Primary Refractory Hodgkin Lymphoma Research Articles

Outcome analysis of autologous stem cell transplantation in refractory and relapsed Hodgkin lymphoma: Insights from a North African single-institution study.

172 Background: The standard therapy for primary refractory or relapsed Hodgkin lymphoma (HL) involves the administration of high-dose chemotherapy followed by autologous stem cell transplantation (HDC/ASCT). Nevertheless, several risk factors may influence survival outcomes. We assessed outcomes of patients in this setting who underwent HDC/ASCT by performing survival analysis and studying prognostic factors affecting survival. Methods: We conducted a single-institution retrospective analysis of patients with relapsed/refractory HL who received HDC/ASCT between January 2018 and December 2022. Patients’ status evaluation before ASCT was performed by Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) Scan and Computed Tomography (CT) Scan. The used conditioning regimen was BEAM (Carmustine, Etoposide, Cytarabine, and Melphalan). The primary endpoints were progression-free survival (PFS) and overall survival (OS). Survival analysis was performed using the Kaplan-Meier method, and survival differences between groups were assessed using the Log-Rank test. Results: Thirty-five patients diagnosed with relapsed/refractory HL were included in the study. Among them, 26 patients (74%) had refractory disease, while 9 patients (26%) relapsed following completion of first-line chemotherapy. All patients were treated with HDC/ASCT. Prior to ASCT, 30 patients underwent assessment using FDG-PET Scan, while CT Scan was employed for evaluation in 5 patients. Twenty-three patients (66%) were in complete remission, 8 patients (23%) were in partial remission, and 4 patients (11%) had progressive disease. With a median follow-up of 24.36 months after transplantation, 28 patients (80%) were in remission, 6 patients (17%) had disease progression, and one patients died of septic shock. The 2-year PFS and OS rates for the total population were 85.4% and 97.1%, respectively. Response to first-line chemotherapy did not have a substantial impact on prognosis, as evidenced by a 2-year PFS rate of 76.2% vs. 88.9% (p=0.88) and a 2-year OS rate of 100% vs. 96.2% (p=0.56) for patients with relapsed and refractory disease, respectively. The 2-year PFS and OS rates for patients receiving autograft during complete remission, partial response, and tumor progression were 93.8% vs. 87.5% vs. 50% (p=0.005), respectively; and 95.7% vs. 100% vs. 100%, respectively (p=0.77). Patients who had negative pre-transplant PET-Scans demonstrated a 2-year PFS rate of 92.9% vs. 64.8% for those with positive PET-scans (p=0.004). Conclusions: The findings of our study affirm the established practice of HDC/ASCT for individuals facing relapsed/refractory HL. The disease status at transplant and the pre-transplant PET-Scan status prove to be crucial factors in predicting patients’ outcomes, while response to first-line chemotherapy did not influence prognosis.

Successful treatment of paediatric refractory Hodgkin lymphoma with immunotherapy - A case report and literature review.

To describe a rare case of primary refractory Hodgkin lymphoma nodular sclerosis syncytial variant in a child and review immunotherapy in relapsed/refractory Hodgkin lymphoma. We described the treatment course of a child with primary refractory classic Hodgkin lymphoma and discussed different options for salvage therapy, with an emphasis on immunotherapy. We searched PubMed for all published clinical trials investigating immunotherapy in classic Hodgkin lymphoma written in English until 31 June, 2023. The reference list of each identified paper was searched for additional publications. Our patient was salvaged with anti-programmed cell death 1 (PD-1) antibody therapy followed by high-dose chemotherapy with autologous stem cell rescue. Radiotherapy was avoided. We identified five one-armed phase II trials investigating anti-PD-1 therapy in first relapse/refractory disease in a total of 254 patients aged 9-71 years, of which one included 31 children. The complete remission rate before high-dose chemotherapy was 59%-95% overall and 67%-89% among those with refractory disease. Although it remains to be proven in randomised trials, anti-PD-1 therapy may provide higher complete response rates than traditional chemotherapy. Anti-PD-1 therapy has the potential to increase the chance of cure while decreasing the risk of late effects from chemotherapy and radiotherapy.

