Elderly Hodgkin Lymphoma Patients Research Articles

Prescription Patterns of Initial Therapy and Outcomes of Elderly Hodgkin Lymphoma Patients. Toxicity and Efficacy Balance of Attenuated Initial Therapy

Introduction Patients (pts) older than 60 years of age diagnosed with classic Hodgkin lymphoma (cHL) have worse prognosis than younger pts, including complete remission rates (CR) as well as lower progression free (PFS) and overall survival (OS). Age over 70 years, along with comorbidities, has been identified as a factor conferring additional worse prognosis. We sought to evaluate the prescription patterns and outcomes of pts ≥70y in comparison with “younger” elderly cHL pts diagnosed 60-69y. Methods We conducted a retrospective review of newly diagnosed cHL patients treated at our academic medical center between 2012-2022. Baseline and treatment characteristics, including planned and unplanned dose reduction events were collected from electronic medical records. Outcomes included disease response to initial therapy, PFS, OS and non - relapse mortality (NRM). All analyses were done using R and its packages. Differences between age groups were evaluated using Fisher and Wilcoxon rank-sum tests. PFS and OS were calculated using the Kaplan Meier method, comparisons done using log-rank. The cumulative incidence of NRM was calculated considering relapse as a competing risk, comparisons evaluated with Gray's test. Results We identified 81 pts ≥60 years (y) diagnosed with cHL, 37 of whom were ≥70y. Among baseline characteristics, more pts ≥70y had ECOG performance status ≥2 (30 vs. 9%, p = 0.05), and all had at least one comorbidity, compared with 77% in pts 60-69y (p = 0.002); other baseline characteristics were comparable, and the numerical difference in the rates of individual comorbidities did not reach statistical significance (table 1). A statistically significant higher proportion of pts ≥70y had planned de-intensification of their treatment (46% vs. 16%, p = 0.007), most commonly this corresponded by prescription of the doxorubicin, vinblastine and dacarbazine (AVD) as initial therapy, use of brentuximab vedotin alone or in combination with non-anthracycline containing regimens. One pt in the younger cohort did not receive therapy and died within two weeks of diagnosis. Subsequent dose reductions occurred in both age groups and pts ≥70y had a higher proportion of pts with overall reduced treatment intensity (i.e., planned + unplanned) (n = 22, 59% vs. n = 14, 33%, p = 0.024). Among pts treated with systemic therapy (n = 80), overall response rates were 73% and 85% for ≥70y and younger pts, respectively (p = 0.42). Complete response (CR) rates were 70% and 81% (p = 0.23). For pts treated with an anthracycline containing regimen, CR rates were 78% for pts ≥70y and 83% for pts 60 - 69y (p = 0.77). After a median follow up of 53 months (IQR 32-71), 18 (23%) pts had progression of their disease after initial therapy and 18 (23%) pts had died. Median progression free survival had not been reached for both groups, and four-year estimates were 65% for pts ≥70y (95% CI 51-85%) and 83% for pts 60 - 69y (95% CI 73-95%), this difference did not reach statistical significance (p = 0.08). Similar results were observed for PFS when the analysis was limited to pts treated with anthracycline-containing regimens (4-year PFS: ≥70y = 68% vs. 60-69y = 85%, p = 0.06). Median OS was not reached for both groups, four-year estimates were 75% for pts ≥70y (95% CI 61-92%) and 90% for pts 60-69y (95% CI 81-100%) (p =0.007), with comparable results when pts treated with anthracycline were studied (4-year OS: ≥70y = 75% vs. 60-69y = 92%, p = 0.003). Analysis of the cumulative incidence of NRM (with relapse as competing risk) showed there were no significant differences among pts ≥70y (1-year 5.8% [95% CI 1-17%]) vs. 60-69y (4.7% [95% CI 1-14%]) (p = 0.2) (figure 1). Conclusions Patients diagnosed with cHL at ages ≥70 years have more comorbidities and more often have worse performance status than pts 60-69y. Older pts more often are treated with attenuated regimens and/or require dose reductions/discontinuation after starting therapy. While the dose reductions and modifications limit NRM to rates comparable to those of younger pts, PFS and OS remain lower for pts ≥70y, suggesting long - term disease control is inferior in this patient subgroup. Systematic prospective studies of attenuated but more effective regimens are needed in cHL pts diagnosed at advanced age.

