality (written vs. oral), since HL speakers are known to perform better in oral tasks and L2 learners tend to do better in written tasks; and (3) whether knowledge of French as an L1/dominant language (DL) has an impact on the acquisition of Spanish subjunctive, since both languages include this mood in their grammars, but it is used more productively in Spanish. Results from a sentence combination felicity task (SCFT) in Spanish—in written and oral forms—and a written elicited production task (EPT) in French, administered to advanced L2 and HL speakers of Spanish whose L1/DL is French and two monolingual (Spanish and French) control groups, revealed that L2 learners pattern more closely with the control group than HL speakers in the SCFT, both written and orally. In the EPT, all bilingual speakers display higher levels of subjunctive use than the control group, showing a potential influence from the L2/weaker language on the L1/DL.

Randomized phase III study comparing an early PET driven treatment de-escalation to a not PET-monitored strategy in patients with advanced stages Hodgkin lymphoma: Final analysis of the AHL2011 LYSA study.

7503Background: Escalated BEACOPP (BEA) improves PFS but not OS in pts with advanced HL compared to ABVD and is associated to a higher risk of hematological toxicity, secondary leukemia and inferti...

Improving outcomes with brentuximab vedotin (BV) plus chemotherapy in patients with newly diagnosed advanced stage Hodgkin lymphoma.

7534Background: ECHELON-1 is a phase 3 study of BV plus doxorubicin, vinblastine, and dacarbazine (A+AVD) vs ABVD as frontline therapy in untreated advanced HL (NCT01712490). G-CSF primary prophyla...

Better outcome with haploidentical over HLA-matched related donors in patients with Hodgkin's lymphoma undergoing allogeneic haematopoietic cell transplantation-a study by the Francophone Society of Bone Marrow Transplantation and Cellular Therapy.

The question of the best donor type between haploidentical (HAPLO) and matched-related donors (MRD) for patients with advanced HL receiving an allogeneic hematopoietic cell transplantation (allo-HCT) is still debated. Given the lack of data comparing these two types of donor in the setting of non-myeloablative (NMA) or reduced-intensity (RIC) allo-HCT, we performed a multicentre retrospective study using graft-vs.-host disease-free relapse-free survival (GRFS) as our primary endpoint. We analysed the data of 151 consecutive HL patients who underwent NMA or RIC allo-HCT from a HAPLO (N = 61) or MRD (N = 90) between January 2011 and January 2016. GRFS was defined as the probability of being alive without evidence of relapse, grade 3-4 acute GVHD or chronic GVHD. In multivariable analysis, MRD donors were independently associated with lower GRFS compared to HAPLO donors (HR = 2.95, P < 0.001). Disease status at transplant other than CR was also associated with lower GRFS in multivariable analysis (HR = 1.74, P = 0.01). In addition, the administration of ATG was independently linked to higher GRFS (HR = 0.52, P = 0.009). In summary, we observed significantly higher GRFS in HL patients receiving an allo-HCT using the HAPLO PT-Cy platform compared to MRD.

Prognostic Value of Interim Positron Emission Tomography Among Children with Advanced Hodgkin Lymphoma in Developing Countries: Children Cancer Hospital Egypt Experience

Rationale and aim of the study: This is a retrospective, single center study was done to assess the prognostic role of 'interim' positron emission tomography (PET) performed during treatment of advanced stages HL with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) in pediatric patients.Patients and methods: Three hundred and eighty one patients with newly diagnosed Hodgkin lymphoma were enrolled. One hundred sixty five patients with early unfavorable and 216 with advanced-stage disease were treated with ABVD ± involved-field radiotherapy (IFR). PET scan was performed at baseline and after two cycles of chemotherapy. Treatment was not changed according to the results of the interim scan. PET scans reports was used using the Deauville five-point scale, blinded to treatment outcome.Results:Eighty-seven scans out of 336 were scored as positive (17.3%) and 249 (82.7%) as negative. The 5- years overall survival (OS) was 94% (95% Confidence Interval (CI) :91.5 Ð 96.6) for the whole study population, 86.2% (95% CI :78.3 - 94) for patients with interim positive scans and 97% (95% CI:94.2 - 99.3) for patients with interim negative scans (P<0.0001) [Figure:1].The 5-year Event-free survival (EFS) rate was 80% (95% CI :74.3 Ð 84.4) for the whole study population, 63.2% (95% CI :48.6 Ð 77.4) for patients with interim positive scans and 82.6% (95% CI :76.3 Ð 88.8) for patients with interim negative scans (P<0.0001) [Figure:2].In conclusion: The prognostic role and validity of using the interim PET scan response have been confirmed to be strongly related to treatment outcome by the present study. These results confirm that ABVD with or without IFR is an adequate treatment for more than 70% of pediatrics patients in advanced stages HL. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Approach and Feasibility of Patient-Reported Outcomes (PROs) in a Phase III Clinical Trial for Advanced Stage Classical Hodgkin Lymphoma (cHL) in Children and Adolescents