Prognostic model using 18F-FDG PET radiomics predicts progression-free survival in relapsed/refractory Hodgkin lymphoma

AbstractInvestigating prognostic factors in patients with relapsed or primary refractory classical Hodgkin lymphoma (R/R cHL) is essential to optimize risk-adapted treatment strategies. We built a prognostic model using baseline quantitative 18F-fluorodeoxyglucose positron emission tomography (PET) radiomics features and clinical characteristics to predict the progression-free survival (PFS) among patients with R/R cHL treated with salvage chemotherapy followed by autologous stem cell transplantation. Metabolic tumor volume and several novel radiomics dissemination features, representing interlesional differences in distance, volume, and standard uptake value, were extracted from the baseline PET. Machine learning using backward selection and logistic regression were applied to develop and train the model on a total of 113 patients from 2 clinical trials. The model was validated on an independent external cohort of 69 patients. In addition, we validated 4 different PET segmentation methods to calculate radiomics features. We identified a subset of patients at high risk for progression with significant inferior 3-year PFS outcomes of 38.1% vs 88.4% for patients in the low-risk group in the training cohort (P < .001) and 38.5% vs 75.0% in the validation cohort (P = .015), respectively. The overall survival was also significantly better in the low-risk group (P = .022 and P < .001). We provide a formula to calculate a risk score for individual patients based on the model. In conclusion, we developed a prognostic model for PFS combining radiomics and clinical features in a large cohort of patients with R/R cHL. This model calculates a PET-based risk profile and can be applied to develop risk-stratified treatment strategies for patients with R/R cHL. These trials were registered at www.clinicaltrials.gov as #NCT02280993, #NCT00255723, and #NCT01508312.

Impact of Risk Factors and Long Term Survival Analysis of Patients With Primary Refractory Hodgkin Lymphoma Who Underwent High Dose Chemotherapy and Autologous Stem Cell Transplant

Patients with primary refractory Hodgkin lymphoma (ref-HL) can still be salvaged with high dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT). Outcome of patients with ref-HL is poorer than those with relapsed HL, but most studies have included patients with both relapsed and refractory diseases, and separate analyses or studies on patients with ref-HL are limited. This study aimed to evaluate the outcomes of HDC auto-SCT and impact of various prognostic factors on patients with ref-HL both at the time of primary treatment failure and also on subsequent survival at the time of failure post HDC auto-SCT. This was a retrospective, single-institution, cohort analysis using HDC and auto-SCT database, approved by the Institutional Research Advisory Counsel and Ethics Committee for identifying patients. We used Fine and Gray competing risk analysis method, regression model for outcome analysis and Kaplan-Meier method (KM) for survival. Two hundred consecutive ref-HL patients underwent HDC auto-SCT between 1996 to 2019. Median age was 22.75 years, median follow-up 106 months. Post auto-SCT, disease status was complete remission (CR), partial remission, and progressive disease in 122 (61%), 22 (11%), and 47 (23.5%) patients, respectively. KM median progression-free survival (PFS) after auto-SCT was 43.9 months (5:10 years, 49.3%:45.5%). Median overall survival (OS) was 168.6 months (5:10 years, 61.2%:56.2%). Eighty-five patients (44.5%) died - 69 (34.5%) due to disease. For both PFS and OS, multivariate analysis identified similar adverse factors. For PFS, stage III-IV at relapse (HR=1.65, P=0.045), mediastinal involvement (HR=2.01, P=0.009), and no CR after salvage chemotherapy (HR=2.2, P=0.001) as adverse factors. PFS with 0-1 (not reached), 2 (40.8), 3 adverse factors (5.4 months) were significant (p<0.001). For OS, stage III-IV at relapse (HR=1.68, P=0.045), mediastinal involvement (HR=2.52, P=0.007), and no CR after salvage chemotherapy (HR=2.15, P=0.004) were significant. OS with 0-1 (not reached), 2 (148.5) 3 adverse factors (34.4 months) were significant (p<0.001). Median OS after auto-SCT failure was 23.6 months; patients received post auto-SCT brentuximab/second SCT (not reached), other treatments (22.5 months), and supportive care (8.4) (p<0.001). OS with five risk factors, present at HDC auto-SCT failure, (stage III-IV, failure <12 months, tumor >5 cm, B-symptoms, low albumin) showed that 0-1:2:3-5 risk factors had 152:30.9:9.45 months OS (p<0.001). Ref-HL patients have encouraging survival after HDC auto-SCT and can even be salvaged after auto-SCT failure. Based on prognostic factors, survival prediction is possible. Patients who fail to respond to HDC auto-SCT may benefit from newer treatments strategies and may qualify for enrollment in clinical trials.

Maintenance therapy with Everolimus in patients with refractory or relapsing Hodgkin lymphoma after autologous stem cell transplantation.

