scholarly journals 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

2021 ◽  
Vol 100 (4) ◽  
pp. 1049-1058 ◽  
Author(s):  
James Russell ◽  
Angela Collins ◽  
Alexis Fowler ◽  
Mamatha Karanth ◽  
Chandan Saha ◽  
...  

AbstractTreatment 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.

Hematology ◽  
2011 ◽  
Vol 2011 (1) ◽  
pp. 310-316 ◽  
Author(s):  
Ranjana Advani

AbstractAdvanced-stage Hodgkin lymphoma (HL) has become a curable disease in the majority of patients. Research during the last decade has challenged chemotherapy with Adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) as the standard of care and debates continue regarding the role of radiation therapy (RT) in this patient population. The incorporation of interim positron emission tomography (PET) imaging and, recently, further characterization of HL on cellular and molecular levels are emerging as tools for treatment stratification and predictors of disease status. Newer targeted therapies have emerged that are very effective in the relapsed setting and are actively being explored as frontline therapy. Lastly, the expanding population of survivors cured of HL outnumbers patients with the disease and needs to be monitored for therapy-related late effects.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 212-212 ◽  
Author(s):  
Volker Diehl ◽  
Carsten Kobe ◽  
Heinz Haverkamp ◽  
Markus Dietlein ◽  
Andreas Engert

Abstract Introduction The prospectively randomized HD15 multicenter trial of the German Hodgkin Study Group (GHSG) included advanced-stage Hodgkin lymphoma patients comparing 8 cycles of BEACOPPescalated with 6 cycles or 8 cycles time-condensed BEACOPPbaseline. One other main study endpoint was the prognostic value of 18F-fluorodesoxyglucose (FDG) positron emission tomography (PET) following chemotherapy. The aim was to specify the negative predictive value of PET (NPV) in patients with residual tumour mass after chemotherapy. Methods Entry criteria for the PET question were partial remission (PR) after the end of chemotherapy with at least one involved nodal site measuring more than 2.5 cm in diameter by computed tomography (CT). Exclusion criteria included diabetes, elevated blood sugar levels and skeletal involvement with risk of instability. Calculations were restricted to those cases with either progressive disease (PD) or relapse within 12 months after PET or at least 12 months of follow-up. A total of 275 patients were eligible for this analysis. The assessment was based on those patients confirmed by an expert panel as being PET-negative. CT verification was performed to identify false positive PET findings. The NPV was defined as the proportion of patients without progression or relapse within 12 months. Results 9/216 patients with PET-negative residues and 9/59 patients with PET-positive residues had PD or relapse within one year of follow-up. The NPV was 0.958% (95% CI 0.931 – 0.985%). In 244/245 cases with PET-negative residual masses, no irradiation was given. In the 62/66 cases with PET-positive residues, additional radiotherapy was performed. Progression/relapse rates were significantly different between those patients with residual mass being PET-negative or PET-positive (p=0.0053). PET-negative patients, who were assessed as partial response by CT, had a prognosis similar to those in complete remission. There was no significant difference in the progression free survival in this trial and the prior GHSG trials HD12 (arms pooled) and HD9 (arm C) for advanced-stage HL (p=0.266). Importantly, the proportion of patients receiving radiotherapy decreased from 70% (HD9-C) to 39% (HD12) and 12% (HD15). Discussion The high NPV of PET suggests that radiotherapy following 6 or 8 cycles of BEACOPP might be restricted to those patients who are PET-positive after chemotherapy.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4828-4828
Author(s):  
Lauren S. Maeda ◽  
Richard T. Hoppe ◽  
Saul A. Rosenberg ◽  
Sandra J. Horning ◽  
Ranjana H. Advani