Introduction: Given the high cure rates in classical Hodgkin lymphoma (cHL) with conventional therapy, careful consideration of the economics of newer agents should be considered. We describe the feasibility of embedding Patient-Reported Outcomes (PROs) for chemotherapy-induced peripheral neuropathy (CIPN) and cost effectiveness (CEA) in a randomized, multi-institutional Phase III study [NCT02166463; Children's Oncology Group (COG) AHOD1331], evaluating the efficacy of the novel agent, Brentuximab vedotin, for advanced cHL in children and adolescents.Methods: Recruitment for PROs of interest is targeted for 250 of the planned 600 trial participants. Participation in the trial includes prospective collection of patient- and parent proxy-reported outcomes. CIPN is evaluated with the 11-item FACT-GOG-NTX and paired with the 9-item CHRIs-Global to serially evaluate health-related quality of life (HRQL) consequences of CIPN from initial diagnosis to 12 months off therapy. For CEA, US-based participants are queried from diagnosis through 36 months off therapy with the 4-item Stanford Healthcare Utilization Questionnaire (parent-report), the Health Utilities Index (HUI) 2/3, and the 23-item Caregiver Work Limitations Questionnaire (parent-report) as a measure of productivity loss. A study-designated research assistant is charged with contacting site personnel at study entry and at each scheduled assessment. All data are uploaded into a web-based relational database for future analysis. Units of healthcare utilization from the Stanford Healthcare Utilization measure and adverse events (AE) requiring hospitalization will be monetized with unit costs from US-based administrative databases, including the US National Inpatient Sample (NIS) and Kids' Inpatient Database (KID), Massachusetts All-Payer Claims Database (APCD) and Medicare, based on site of care and diagnostic and/or procedure codes. Data on severe AE from the two predecessor trials (COG AHOD 0031 and AHOD 0831) will be monetized as a training exercise. Total costs will be calculated by study arm and will include monetization of significant adverse events and health care utilization and will be expressed as cost per quality-adjusted life year derived from the HUI.Results: The clinical trial, activated in March 2015, has enrolled 161 participants; accrual is ongoing at 172 participating institutions. 156 participants (>95%) have completed the baseline CIPN and CEA measures. Among participants who have completed the baseline CIPN and CEA assessments, 90% have completed subsequent measures. Monetization of significant adverse events and utilization is in progress.Conclusion: We demonstrate a feasible approach evidenced by high completion rates of assessments for prospective evaluation of CIPN, HRQL, and healthcare utilization in a multi-institutional trial of children with advanced HL. Our experience serves as a proof of principle to cooperative groups regarding the resources and the feasibility of incorporating necessary PRO and health utilization outcomes into Phase III clinical trials as a component of cancer care delivery research. DisclosuresHenderson:Seattle Genetics: Research Funding.