Patients with relapsing or primary refractory Hodgkin lymphoma, still have unsatisfactory outcomes after high dose chemotherapy followed by autologous stem cell transplantation (ASCT). Brentuximab Vedotin (BV) is the only approved agent for maintenance therapy for up to one year in these patients, however, this agent is often not available or affordable for many patients, especially in the developing countries. In this study, we used Everolimus as maintenance therapy after ASCT among patients with relapsing/refractory Hodgkin lymphoma. We collected the data of 20 patients with primary refractory or relapsing Hodgkin lymphoma who had undergone ASCT between June 2016 and June 2021. Everolimus was started at 10 mg daily on day +90 after ASCT for at least two years in patients with stable disease status, confirmed by imaging modalities. Patients were followed for disease status and drug side effects every 3 months. In our single-arm case-series study, the median duration of treatment was 22.95 months. Except for three patients, who had progression, others had no progression and are still receiving Everolimus (85%). No serious side effect was seen. We had no mortality due to disease recurrence. Until now, results showed promising effects of Everolimus in patients with relapsing or primary refractory Hodgkin lymphoma as maintenance therapy after ASCT.

Long Term Survival Analysis and Impact of Risk Factors Based Survival Model in Two Hundred Patients with Primary Refractory Hodgkin Lymphoma Who Underwent High Dose Chemotherapy and Autologous Stem Cell Transplant

Background: High dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT) can still salvage many patients with refractory Hodgkin lymphoma (HL). We are reporting patient's presentation, management and outcome of patients who underwent HDC auto-SCT at our institution and also analyzed the impact of various prognostic factors in these patients. We are reporting one of the largest single institution data and first report from the Middle Eastern countries analyzed to date. Design: From 1996-2019, 200 consecutive patients with refractory HL underwent HDC auto-SCT in Adult Medical Oncology are included using retrospective/prospective transplant data base. Fine and Gray competing risk analysis method and regression model for outcome analysis was used. Kaplan-Meir (KM) method was used to estimate 5-year progression free survival (PFS), defined as the time from diagnosis to disease relapse or progression or start of salvage due to primary treatment failure or death from any cause, whichever came first. Overall survival (OS) was defined as the time from diagnosis to death from any cause. Results: Male/female is 54.5%/45.5%, median age at auto-SCT is 22.75 years. Median follow-up is 106 months (12.5 - 271 months). Post HDC auto-SCT, disease status was complete remission (CR) 122 (61%), partial remission 22 (11%), no response 1 and progressive disease in 47 (23.5%) patients. Kaplan-Meir (KM) estimated median progression free survival (PFS) from HDC auto-SCT was 43.9 months (49.3% at 5 years, 45.5% at 10 years). Median overall survival (OS) was 168.6 months (61.2% at 5 years, 56.2% at 10 years). 115 (57.5%) patients are alive, 85 (44.5%) had died; 69 (34.5%) due to disease. Multivariate analysis identified three adverse risk-factors, similar for both PFS and OS. For PFS, stage III-IV at relapse (HR=1.65, P=0.045), mediastinal involvement (HR=2.01, , P=0.009) and no CR after salvage chemotherapy (HR=2.2, P=0.001) were significant. PFS for patients with 0-1 (not reached), vs 2 (40.8 months) vs 3 (5.4 months) risk-factors were significant (P=<0.000). For OS, stage III-IV at relapse (HR=1.68, P=0.045), mediastinal involvement (HR=2.52, P=0.007) and no CR after salvage chemotherapy (HR=2.15, P=0.004) were significant. OS with 0-1 (not reached), vs 2 (148.5 months) vs 3 (34.4 months) risk factors were highly significant (P=<0.000). Median OS after HDC auto-SCT failure was 23.6 months; for patients who received brentuximab or 2nd SCT (not reached): other treatment (22.5 months): supportive care only (8.4 months) was significant difference (P=<0.000). Using five-point risk factors based model (Figure E) for "post HDC auto-SCT failure outcome", (presence of stage III-IV, failure <12 months, tumor size >5 cm, B symptoms and low albumin) KM-OS in patients with 0-1 risk factor (152 months): 2 risk factors (30.9 months): 3-5 risk factors (9.45 months) was highly significant (P=<0.000). Conclusion: Refractory HL patients have encouraging survival after HDC auto-SCT and can even be salvaged after auto-SCT failure. Various prognostic factors at various time frames can predict outcome and may help in selecting patients for various emerging therapies. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

P113: Promising results with anti-PD-1 therapy in primary refractory Hodgkin lymphoma: a single-centre report

P113: Promising results with anti-PD-1 therapy in primary refractory Hodgkin lymphoma: a single-centre report

Own experience in the treatment of primary refractory Hodgkin's lymphoma. Case report

Despite significant progress made in recent decades in the treatment of classical Hodgkin's lymphoma, in 1030% of patients develop a refractory course or relapse of the disease. The effectiveness of therapy of the second and subsequent lines is about 50%. A significant breakthrough in the treatment of recurrent/refractory forms of classical Hodgkin's lymphoma has been the introduction of targeted drugs. The inclusion of new drugs in previously standard rescue therapy regimens significantly improves the effectiveness of the therapy. A clinical case of treating a patient with the progression of classical Hodgkin's lymphoma after first-line therapy, the use of brentuximab vedotin in combination with bendamustine as a rescue therapy with the achievement of complete remission, followed by high-dose consolidation with autologous hematopoietic stem cell transplantation is presented.