Abstract Abstract 4828 Purpose: Stanford V is an abbreviated combined modality approach for the treatment of advanced stage Hodgkin lymphoma (HL). This regimen was developed with the aim of shortening the duration of chemotherapy, limiting the radiotherapy (RT) to a modified involved field and thereby potentially reducing short and long term toxicity while maintaining or improving cure rates. Specifically the chemotherapy regimen has significantly lower cumulative doses of adriamycin, bleomycin and alkylating agents compared to other standard regimens such as ABVD or escalated BEACOPP. We have previously reported excellent outcomes with this regimen with a freedom from progression (FFP) of 89% and overall survival (OS) of 96% (Horning, S.J., et al., J Clin Oncol 2002, 20:630-7). The purpose of this study was to determine the outcome of patients (pts) treated with secondary therapy after failing Stanford V. Methods: Pts with advanced stage HL who had either refractory disease or had relapsed after primary therapy with Stanford V, were retrospectively identified from the HL database. We analyzed this group of patients for risk factors, salvage therapy, and treatment outcome. Results: Between May 1989 and March 2003, 167 pts were treated on protocol. At a median follow-up of 12.8 years the outcomes are excellent with a 10-year FFP and OS of 87% and 93%, respectively. Therapy failed in 19 pts (11%) of which 16 relapsed and 3 did not complete the intended treatment (disease progression n=2, and muscle pain and hyponatremia n=1). The median age of pts who failed therapy was 31 years (range 21 – 58) with a median time to progression of 5.1 months (range 0.2 – 41.4). 11 pts relapsed at 0 to 12 months from completion of therapy and 8 pts relapsed at > 12 months. At initial diagnosis 5 had stage I/II disease with bulky mediastinum, 5 stage III and 9 stage IV disease. The International Prognostic Score (IPS) at initial diagnosis was 0–1 (n=4), 2–3 (n=10) and 4–7 (n=5). 13/19 (68%) pts relapsed outside the RT field, 2 infield, 3 both infield and outside and 1 unknown. 7/19 pts in whom therapy failed had bulky disease and of these 5 failed outside the RT field. Relapse was detected clinically in 12 pts, and on surveillance positron emission tomography scan performed every 3 to 6 months in 5 pts who were asymptomatic (2 pts unknown). 14/19 (74%) pts received secondary therapy with a platinum-containing regimen (ICE or DHAP) with an overall response rate (ORR) of 91% (complete response [CR] n=1, partial response [PR] n=9, progressive disease [PD] n=1, unknown response n=3), followed by an autologous hematopoietic stem cell transplant. 5 pts were treated with non-transplant regimens consisting of chemotherapy with MOPP/ABV + RT (n=2), ChlVPP (n=1), oral cyclophosphamide (n=1) and procarbazine/alkeran/adriamycin/etoposide (n=1), with an ORR of 80% (CR n=4). Reasons for non-transplant therapy were neuropathy (n=1), pt preference (n=1), liver disease (n=1), and unknown (n=2). 11 of the 19 pts in whom Stanford V failed died (disease progression n=3, second malignancy n=2, graft failure n=1, infection n=1, liver failure n=1, cardiac arrest n=1, suicide n=1 and unknown n=1). At a median follow-up of 8 years, the disease-specific survival (DSS), FFP and OS for pts with refractory or relapsed disease after Stanford V was 84%, 63% and 42%, respectively. Outcome of pts who relapsed within a year was worse than pts who relapsed > 1 year with an OS of 36% versus 50%, respectively. There was no difference in FFP for these groups, 64% versus 63%, respectively. Conclusions: The outcome of pts with advanced HL is excellent with the Stanford V regimen. For the 11% of pts in whom front line therapy fails, secondary therapy is effective with a DSS of > 80%. The majority of pts (84%) failed at distant sites suggesting that more aggressive upfront chemotherapy may have been beneficial in these pts. Future efforts will aim at identifying this subset upfront. Pts who relapse within a year have a worse outcome despite salvage and for this subgroup, newer therapies are warranted. Disclosures: Horning: Genentech: Employment.


Blood ◽  
2006 ◽  
Vol 107 (1) ◽  
pp. 52-59 ◽  
Author(s):  
Martin Hutchings ◽  
Annika Loft ◽  
Mads Hansen ◽  
Lars Møller Pedersen ◽  
Thora Buhl ◽  
...  