Overall survival and causes of death in elderly patients with Hodgkin lymphoma: a Norwegian population-based case-control study.

Elderly Hodgkin lymphoma (HL) patients are poorly characterized and under-represented in studies. In this national population- based study, we investigated cause-specific survival using competing-risk analysis in elderly HL patients compared to the normal population. Patients ≥60 years of age diagnosed between 2000-2015 were identified by the Cancer Registry of Norway, and records were reviewed in detail and compared to data from the Norwegian Cause of Death Registry for patients and cancer-free controls. Of 492 patients, 81 (17%) were ineligible for treatment directed specifically towards HL, mostly because of an underlying other lymphoma entity, whereas 74 (15%) and 337 (69%) were treated with palliative or curative intent, respectively. Median overall survival in patients ineligible for assessment of HL-directed therapies was 0.5 years (95% Confidence Interval [CI]: 0.4-0.6), and for palliatively and curatively treated patients 0.8 (0.4-1.2) and 9.1 (7.5-10.7) years, respectively. After correction of discrepancies in registry data, with 359 deaths, 108 (30%) died of HL, the most common cause of death. In curatively treated patients, treatment-related mortality was 6.5% and the risk difference of dying from HL compared to controls was 28% (95% CI: 23-33%) after ten years. These numbers indicate disease control in a majority of elderly patients eligible for curative treatment, compared to risk differences for death from HL of 59% (48-71%) and 42% (31-53%) after ten years in the palliative and ineligible groups, respectively. There was an increased risk of dying from hematologic malignancies other than HL in all groups, but not from other competing causes of death, showing no excess mortality from long-term treatment complications.

Clinical Dilemmas in the Treatment of Elderly Patients Suffering from Hodgkin Lymphoma: A Review.

Elderly patients make up a significant number of cases of newly diagnosed Hodgkin lymphoma. However, unlike in young patients, the outcomes of elderly patients are poor, and they are under-represented in phase III trials. Prior to treatment initiation, geriatric assessment should ideally be performed to address the patient's fitness and decide whether to pursue a curative or palliative approach. The ABVD regimen is poorly tolerated in unfit patients, with high treatment-related mortality. Alternative chemotherapy approaches have been explored, with mixed results obtained concerning their feasibility and toxicity in phase II trials. The introduction of brentuximab vedotin-based regimens led to a paradigm shift in first- and further-line treatment of elderly Hodgkin lymphoma patients, providing adequate disease control within a broader patient population. As far as checkpoint inhibitors are concerned, we are only just beginning to understand the role in the treatment of this population. In relapsed/refractory settings there are few options, ranging from autologous stem cell transplantation in selected patients to pembrolizumab, but unfortunately, palliative care is the most common modality. Importantly, published studies are frequently burdened with numerous biases (such as low numbers of patients, selection bias and lack of geriatric assessment), leading to low level of evidence. Furthermore, there are few ongoing studies on this topic. Thus, elderly Hodgkin lymphoma patients are hard to treat and represent an unmet need in hematologic oncology. In conclusion, treatment needs to be personalized and tailored on a case-by-case basis. In this article, we outline treatment options for elderly Hodgkin lymphoma patients.

Adverse Events in Elderly Hodgkin Lymphoma Patients Treated with Pembrolizumab or Nivolumab in the Real World