Neue Ansätze zur Behandlung des rezidivierten oder refraktären Hodgkin Lymphoms

BackgroundWhile classical Hodgkin lymphoma (HL) is curable in most cases with risk-adapted first-line therapy, the treatment of patients with relapsed or primary refractory (r/r) HL in particular remains a challenge.MethodsThis review article discusses the currently available data on the safety and efficacy of newer therapeutic approaches for r/r HL from a practice-oriented perspective.ResultsIn patients suitable for intensified therapy, durable remission can be achieved in approximately 50% of cases with polychemotherapy-based salvage followed by high-dose chemotherapy with autologous stem cell transplantation (ASCT). With the approval of targeted agents, even multiply relapsed, refractory, elderly, or multimorbid patients now have multiple treatment options. In addition to the anti-CD30 antibody–drug conjugate brentuximab vedotin (BV), the two anti-PD1 antibodies nivolumab and pembrolizumab are increasingly being used here as immune checkpoint inhibitors. The anti-PD1 antibodies are also used in earlier lines of therapy, e.g., significantly longer progression-free survival (PFS), was achieved with pembrolizumab in an international phase III trial compared to BV with comparable response rates. The therapeutic landscape of r/r HL is rapidly changing and additional promising targeted agents such as the antibody–drug conjugate camidanlumab tesirine, different checkpoint inhibitors, and anti-CD30 CAR T cells are currently being tested in trials.ConclusionsRational use of available therapeutic approaches is expected to improve the prognosis of patients with multiple r/r HL.

Combined prognostic role of TARC and interim 18F-FDG PET/CT in patients with Hodgkin lymphoma-real world observational study.

Although the majority of patients with Hodgkin lymphoma (HL) has recently become long-term survivors, 20%-30% of HL patients have primary refractory disease or relapse. It is essential to identify patients at risk of treatment failure during first-line therapy. To objective of the present study was to investigate the combined prognostic role of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) imaging and thymus and activation-regulated chemokine (TARC) levels in Hodgkin lymphoma. Between 01/01/2013 and 01/03/2019 77 HL patients were enrolled in this study where serum TARC levels were measured by an immunoassay and 18F-FDG PET/CT scans were performed at baseline, after the second cycle of ABVD treatment (interim) and at the end of first-line therapy. Twenty-six patients (34%) had early-stage HL, while 51 patients presented with advanced-stage disease. Fifteen patients had primary refractory HL, while 1 patient relapsed after first-line therapy. Optimal TARC cut-off value for progression-free survival (PFS) was 700pg/mL based on receiver operating characteristic (ROC) curve analysis. With Cox regression analysis, 18F-FDG PET/CT with Deauville scores of 3, 4, or 5 and TARC levels above 700pg/mL predicted treatment failure at interim assessment. Inclusion of HL patients with a Deauville score of 3 to the high-risk population resulted in a 7-fold increase in the estimated risk of relapse compared to patients with Deauville score 4-5 with TARC levels above 700pg/mL. Patients with interim 18F-FDG PET/CT Deauville scores 3-5 had a significant survival benefit if their TARC levels were 700pg/mL. Positive predictive value (PPV) of interim 18F-FDG PET/CT scans with a Deauville score 3-5 was 47.8%, while combined PPV of a similar 18F-FDGPET/CT assessment and elevated TARC levels was 88.8%. Interim 18F-FDG PET/CT and TARC analyzed together accurately identify HL patients who do not respond sufficiently to treatment and who need an early change of therapy.

A Phase II Single Arm Study of Nivolumab As Maintenance Therapy after Autologous Stem Cell Transplantation in Patients with Hodgkin Lymphoma at Risk of Relapse or Progression