Abstract Risk-adapted lymphoma treatment requires early and accurate assessment of prognosis. This investigation prospectively assessed the value of positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose (FDG-PET) after two cycles of chemotherapy for prediction of progression-free survival (PFS) and overall survival (OS) in Hodgkin lymphoma (HL). Seventy-seven consecutive, newly diagnosed patients underwent FDG-PET at staging, after two and four cycles of chemotherapy, and after completion of chemotherapy. Median follow-up was 23 months. After two cycles of chemotherapy, 61 patients had negative FDG-PET scans and 16 patients had positive scans. Eleven of 16 FDG-PET–positive patients progressed and 2 died. Three of 61 FDG-PET–negative patients progressed; all were alive at latest follow-up. Survival analyses showed strong associations between early FDG-PET after two cycles and PFS (P < .001) and OS (P < .01). For prediction of PFS, interim FDG-PET was as accurate after two cycles as later during treatment and superior to computerized tomography (CT) at all times. In regression analyses, early interim FDG-PET was stronger than established prognostic factors. Other significant prognostic factors were stage and extranodal disease. Early interim FDG-PET is a strong and independent predictor of PFS in HL. A positive early interim FDG-PET is highly predictive of progression in patients with advanced-stage or extranodal disease.


2021 ◽  
Vol 5 (18) ◽  
pp. 3647-3655
Author(s):  
Phoebe T. M. Cheng ◽  
Diego Villa ◽  
R. Petter Tonseth ◽  
David W. Scott ◽  
Alina S. Gerrie ◽  
...  

Abstract Radiotherapy (RT) is typically incorporated into the treatment of limited-stage nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), although it remains unknown whether chemotherapy alone may be suitable in select patients. We evaluated outcomes of limited-stage NLPHL at BC Cancer on the basis of era-specific guidelines: routine RT era, 1995 to 2005 (n = 36), combined modality with 2 cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy followed by RT or RT alone; positron emission tomography (PET) era, after 2005 (n = 63), ABVD alone (4 cycles) if the PET scan after the second cycle of ABVD (PET2) is negative, or treatment is changed to RT if PET2 is positive. Median age of patients was 38 years (range, 16-82 years), 73% were male, and 43% had stage II. With a median follow-up of 10.5 years for all patients, 5-year progression-free survival (PFS) was 93% and was 97% for overall survival (OS), with no difference by treatment era (PFS, P = .13; OS, P = .35). For the 49 patients who had a PET2 scan, 86% were PET negative and 14% were PET positive by Deauville criteria with 5-year PFS rates of 92% and 80% (P = .70), respectively. This is the largest study of a PET-adapted approach in NLPHL and supports that ABVD alone may be a viable option in select patients with a negative PET2 scan, with consideration of acute and long-term toxicities.


2016 ◽  
Vol 34 (12) ◽  
pp. 1376-1385 ◽  
Author(s):  
Pier Luigi Zinzani ◽  
Alessandro Broccoli ◽  
Daniela Maria Gioia ◽  
Antonio Castagnoli ◽  
Giovannino Ciccone ◽  
...  

Purpose The clinical impact of positron emission tomography (PET) evaluation performed early during first-line therapy in patients with advanced-stage Hodgkin lymphoma, in terms of providing a rationale to shift patients who respond poorly onto a more intensive regimen (PET response-adapted therapy), remains to be confirmed. Patients and Methods The phase II part of the multicenter HD0801 study involved 519 patients with advanced-stage de novo Hodgkin lymphoma who received an initial treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and who underwent an early ifosfamide-containing salvage treatment followed by stem-cell transplantation if they showed a positive PET evaluation after two cycles of chemotherapy (PET2). The primary end point was 2-year progression-free survival calculated for both PET2-negative patients (who completed a full six cycles of ABVD treatment) and PET2-positive patients. Overall survival was a secondary end point. Results In all, 103 of the 512 evaluable patients were PET2 positive. Among them, 81 received the scheduled salvage regimen with transplantation, 15 remained on ABVD (physician’s decision, mostly because of minimally positive PET2), five received an alternative treatment, and two were excluded because of diagnostic error. On intention-to-treat analysis, the 2-year progression-free survival was 76% for PET2-positive patients (regardless of the salvage treatment they received) and 81% for PET2-negative patients. Conclusion Patients with advanced-stage Hodgkin lymphoma for whom treatment was at high risk of failing appear to benefit from early treatment intensification with autologous transplantation, as indicated by the possibility of successful salvage treatment in more than 70% of PET2-positive patients through obtaining the same 2-year progression-free survival as the PET2-negative subgroup.


Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2412
Author(s):  
Mariana Bastos Oreiro ◽  
Reyes Martín ◽  
Pilar Gomez ◽  
Nieves López Muñoz ◽  
Antonia Rodriguez ◽  
...  

The optimal strategy for early surveillance after first complete response is unclear in Hodgkin lymphoma. Thus, we compared the various follow-up strategies in a multicenter study. All the included patients had a negative positron emission tomography/computed tomography at the end of induction therapy. From January 2007 to January 2018, we recruited 640 patients from 15 centers in Spain. Comparing the groups in which serial imaging were performed, the clinical/analytical follow-up group was exposed to significantly fewer imaging tests and less radiation. With a median follow-up of 127 months, progression-free survival at 60 months of the entire series was 88% and the overall survival was 97%. No significant differences in survival or progression-free survival were found among the various surveillance strategies. This study suggests that follow-up approaches with imaging in Hodgkin lymphoma provide no benefits for patient survival, and we believe that clinical/analytical surveillance for this group of patients could be the best course of action.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 764-764 ◽  
Author(s):  
Andreas Engert ◽  
Carsten Kobe ◽  
Jana Markova ◽  
Heinz Haverkamp ◽  
Peter Borchmann ◽  
...  

Abstract Abstract 764 Introduction The role of additional radiotherapy after chemotherapy for advanced-stage Hodgkin lymphoma is unclear. The German Hodgkin Study Group (GHSG) thus performed the HD15 trial in which advanced-stage Hodgkin lymphoma patients having residual disease after 6–8 cycles of BEACOPP were evaluated by 18F-fluorodesoxyglucose positron emission tomography (PET) following chemotherapy. Methods Entry criteria for the PET question in HD15 were partial remission (PR) after the end of chemotherapy with at least one involved nodal site measuring more than 2.5 cm in diameter by computed tomography (CT). Exclusion criteria included diabetes, elevated blood sugar levels and skeletal involvement with risk of instability. Calculations were restricted to those cases with either progressive disease (PD) or relapse within 12 months after PET or at least 12 months of follow-up. A total of 2,137 patients with de novo HL were included in HD15 of whom 728 had a tumor bulk ≥ 2.5 cm after BEACOPP chemotherapy and were qualified for the PET question. An expert panel performed the assessment of response and PET. Only PET-positive patients were scheduled for radiotherapy of residual disease. The negative prognostic value (NPV) of PET was defined as the proportion of PET-negative patients without progression, relapse or radiotherapy despite being PET-negative within 12 months. Results The full analysis set included 728 patients of whom 699 had at least 12 months of follow-up. Median age was 30 years, 57% were males and 66% had NS histology. Of the 728 qualified patients with residual disease ≥ 2.5 cm after BEACOPP, 74.2% were PET-negative and 25.8% PET-positive. In the PET-negative group, a total of 28 patients relapsed or had radiotherapy despite being PET-negative (8 patients including 1 relapsing patient) resulting in a negative prognostic value of 94.6% (95% CI 92.7% to 96.6%). With a median follow-up of 38 months, the time-to-progression after PET at 3 years was 92.1% for PET-negative patients counting radiotherapy as failure and 86.1% for PET-positive patients (95%-CI for difference -11.9% to -0.1%). Overall, only 11% of patients had additional radiotherapy as compared to 71% after BEACOPPescalated in our prior HD9 trial. In addition, there was no difference in PFS or overall survival as compared to our earlier trials in advanced-stage HL. Discussion The NPV of PET of 0.95 suggests that indeed only patients with residual disease after chemotherapy who are PET-positive need additional radiotherapy. PET-negative patients at least after BEACOPP can be spared from additional radiotherapy. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 589-589 ◽  
Author(s):  
Andreas Engert ◽  
Heinz Haverkamp ◽  
Carsten Kobe ◽  
Jana Markova ◽  
Christoph Renner ◽  
...  