Introduction: Registry data indicate that 20% or more of Hodgkin lymphoma (HL) patients are ≥60; these HL patients have been labeled as elderly as their treatment has been associated with more toxicity, a higher relapse rate, and greater mortality relative to younger patients. The characteristics of HL in elderly patients differ from those in younger patients and may represent a biologically more aggressive disease. Further, elderly patients generally have a greater comorbidity burden than their younger counterparts, which may contribute to their under-representation in clinical trials. Nivolumab (NIVO) and pembrolizumab (PEMBRO) are both approved for treating relapsed/refractory HL based on studies that largely enrolled younger patients, as only about 10% of enrolled patients in the pivotal trials that led to their United States (US) Food and Drug Administration (FDA) approval were ≥60 years of age. Whether adverse events (AEs) related to these immunotherapies differ between younger and older HL patients is unknown and may have important clinical and practice implications. Therefore, we reviewed all post-marketing case reports from the FDA Adverse Events Reporting System (FAERS) Database involving NIVO or PEMBRO for HL and compared AEs and outcomes by age. Methods: The FAERS database is a repository of anonymized reports for product-related AEs, classified using the Medical Dictionary for Regulatory Activities (MedDRA) and categorized as serious or non-serious. The database was queried for cases involving NIVO or PEMBRO (and their respective trade names) from the FDA approval date for the HL indication (May 17, 2016 for NIVO; March 14, 2017 for PEMBRO) through March 31, 2019. Cases were excluded if the age of the patient was unknown, or if the case was reported outside the US. Comparisons of rates of AEs by age group were made using Fisher's exact test; statistical significance was determined at a two-sided α=0.05. Results: A total of 126 cases were retrieved (117 involving NIVO, 9 involving PEMBRO). One hundred and fourteen of the 126 cases (90%) were categorized as serious. Median age of all patients involved was 56 (range 10-89); 53 of the cases (42%) involved patients age 60 or older (Table). Overall, 8 cases had an outcome categorized as life-threatening; 20 cases resulted in death; 2 resulted in disability; and 74 resulted in hospitalization. A higher proportion of cases involving younger patients were categorized under the reaction group "neoplasms benign, malignant and unspecified" (16% vs. 2%; p<0.01), and older patients had a greater incidence of infectious complications compared with their younger counterparts, though this was marginally significant (40% vs. 23%; p=0.05). The proportion of cases resulting in hospitalization was significantly higher in the ≥60 age group as compared to the <60 age group (79% vs. 44%; p <0.01). Adverse reactions that were common in clinical trials, such as fatigue, pyrexia, headache, peripheral neuropathy, upper respiratory tract infection, hypothyroidism, diarrhea, nausea and vomiting, did not show any significant associations by age group (all p values >0.05). Conclusions: Although elderly patients comprise 20% of the HL patient population in the US, our post-marketing analysis indicates that AEs in this subgroup account for more than 40% of the total. This suggests that elderly HL patients experience a disproportional number of AEs compared to younger HL patients. While the types of AEs reported in post-marketing cases generally paralleled those observed in clinical trials of HL patients receiving NIVO or PEMBRO, hospitalizations and infections were more common in the elderly group. These differences in the adverse reactions and safety outcomes associated with PD-1 blockade therapy in HL patients may help inform clinical care and monitoring for AEs. Despite the inherent limitations of this study, our findings complement clinical trial safety data and provide insight into real-world trends in reported safety signals that merit further study. Disclosures Zettler: Cardinal Health: Employment. Nabhan:Aptitude Health: Employment. Gajra:Cardinal Health: Employment. Feinberg:Cardinal Health: Employment.

A Phase II Study of Brentuximab Vedotin (BV) in the Treatment of Elderly Hodgkin Lymphoma (HL) Patients at First Relapse or with Primary Refractory Disease — FIL_BVHD01