Introduction: Autologous stem cell transplants (ASCT) are standard of care for patients with primary refractory or recurrent Hodgkin lymphoma (HL). While transplant results in cure for some patients, others relapse and succumb from their disease. Studies have found high expression of programmed death ligand 1 (PD-L1) in HL cells. The anti-PD-1 monoclonal antibody, nivolumab, has been safe and efficacious in the treatment of relapsed, refractory HL (Ansell et al. 2015). We evaluated the safety and efficacy of nivolumab maintenance therapy post-ASCT in high risk for relapse Hodgkin disease.Methods: Patients with HL with high risk of residual disease following ASCT ( high risk defined as refractory disease, relapse <12 months, or relapse ≥12 months with extranodal disease after frontline therapy) received nivolumab (240 mg IV every 2 weeks) starting 45-180 days post-transplant for a maximum of 6 months of treatment. Patients were followed for AEs through 100 days after the last dose of drug. PET-CT response assessments were performed 1-3 month, 6 month, and 12 month post-ASCT. The primary objective was to evaluate the safety and tolerability of nivolumab as maintenance therapy early after ASCT. The secondary objective was to evaluate progression-free survival (PFS) at 12 months post-transplant.Results: To date, 37 patients were enrolled; median age 36 years; 25 patients (68%) male. The median number of prior systemic regimens was 2 (range 2-4). 25 patients (68%) had relapsed disease, and 12 patients (32%) had primary refractory disease. 18 patients (49%) had extranodal disease at relapse, 6 patients (16%) had B-symptoms at relapse, and 11 patients (30%) had residual disease after salvage, including 10 patients (27%) of whom had 2-3 prior salvage therapies. 22 patients (60%) had received prior brentuximab, and 3 patients (8%) had received prior nivolumab or pembrolizumab. 36 patients received ASCT and 1 patient received tandem ASCT. At the time of data cutoff, 28 patients (76%) had discontinued nivolumab treatment, 22 patients (60%) because they had completed the 6-month treatment course, 4 patients (11%) due to an adverse event (AE) (1 patient each with pain, pneumonitis, rhabdomyolysis, or hypothyroidism), and 2 patients (5%) due to disease progression. The median duration of treatment was 22.1 weeks. 17 patients (46%) experienced a treatment-related AE (TRAE), of which 5 patients (14%) experienced a ≥Grade 3 TRAE. The most common (≥5%) TRAEs were diarrhea, fatigue, bone pain, neutrophil count decreased, pruritus, rash, and vomiting. 2 patients experienced a treatment-related serious AE (pneumonitis, rhabdomyolysis). There were no treatment-related deaths. With a median follow up of 9.2 months, the median PFS and overall survival (OS) have not been reached. The 6 month PFS is 92.1% and the 12-month OS is 100%. There were no differences in OS when stratified based on prior treatment.Conclusions: The use of nivolumab maintenance early after ASCT is safe and tolerable in this high risk patient population. Early efficacy data is promising, but data need to mature to determine the 12 month PFS. [Display omitted] DisclosuresBachier: CRISPR: Membership on an entity's Board of Directors or advisory committees; Autolus: Membership on an entity's Board of Directors or advisory committees; Nkarta: Membership on an entity's Board of Directors or advisory committees; Mana: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Shah: Umoja: Consultancy; Incyte: Consultancy; Legend: Consultancy; Kite: Consultancy; Miltenyi Biotec: Consultancy, Honoraria, Research Funding; Lily: Consultancy, Honoraria, Research Funding; Epizyme: Consultancy.

Effect of Brentuximab Vedotin Addition to Chemotherapy and Prognostic Factors in Patients with Relapsed/Refractory Hodgkin Lymphoma: A Large Multi-Trial Analysis Based on Individual Patient Data

Effect of Brentuximab Vedotin Addition to Chemotherapy and Prognostic Factors in Patients with Relapsed/Refractory Hodgkin Lymphoma: A Large Multi-Trial Analysis Based on Individual Patient Data

Dose-dense brentuximab vedotin plus ifosfamide, carboplatin, and etoposide for second-line treatment of relapsed or refractory classical Hodgkin lymphoma: a single centre, phase 1/2 study

