Therapy In Advanced Hodgkin Lymphoma Research Articles

Long Follow-up of the Response-Adjusted Therapy for Advanced Hodgkin Lymphoma (RATHL) Trial (CRUK/07/033) Confirms the Safety of Both De-Escalation and Intensification of Chemotherapy

Long Follow-up of the Response-Adjusted Therapy for Advanced Hodgkin Lymphoma (RATHL) Trial (CRUK/07/033) Confirms the Safety of Both De-Escalation and Intensification of Chemotherapy

Advanced Hodgkin lymphoma in the East of England: a 10-year comparative analysis of outcomes for real-world patients treated with ABVD or escalated-BEACOPP, aged less than 60 years, compared with 5-year extended follow-up from the RATHL trial

Treatment with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) or escalated(e)-BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone) remains the international standard of care for advanced-stage classical Hodgkin lymphoma (HL). We performed a retrospective, multicentre analysis of 221 non-trial (“real-world”) patients, aged 16–59 years, diagnosed with advanced-stage HL in the Anglia Cancer Network between 2004 and 2014, treated with ABVD or eBEACOPP, and compared outcomes with 1088 patients in the Response-Adjusted Therapy for Advanced Hodgkin Lymphoma (RATHL) trial, aged 18–59 years, with median follow-up of 87.0 and 69.5 months, respectively. Real-world ABVD patients (n=177) had highly similar 5-year progression-free survival (PFS) and overall survival (OS) compared with RATHL (PFS 79.2% vs 81.4%; OS 92.9% vs 95.2%), despite interim positron-emission tomography-computed tomography (PET/CT)-guided dose-escalation being predominantly restricted to trial patients. Real-world eBEACOPP patients (n=44) had superior PFS (95.5%) compared with real-world ABVD (HR 0.20, p=0.027) and RATHL (HR 0.21, p=0.015), and superior OS for higher-risk (international prognostic score ≥3 [IPS 3+]) patients compared with real-world IPS 3+ ABVD (100% vs 84.5%, p=0.045), but not IPS 3+ RATHL patients. Our data support a PFS, but not OS, advantage for patients with advanced-stage HL treated with eBEACOPP compared with ABVD and suggest higher-risk patients may benefit disproportionately from more intensive therapy. However, increased access to effective salvage therapies might minimise any OS benefit from reduced relapse rates after frontline therapy.

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.

PET-adapted approaches to primary therapy for advanced Hodgkin lymphoma.

Recent results of randomized phase III studies of FDG-PET-adapted therapy for advanced Hodgkin lymphoma (HL) have clearly demonstrated benefit to alteration of treatment according to interim response, in particular regarding reducing toxicity while maintaining efficacy. However, these studies have differences in design including initial chemotherapy regimen, PET response criteria, patient populations enrolled, and inclusion of radiation, and report different results regarding efficacy and toxicities, which makes cross-trial comparisons difficult. Practitioners are presented with deciding which of these approaches will provide the optimum outcome, balancing toxicity and efficacy, and for which patient with advanced-stage HL. This review summarizes the observations reported from these trials and provides context to help guide physicians and patients in treatment decisions for advanced HL.

Optimisation of adaptive therapy for advanced Hodgkin lymphoma.

Optimisation of adaptive therapy for advanced Hodgkin lymphoma.

Potential Impact of Consolidation Radiation Therapy for Advanced Hodgkin Lymphoma: A Secondary Modeling of SWOG S0816 with Receiver Operating Characteristic Analysis

Potential Impact of Consolidation Radiation Therapy for Advanced Hodgkin Lymphoma: A Secondary Modeling of SWOG S0816 with Receiver Operating Characteristic Analysis