Abstract Abstract 589FN2 Purpose: Intensified chemotherapy with eight cycles of BEACOPPescalated in advanced stage Hodgkin lymphoma (HL) is highly effective but also associated with relevant treatment related toxicity. In addition, the need for radiotherapy in this setting is unclear. To reduce toxicity without losing efficacy the German Hodgkin Study Group thus conducted the prospective randomized clinical HD15 trial investigating two less intensive chemotherapy variants, followed by positron emission tomography (PET) guided radiotherapy. Methods: Between January 2003 and April 2008, 2182 patients with newly diagnosed, histology-proven HL aged 18–60 years were included. Patients in Ann-Arbor stage IIB with large mediastinal mass or extranodal lesions, or those in stage III or IV were randomly assigned to receive either eight cycles of BEACOPPescalated (8Besc), six cycles of BEACOPPescalated (6Besc), or eight cycles of BEACOPP14 (8B14). After completion of chemotherapy, patients in partial response (PR) with a persistent mass measuring 2.5 cm or more were assessed by PET. Only patients who were positive on centrally-reviewed PET scan received additional radiotherapy (RT) with 30Gy. The study was designed to show non-inferiority for the primary endpoint, freedom from treatment failure (FFTF). Other endpoints included overall survival, tumor response, side effects of treatment and progression-free survival (PFS) after PET. Results: The full analysis set comprised 2126 patients, 705 with 8Besc, 711 with 6Besc and 710 with 8B14. Baseline characteristics were balanced between groups with a median age of 33 years and 334 patients (15.7%) in stage II disease. 682 patients (32.1%) had an International Prognostic Score (IPS) of 0–1, 1115 (52.4%) of 2–3, and 329 (15.5%) of 4–7. Hematological toxicities occurred in 92.4% (8Besc), 91.7% (6Besc), and 79.7% (8B14) of cases. After a median follow-up of 48 months, there were 53 deaths (7.5%) in the 8Besc group, 33 (4.6%) in the 6Besc group and 37 (5.2%) in the 8B14 group. The higher number of deaths in the 8Besc group mainly resulted from acute toxicity of chemotherapy (15 vs. 6 vs. 6) and secondary neoplasms (13 vs. 5 vs. 8). There were 72 secondary cancers including 29 secondary acute myeloid leukemias and myelodysplastic syndroms, 19 (2.7%) after 8Besc, 2 (0.3%) after 6Besc and 8 (1.1%) after 8B14. Complete response (CR) was achieved in 90.1% of patients after 8Besc, in 94.2% after 6Besc and in 92.4% after 8B14 (p=0.01). FFTF at 5 years was 84.4% in the 8Besc group, 89.3% in the 6Besc group (97.5% confidence interval (CI) for difference 0.5% to 9.3%), and 85.4% in the 8B14 group (97.5 CI −3.7% to 5.8%), respectively (see figure). Accounting for planned interim analyses, both 97.5 repeated CIs for the hazard ratio excluded the non-inferiority margin of 1.51 (8Besc vs. 6Besc, 0.44 to 1.02; 8Besc vs. 8B14, 0.62 to 1.36). Overall survival at five years was 91.9%, 95.3%, and 94.5%, and was also better with 6Besc compared to 8Besc (97.5% CI 0.2% to 6.5%). PFS results were similar to FFTF. Per-protocol and subgroup analyses supported the primary analysis. PET scans performed after chemotherapy were centrally reviewed in 822 patients of whom 739 were in PR with residual mass ≥ 2.5 cm having no other exclusion criteria. 548 patients were PET-negative (74.2%) and 191 were PET-positive (25.8%). Importantly, PFS was comparable between patients in CR or those in PET-negative PR after chemotherapy with 4-year PFS rates of 92.6% and 92.1%, respectively. Only 11% of all patients in HD15 received additional RT as compared to 71% in the prior HD9 study. Conclusion: Six cycles of BEACOPPescalated followed by PET-guided RT are more effective and less toxic compared to 8 cycles in patients with advanced stage HL. In particular, critical toxicities observed with 8 cycles where reduced with 6 cycles of BEACOPPescalated. PET performed after chemotherapy can guide the need of additional RT in this setting and reduces the number of patients requiring RT. Disclosures: No relevant conflicts of interest to declare.


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