Relapsed or refractory classical Hodgkin lymphoma could be treated with multiagent salvage chemotherapy followed by autologous haematopoietic stem-cell transplantation. The aim of this study is to establish the safety and activity of dose-dense brentuximab vedotin combined with ifosfamide, carboplatin, and etoposide (BV-ICE) chemotherapy in second-line treatment of classical Hodgkin lymphoma. We conducted a single-arm, open-label, phase 1/2 study of dose-dense BV-ICE at the Seattle Cancer Care Alliance, University of Washington (Seattle, WA, USA). Eligibility criteria were age 18 years or older; diagnosis of first relapse, primary refractory classical Hodgkin lymphoma after one previous line of therapy; measurable disease of at least 1 cm in the longest axis, CT of chest, abdomen, and pelvis with PET within the past 28 days; Eastern Cooperative Oncology Group performance status of 0-1; and adequate organ function. A 3 + 3 dose escalation study was done for the phase 1 part of the trial to establish the maximum tolerated dose to be used for the phase 2 study. Brentuximab vedotin was delivered on days 1 and 8 at either 1·2 mg/kg (dose level 1) or 1·5 mg/kg (dose level 2) intravenously (capped at 150 mg) with standard dosing of ICE on days 1-3 (ifosfamide 5 g/m2 plus mesna 5 g/m2 intravenously over 24 h on day 2, carboplatin area under the curve 5 on day 2 in one intravenous injection, and etoposide 100 mg/m2 on days 1-3 in one intravenous injection per day) for two 21-day cycles. The primary endpoint was to establish the recommended phase 2 dose (phase 1 part) and complete response rate after two cycles, with a prespecified target of 78% (phase 2 part). Safety analysis was done in all enrolled participants and the primary activity analysis was done in all patients with evaluable response data. This study is registered with ClinicalTrials.gov (NCT02227199); enrolment and study treatment are complete. Between Oct 16, 2014, and Feb 10, 2020, we enrolled 45 patients with a median age of 31 years (IQR 28-45). The recommended phase 2 dose of brentuximab vedotin was established to be 1·5 mg/kg. After a median follow-up of 3·1 years (IQR 1·7-4·1), 32 (74%; 95% CI 58·8-86·5) of 43 evaluable patients had complete responses after two cycles of treatment. Grade 3-4 haematological toxic effects were common, including neutropenia (33 [73%]), anaemia (six [13%]), and thrombocytopenia (36 [80%]). The most common grade 3-4 non-haematological toxic effects were febrile neutropenia (four [9%]), sepsis (six [13%]), increased alanine aminotransferase (five [11%]), hyperglycaemia (three [7%]), pulmonary embolism (two [4%]), and increased aspartate aminotransferase (two [4%]). There was one (2%) on-treatment death due to multisystem organ failure that was considered treatment related. Serious adverse events occurred in 13 (29%) patients. Our data suggest that dose-dense BV-ICE is a rapidly administered and active salvage regimen for patients with relapsed or refractory classical Hodgkin lymphoma despite a complete response in this trial lower than the prespecified phase 2 target. Although cross-trial comparisons should be made with caution, activity results seem to be similar to previously presented brentuximab vedotin chemotherapy salvage combinations delivered over much longer durations and can be considered in young (<60 years), transplantation-eligible patients for second-line therapy. Seagen, Lymphoma Research Foundation, National Institutes of Health/National Cancer Institute, and generous philanthropic donations to the University of Washington from numerous individuals and families in support of lymphoma research.

The Bbv Regimen: A Phase II Study with Bendamustine Plus Brentuximab Vedotin in Hodgkin Lymphoma and CD30+ Peripheral T-Cell Lymphoma in First Salvage Setting

Lymphoma patients with primary refractory disease, particularly prior to autologous stem cell transplant (ASCT) requires novel salvage options inducing high complete response (CR) rates.Brentuximab vedotin (BV) and bendamustine (B) both showed activity in relapsed Hodgkin lymphoma (HL) patients as monotherapy. Their combination (BBV regimen) in heavily pretreated patients with multiply relapsed or refractory HL and anaplastic large cell lymphoma resulted in an overall response rate (ORR) and CR rate of 67% and 19%, respectively. In a second study in which BV+B was used in HL patients with primary refractory disease or at first relapse reported ORR and CR rate of 93% and 73%, respectively.This is a single-arm, open-label, multicenter, phase II clinical trial on the efficacy and safety of the BBV regimen as first salvage therapy in patients with relapsed or refractory HL or peripheral T-cell lymphoma (PTCL).A total of 25 patients with PTCL, and 40 with HL are expected to be enrolled. In the study, intravenous B will be administered at a dose of 90 mg/m2 on day 1 and 2 and BV will be given intravenously at a total dose of 1.8 mg/kg on day 1 of each 21 days-based cycle, for 6 cycles. All patients achieving a CR can be considered eligible to peripheral blood stem cell mobilization and may proceed to an ASCT at any time after cycle 4. A first protocol amendment introduced and age upper limit (patients must be 18-60 years old) due to safety concerns of the combination in elderly people.The HL cohort has been is closed while the PTCL cohort is still open (only 3/25 patients were enrolled). The steering committee decided to amend the study protocol to include any relapse/refractory PTCL patients (any line of treatment instead of patients with primary relapsed/refractory disease).Forty HL patients had restaging, of whom 31 had a response leading to an ORR of 77.5%. 28 patients had already the first restaging after ASCT: 23 are still in CR while 5 had relapse. Due to sever skin toxicity (grade ≥3) 6 patients stopped the regimen after second cycle. Being anyway in CR, these patients underwent ASCT consolidating their response. No grade 4 adverse events (AEs) were report, but we point out skin rashes (25%) related to study drugs combination.Albeit early, these data suggest that the BBV regimen exhibits promising results in a challenging sub-population of HL patients. Emerging data could continue to establish that BBV is an effective approach that could represent a new bridge to ASCT in primary refractory HL and a valid salvage option for relapsed/refractory PTCL. Long term follow up will clarify if the BBV regimen induces either a long disease control. DisclosuresCorradini:Amgen: Honoraria; Celgene: Honoraria; Novartis: Honoraria; Gilead: Honoraria; Janssen: Honoraria; Roche: Honoraria; Takeda: Honoraria; Sanofi: Honoraria. Zinzani:Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Changes in Serum TARC Predict PET Response Among Pediatric Patients with Relapsed or Refractory Hodgkin Lymphoma Treated with Brentuximab Vedotin and Gemcitabine: A Report from the Children's Oncology Group