PET-adapted therapy for advanced Hodgkin lymphoma – systematic review

Introduction: Positron emission tomography-computed tomography (PET-CT) performed after two chemotherapy cycles (PET-2) has become an accepted prognostic tool in Hodgkin lymphoma (HL). We evaluated the effect of PET-adapted strategy on outcome in advanced stage HL.Methods: In August 2017, we searched electronic databases, conference proceedings and ongoing trials. We included all studies in which treatment modification for advanced HL was performed based on the results of the interim PET scan. The primary analysis included randomized controlled trials (RCTs). Outcomes were progression-free survival (PFS) and overall survival (OS).Results: We identified 13 studies (4 RCTs, 7 phase II and 2 retrospective studies), conducted between 1999 and 2014, including 6856 patients. Of the four RCTS: one used therapy escalation, one did de-escalation and two trials performed both. Outcomes were assessed at different time point between 2 and 5 years. Three RCTs for de-escalating therapy, obtained similar outcomes despite reducing therapy, with a 2-year PFS of 88–92% (6 escalated BEACOPP (EB) vs. 4 ABVD cycles), a 5-year PFS of 91–92% (6/8 EB vs. 4 EB cycles) and a 5-year PFS of 80–82% (6 ABVD vs. omitting bleomycin after two successful ABVD cycles). Two RCTs implemented escalation. The randomization was between adding rituximab or not. In both trials, it did not affect outcome, with a 4-year PFS of 68–69% (addition of rituximab to BEACOPP after 2 ABVD cycles) and 5-year PFS of 88–90% (addition of rituximab to EB after 2 EB cycles). Performing true randomization between PET-adapted and a standard ABVD control arm was not feasible, given historical data.Conclusions: This systematic review of PET-adapted therapy, mainly based on RCTs, suggests that a change to the treatment paradigm is appropriate in advanced HL.

PET-CT Adapted Therapy for Advanced Hodgkin Lymphoma: A Systematic Review of the Literature

PET-CT Adapted Therapy for Advanced Hodgkin Lymphoma: A Systematic Review of the Literature

PET-CT for staging and early response: results from the Response-Adapted Therapy in Advanced Hodgkin Lymphoma study

AbstractInternational guidelines recommend that positron emission tomography-computed tomography (PET-CT) should replace CT in Hodgkin lymphoma (HL). The aims of this study were to compare PET-CT with CT for staging and measure agreement between expert and local readers, using a 5-point scale (Deauville criteria), to adapt treatment in a clinical trial: Response-Adapted Therapy in Advanced Hodgkin Lymphoma (RATHL). Patients were staged using clinical assessment, CT, and bone marrow biopsy (RATHL stage). PET-CT was performed at baseline (PET0) and after 2 chemotherapy cycles (PET2) in a response-adapted design. PET-CT was reported centrally by experts at 5 national core laboratories. Local readers optionally scored PET2 scans. The RATHL and PET-CT stages were compared. Agreement among experts and between expert and local readers was measured. RATHL and PET0 stage were concordant in 938 (80%) patients. PET-CT upstaged 159 (14%) and downstaged 74 (6%) patients. Upstaging by extranodal disease in bone marrow (92), lung (11), or multiple sites (12) on PET-CT accounted for most discrepancies. Follow-up of discrepant findings confirmed the PET characterization of lesions in the vast majority. Five patients were upstaged by marrow biopsy and 7 by contrast-enhanced CT in the bowel and/or liver or spleen. PET2 agreement among experts (140 scans) with a κ (95% confidence interval) of 0.84 (0.76-0.91) was very good and between experts and local readers (300 scans) at 0.77 (0.68-0.86) was good. These results confirm PET-CT as the modern standard for staging HL and that response assessment using Deauville criteria is robust, enabling translation of RATHL results into clinical practice.

Patterns of Care and Survival Outcomes Examining Radiation Therapy for Advanced Hodgkin Lymphoma