Suicide in European Hodgkin Lymphoma Patients

▪INTRODUCTIONA cohort study from the United States showed that Hodgkin Lymphoma patients in the SEER database had more than two times the risk of suicide compared to the general US population (J Clin Oncol 2008 26:4731-38). However, the risk of suicide in Hodgkin Lymphoma has not been studied in European clinical trial patients where treatment and disease specific information was available.METHODSPatients from the German Hodgkin Study Group (GHSG) HD7 through HD15 studies were analyzed to identify those patients with Hodgkin Lymphoma whose cause of death was suicide. 12,201 patients from Germany, Switzerland, the Netherlands, the Czech Republic, and Austria were included in the analysis of the GHSG HD7-HD15 studies between 1993 and 2009. Median follow-up in these studies was 67.6 months or 5.63 years. Standardized mortality ratio (SMR) for death from suicide was calculated using the general European population as a control. Suicide as a cause of death was compared to other causes of death in the HD7-HD15 studies. Data from other European HL studies was planned to be included but not available at time of submission.RESULTS19 patients (17 males and 2 females) died by suicide in the HD7-HD15 studies during a total observation time of 68,638 person-years, equivalent to 27.7/100,000 person-years. When compared to the suicide rate in the general European population of 12.3/100,000 person-years (Eurostat Statistics Database 2010), the standardized mortality ratio (SMR) in this cohort was 2.25 (95% CI, 1.40 to 3.45) and statistically significant (p=0.0017).Male gender is an established risk factor for suicide in the general population. Male and female suicide rates in the general European population were 20.7/100,000 and 4.7/100,000 person-years (Eurostat 2010) respectively. Male European HD7-HD15 patients had a suicide rate of 43.9/100,000 person-years with a SMR 2.12 (95% CI, 1.28 to 3.33), p=0.0054. Female European HD7-HD15 clinical trial patients had a suicide rate of 6.7/100,000 person-years with a SMR 1.43 (95% CI, 0.24 to 4.72), p=0.575.Median age at diagnosis was 38 years (range 19-59) for the HL patients with suicide. Median time interval between diagnosis of HL and suicide was 42 months (range 1-142), and median age at time of suicide was 46 years (range 22-59). Nodular sclerosis (58%) and mixed cellularity (26%) were the most common HL histologic subtypes in patients with suicide. As defined by the GHSG, advanced stage HL (42%) was the most common in suicide followed by early stage favorable (37%) and early stage unfavorable (21%).74% of HL patients with suicide received radiation therapy at a median dose of 30 Gy, with 58% receiving involved-field radiation therapy (IFRT) and 16% extended-field radiation therapy (EFRT). All patients with suicide received chemotherapy (median 4 cycles), with ABVD (32%), COPP/ABVD (16%), escalated-dose BEACOPP (16%), and escalated-dose followed by baseline-dose BEACOPP (16%) as the most common regimens.17 of 19 patients (90%) were in remission with no evidence of progression or relapsed HL at time of suicide. One patient developed a secondary malignancy (melanoma) prior to death from suicide. There were a total of 818 deaths (6.7%) in the 12,201 patients analyzed in the HD7-HD15 studies. Suicide (2.3%) was the fifth most common cause of death after Hodgkin Lymphoma (29.6%), toxicity from treatment (primary, salvage, and infection = 24.8%), secondary malignancy (21.1%), and cardiopulmonary causes (10.1%). Figure 1.CONCLUSIONSHodgkin Lymphoma patients treated within clinical trials in Europe have greater than twice the incidence of suicide, SMR 2.25, compared to the general population. This is similar to the SMR 2.07 reported in HL patients from the SEER database in the United States. This increase in suicide incidence is in spite of the excellent prognosis in HL, as evidenced by the 90% of patients who were in remission at time of suicide. Male European HL clinical trial patients had over twice the risk of suicide compared to males in the general population, but there was no statistically significant difference found in female European HL patients. With HL occurring most frequently in age groups with a high risk of suicide, clinicians must be vigilant about suicide as a significant cause of death in these patients. [Display omitted] DisclosuresEngert:Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding. LaCasce:Seattle Genetics: Research Funding; Forty Seven Inc.: Consultancy.

Prognostic factors of advanced Hodgkin’s lymphoma: multivariate analysis of 199 Chinese patients with long-term follow-up.

e19021Background: About 30% of advanced HL patients will suffer relapse and some may be overtreated. More accurate methods are needed to identify patients with different prognosis. The current Inte...

Busulfan-based reduced intensity conditioning regimens for haploidentical transplantation in relapsed/refractory Hodgkin lymphoma: Spanish multicenter experience.

Relapsed or refractory Hodgkin lymphoma (advanced HL) still remains a therapeutic challenge. Recently, unmanipulated haploidentical related donor transplant with reduced conditioning regimen (HAPLO-RIC) and post-transplant cyclophosphamide (PT-Cy) as GvHD prophylaxis has became a promising rescue strategy potentially available to almost every patient. This paper reports our multicenter experience using an IV busulfan-based HAPLO-RIC regimen and PT-Cy in the treatment of 43 patients with advanced HL. Engraftment occurred in 42 patients (97.5%), with a median time to neutrophil and platelet recovery of 18 and 26 days. Cumulative incidences of grades II-IV acute GvHD and chronic GvHD were 39% and 19%, respectively. With a median follow-up of 25.5 months for survivors, 27 patients are alive, with 22 of them disease free. Cumulative incidences of 1-year non-relapse mortality and relapse at 2 years were 21% and 24%, respectively. The estimated 2-year event-free survival (EFS) and overall survival (OS) were 48% and 58%, respectively. CR prior to HAPLO-RIC correlated with better EFS (78.5% vs 33.5%; P=0.015) and OS (86% vs 46%; P=0.044). Our findings further confirm prior reports using HAPLO-RIC in advanced HL in a multicenter approach employing an IV busulfan-based conditioning regimen.

Risk-Adapted Treatment of Advanced Hodgkin Lymphoma With PET-CT.

Although patients with advanced-stage classic Hodgkin lymphoma have excellent outcomes with contemporary therapy, the outcomes of patients with refractory disease is suboptimal. Identification of these high-risk patients at diagnosis is challenging as the differences in outcomes using clinical criteria are less marked using current modern therapy. Data suggest that an interim PET-CT may be a powerful tool in risk-stratifying patients. Retrospective studies show that a negative interim PET-CT after two to four cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) is predictive of favorable outcome independent of IPS score. Currently, there are several ongoing trials that aim to determine whether early-response assessment can be used to select patients who might benefit from modifications of subsequent therapy, either by intensifying or abbreviating regimens and/or omitting radiotherapy with promising early results. Longer follow-up is required to assess whether this strategy impacts overall survival (OS). Herein, we review the results of recent trials using interim PET-CT-based adaptive design in the treatment of advanced HL.