Patients with primary refractory Hodgkin lymphoma (HL) or who relapse less than one year after completion of initial therapy will frequently respond to second line therapy. A majority of those who have a complete response (CR) to salvage therapy, and are then consolidated with high-dose chemotherapy and autologous stem cell rescue will experience prolonged relapse-free survival. It is therefore critical to identify those patients who are unlikely to respond to a given salvage regimen, so they can be given alternate treatment.Serum thymus and activation related chemokine (TARC) is expressed by Hodgkin Reed Sternberg cells, roughly reflects tumor bulk, and decreases with treatment response among adults with HL (Plattel W, Van Den Berg A, et al., ASH, 2010). We hypothesized that the degree of reduction of serum TARC after salvage therapy would distinguish those patients with relapsed/refractory HL who go on to have a CR from those with less than a CR.Children's Oncology Group (COG) protocol AHOD1221 was the first clinical trial to combine the antibody-drug conjugate, brentuximab vedotin (Bv), with conventional chemotherapy (gemcitabine) for children and young adults with HL. The majority (35 of 42 treated at the recommended phase 2 dose level; 83%) had primary refractory disease or very early relapse <6 months after completion of primary treatment. 27 of 40 evaluable patients experienced a CR (68%) within the first four cycles, defined by all target lesions Deauville 3 or less on FDG-PET scan (Cole et al., ASCO, 2017). 87% of CRs were observed after two cycles of therapy.Serum was collected at the start of every cycle, and serum TARC was measured using singleplex ELISA. At baseline, 37 of 38 patients (97%) had elevated serum TARC (median 5700 pg/mL; range 379-18,667). Median serum TARC decreased to 668 pg/mL (range 6-9718; n=35; P<0.0001) after one cycle of therapy, and 368 pg/mL (range 47-1749; n=22; P<0.0001) after two cycles. 31 of 40 evaluable patients (78%) had paired serum samples collected at baseline and after one cycle of therapy. Patients who had a CR within the first four cycles of therapy showed a greater reduction in serum TARC after one cycle of therapy (median reduction from baseline = 86%; n=15) than those who did not have a CR (median 61%; n=16; P=0.03, Mann Whitney test). Six of 15 patients who had a CR showed more than a 90% reduction in serum TARC after one cycle of therapy, compared with 1 of 16 patients who did not have a CR (P=0.04, Fisher's exact test). At later time points, neither absolute serum TARC values nor reduction from baseline differed significantly between those patients with a CR and remaining subjects.In summary, serum TARC decreases significantly from baseline after one cycle of treatment with Bv and gemcitabine among children and young adults with relapsed or primary refractory HL. Patients with a CR demonstrated a more rapid reduction in serum TARC from baseline than those who did not have a CR. This is the first report demonstrating the usefulness of TARC as a biomarker of treatment response specifically among children and young adults with HL. Future studies will test the value of altering retrieval strategy based on this early response marker. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

A Cure Rate Survival Model after Stem Cell Transplantation for Relapsed or Refractory Hodgkin Lymphoma Patients

Background: Hodgkin lymphoma (HL) is one of the best curable malignancies. Randomized controlled studies have validated the benefit of hematopoietic stem cell transplant (HSCT) for patients with relapsed or primary refractory HL. This analysis aimed to identify significant prognostic factors on the recurrence of the disease after HSCT applying a cure rate model. Method: In this retrospective cohort study, there were 92 patients with HL who underwent HSCT from 2007 to 2014 with 18 months of follow-up in Tehran, Iran. The survival time was set as the time interval between transplantation and the recurrence of HL. In addition, we utilized hyper-Poisson distribution as discrete frailty to account the unobserved heterogeneity and random effects. Results: In noncured cases, the mean of survival time was 318 (95% confidence interval, 144-493) days. The 1-, 3- and 5-year survival rates were 88.9%, 83.4%, and 80.7%, respectively. A significant association was observed between the cured patients and the variables such as age, the experience of pre-transplantation relapse, hemoglobin (Hb), mononuclear cells (MNCs), and body surface area (BSA) at the time of transplantation. Conclusion: The study concluded that less than 30 years of age, a high level of Hb (g/dl), a low level of MNCs and BSA (m2), and the absence of pre-transplantation experience of relapse were associated with better survival following HSCT. Based on this study, post-transplant consolidation therapies could be considered for the treatment of HL patients after HSCT.