The use of radiation therapy (RT) in advanced Hodgkin lymphoma (HL) is controversial, and currently optional, according to the National Comprehensive Cancer Network guidelines. The purpose of this analysis was to determine patterns of care in the United States and whether RT was associated with improved survival. Data from 1988–2011 was obtained from the Surveillance, Epidemiology, and End Results (SEER) cancer registry and used to determine patient characteristics and survival in adults (age ≥18 years) with stage III–IV HL who survived a minimum of 6 months. The survival minimum was used to minimize bias related to the delivery of RT after chemotherapy. The Kaplan-Meier method was used to determine overall survival (OS). Univariate and multivariate models (UVA, MVA) were analyzed using the log-rank test and Cox proportional hazards model, respectively. A sensitivity analysis was performed for patients diagnosed after 2000 to examine patients treated in a modern treatment era. Due to potential unmeasured confounders in the cohort who did not receive RT, a separate propensity-matched cohort of patients who did and did not undergo RT was created. A total of 9,467 adults (60% male) with advanced HL were included in the analysis. Median age was 39 years, 55% had stage III disease, and 19% of patients received RT. Median follow-up was 66 months for the entire cohort and 81 months for those alive at last follow-up. Stage III patients were more likely to get RT than stage IV patients, 22% versus 16% (P < .0001). Five-year OS for stage III patients for the no RT versus RT cohorts were 79% versus 88% (P < .0001). Five-year OS for stage IV patients for the no RT versus RT cohorts were 73% versus 84% (P < .0001). On MVA the following were associated with OS (all P < .005): RT (hazard ratio, HR = 0.85), older age as a continuous variable (HR = 1.04), Black race (HR = 1.32), female sex (HR = 0.75), stage IV (HR = 1.25), histology (HR = 1.0–1.4), and later year of diagnosis (HR = 0.97). A sensitivity analysis of patients diagnosed after 2000 revealed RT was associated with a HR = of 0.79 (P = .009) on MVA. Multivariate analysis by stage revealed that RT was not associated with survival in stage III patients, HR = 0.94 (P = .4), but was significant for stage IV patients, HR = 0.78 (P = .004). The propensity-matched cohort of patients resulted in 3 390 patients, of whom half received RT, and who were otherwise balanced among the risk factors analyzed. In this group, the hazard ratio for RT on univariate Cox regression was 0.75, (P < .0001). The results of this large study demonstrate a significant decline in utilization of RT from 1988 to 2011; additionally, the use of RT in advanced stage HL was associated with a survival benefit that was significant after multiple sensitivity analyses, particularly in patients with stage IV disease.

The choice of first-line therapy in advanced Hodgkin lymphoma: Retrospective comparison of ABVD and escalated BEACOPP regimen

8063 Background: HD patients with high risk have a relatively poor prognosis with less than 50% 5-year overall survival (OS) if treated with ABVD regimen. Methods: Therapy results of all 105 patients with advanced HL (CS IIBX -IV) treated from diagnosis at our Department in the last decade, are presented. The choice of initial 3 cycles between ABVD and escalated BEACOPP was done at the patients preferal and physician's adivice. Further 3 chemotherapy cycles depended on initial response assessment: poorly responding ABVD treated patients were offered therapy escalation. Patients with a good response (over 80% regression) after the first 3 cycles were later treated with ABVD. EFS and OS were primary endpoints of the study. Results: We divided patients into 2 treatment groups, depending on the first 3 cycles (escalated BEACOPP n = 57 or ABVD n = 48). Poor response resulting in therapy intensification was not considered as an event defined only as a relapse or progression during therapy. There was a statistically insignificant imbalance between the risk factor distribution with less favorable prognosis in patients treated with esc BEACOPP: 38 % of pts in IV th clinical stage (as compared to 31% in ABVD group), 3,08 EORTC risk factors (as compared to 2,64 in ABVD group) and 2,19 according to German Hodgkin Study Group (1.93 respectively). Increased toxicity of esc BEACOPP regimen was due to grade 3/4 cytopaenia (present in all patients) resulting in more infection episodes (according to WHO scale stage 3 - 16 pts , stage 4 - 8 pts; in ABVD group, 2 and 1 pt respectively). There were no treatment related mortalities. In esc BEACOPP projected 5 y OS was 96% and EFS 89% , which is comparable to GHSG results. 5 y OS and EFS in ABVD group are 87% and 66% respectively. The difference in EFS is statistically significant (p&lt; 0.05). Conclusions: In our study we checked the feasibility of esc BEACOPP regimen in high risk HD pts. The results show the importance of the intensity of the first line approach. In the poor responders after the initial 3 cycles, even early treatment intensification, didn’t improve the outcome. De-escalation of therapy after the first 3 cycles, in good responders, didn’t make OS and EFS inferior to GHSG results in which they recommend 6 cycles of esc BEACOPP therapy. No significant financial relationships to disclose.