Consolidation with Nivolumab and Brentuximab Vedotin after Autologous Hematopoietic Cell Transplantation in Patients with High-Risk Hodgkin Lymphoma

Consolidation with Nivolumab and Brentuximab Vedotin after Autologous Hematopoietic Cell Transplantation in Patients with High-Risk Hodgkin Lymphoma

Characteristics and outcome of patients with relapsed/refractory Hodgkin lymphoma following front-line escalated BEACOPP-based chemotherapy: a report from the Australasian Lymphoma Alliance

The optimal management of the small number of patients who experience early failure of eBEACOPP in Hodgkin lymphoma (HL) is unclear. We identified 12 patients with HL who progressed within 12 months of the front-line therapy between January 2010 and July 2019. Median time of first progression following diagnosis was 7 months (range 2.1–13.2). Nine patients proceeded to stem cell therapy following salvage therapy (8 autografts, 1 allograft). Seven patients received novel therapy after relapse, of these, 6 were alive at census, versus 2 out of 5 of those who had standard therapy alone. At the end of follow up (median 22 months), 4 were deceased from progressive disease, 6 were in complete remission and 2 in partial remission on continuing therapy. The outcome of patients with primary refractory HL to eBEACOPP therapy is better than expected and the use of a novel agents after relapse may be a contributing factor.

Real-world efficacy of brentuximab vedotin plus bendamustine as a bridge to autologous hematopoietic stem cell transplantation in primary refractory or relapsed classical Hodgkin lymphoma

Up to 30% of patients with classical Hodgkin lymphoma (cHL) are not responsive to frontline therapy or relapse after primary treatment. In these cases, autologous hematopoietic stem cell transplantation (AHSCT) is the standard of care. The combination of brentuximab vedotin and bendamustine (BV + B) is an effective salvage regimen in this challenging subpopulation. This nationwide multicenter study investigated the real-world efficacy and safety of the BV + B regimen as a bridge to AHSCT in patients with primary refractory or relapsed cHL. A total of 41 cHL patients underwent AHSCT after receiving at least 1 cycle of BV + B (with brentuximab vedotin given at 1.8 mg/kg on day 1 and bendamustine at 90 mg/m2 on days 1–2 every 4 weeks). After a median of 3 (1–6) cycles of BV + B, the objective response rate was 78%, with 29 (70.7%) patients achieving complete remission. Twelve (29.3%) patients relapsed after AHSCT, 2 (4.9%) of them died, while 2 (4.9%) patients are lost to follow-up. After a median of 17 months of follow-up, the estimated 2-year overall- and progression-free survival after AHSCT was 93 and 62%, respectively. Features of advanced disease at recurrence (p = 0.038) and the presence of stage IV cHL at relapse (p = 0.024) are strong predictor markers of unfavorable outcomes. Twenty-four (58.5%) patients experienced adverse events of any grade, while no grade IV toxicities were reported. BV + B is an effective salvage option with a manageable toxicity profile in cHL. The real-world safety and efficacy of this combination are similar to the observations made on the study population.

The effect of gemcitabine, dexamethasone, and cisplatin chemotherapy in relapsed/refractory NHL and HL patients: A single center experience.

The optimal choice of salvage therapy for patients with relapsed/refractory non-Hodgkin lymphoma or Hodgkin lymphoma remains controversial. In this study, we aimed to share our experience in relapsed/refractory lymphoma patients who received GDP/R-GDP as salvage chemotherapy in our center. Data of 47 relapsed/refractory Hodgkin lymphoma and non-Hodgkin lymphoma patients who received GDP or R-GDP as salvage chemotherapy in our center between July 2014 and October 2017 were retrospectively evaluated. Non-Hodgkin lymphoma and Hodgkin lymphoma patients were divided into two groups as primary refractory and relapsed. The one-year overall survival was 100% (for relapsed) and 36.9% (for refractory) in the non-Hodgkin lymphoma groups, and 82.5% (for relapsed) and 80% (for refractory) in the Hodgkin lymphoma group. The one-year progression-free survival (PFS) was 72.7% (for relapsed) and 38.5% (for refractory) in patients with NHL, and 41% (for relapsed) and 18.2% (for refractory) in patients with HL. GDP/R-GDP seems to be a well-tolerated out-patient salvage regimen for relapsed/refractory non-Hodgkin lymphoma and Hodgkin lymphoma. Although proven efficacy, negative toxicity profile, and ease of administration, the application of gemcitabine-based therapy for patients with primary refractory non-Hodgkin lymphoma and Hodgkin lymphoma provided limited success.