Older age (≥60 years) has consistently been identified as an independent adverse prognostic factor for Hodgkin lymphoma (HL) survival in population-based studies and clinical trials in the last several decades. Elderly HL patients are significantly underrepresented in clinical trials and have a markedly inferior prognosis compared with younger patients. Brentuximab vedotin (BV) is an antibody-drug conjugate linking the microtubule-disrupting agent monomethylauristatin E to an anti-CD30 antibody. BV monotherapy yields an objective response rate (ORR) of 75% in relapsed HL, with a subset of patients having durable remissions at 5 years. In a retrospective analysis of BV activity in patients aged ≥60 years with relapsed HL, ORR was 56%. Although higher rates of adverse events (AEs) such as anemia, fatigue, and neuropathy were seen in older compared with younger patients, BV was tolerable overall, and a significant proportion of older patients had clinical benefit. Based upon this favorable experience, our phase II study evaluated the efficacy and safety of BV as a single agent in elderly patients at first relapse or with primary refractory HL. This was a single-arm, open-label, multicenter, clinical trial. The primary endpoint of this study was the ORR. Main secondary endpoints were: duration of response, complete remission rate, progression free and overall survival at 1 year and type, incidence, severity, seriousness, and relatedness of any adverse events occurring during the study period. ClinicalTrials.gov identifier NCT02227433.Twenty patients were enrolled, 2 results in screening failure and 1 patient was treated in protocol violation (more of 1 previous therapy). Eighteen patients were considered for safety analysis, whereas 17 subjects were included in the efficacy analysis. BV (1.8 mg/kg) was administered as a single IV infusion on Day 1 of each 21-day cycle for a maximum of 16 cycles.Three patients interrupted BV treatment before the first scheduled restaging (right after the IV cycle): 2 due to toxicity and 1 due to clinical progression of disease (PD). At first restaging, ORR was 52.9% (4 complete response [CR] and 5 partial response [PR]). Eight patients proceeded till the second restaging (VIII cycle) with and ORR of 17.7% (1 CR and 2 PR). Only 2 patients completed all the 16 scheduled cycles: they achieved finally a CR and a PR, respectively. These two patients are still in response at the latest available follow up. Seven patients had early treatment discontinuation due to toxicity, mainly due to neuropathy grade II-III (3 out of 7).The objective of the study, i.e. at least 13 responses, was not reached and BV doesn't seem to be an effective single agent for elderly HL patients at first relapse. Nevertheless, prolonged disease control (more than 12 months) was registered in two patients, suggesting that some subjects can benefit from this salvage treatment. DisclosuresZinzani:Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Pharmaceuticals: 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, Speakers Bureau; PFIZER: 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; MSD: Honoraria, Speakers Bureau; Astra Zeneca: Speakers Bureau; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; SERVIER: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees.

Hodgkin lymphoma in elderly patients.

We aim to summarize the current knowledge on the treatment of elderly Hodgkin lymphoma patients with a focus on evidence from clinical trials and novel drugs. For elderly Hodgkin lymphoma patients above 60 years without precluding comorbidities a curative treatment approach is warranted. Early favorable stage patients should receive two cycles of multiagent chemotherapy followed by 20 Gy localized radiotherapy. Early unfavorable stage patients should receive four cycles of multiagent chemotherapy followed by 30 Gy localized radiotherapy. For advanced stage patients six cycles of multiagent chemotherapy can be recommended and should be followed by localized radiotherapy on residual disease manifestations. Relapsed or refractory patients should be treated in an individually tailored approach that considers both the patient's objectives and comorbidities. The antibody-drug conjugate brentuximab vedotin is a very effective option for elderly patients with a high response rate albeit limited durability. Anti-programed cell death protein 1 antibodies might also be effective in elderly Hodgkin lymphoma patients with a mechanism of action distinct from chemotherapy. In conclusion, the goal of treatment in newly diagnosed elderly Hodgkin lymphoma patients is curative whenever possible and prospective and retrospective evidence has shown that this is feasible for all disease stages with a variety of multiagent chemotherapy regimen. Relapsed and refractory elderly Hodgkin lymphoma patients can mostly only be treated with the goal of palliation. However, it remains to be seen if novel substances and new combination regimen are able to change that.

Outcomes of Chemotherapy Treatment in Elderly Patients with Hodgkin Lymphoma

Introduction: Hodgkin lymphoma (HL) is a common lymphoid malignancy accounting for approximately 10 percent of all lymphomas. In the United States (US), the incidence of HL has a bimodal distribution curve with peaks at age 20 years and a second peak at approximately age 65 years. Age of diagnosis is an important prognostic marker in HL with younger patients having superior outcomes. Patients diagnosed at greater than age 60 years are considered elderly. Prior analyses of HL treatment in elderly patients have revealed worse outcomes in this population with reported 5-year progression free survival (PFS) and overall survival (OS) from 30-45% and 40-60% ranges, respectively (Evens, Blood 2012). The most common first line treatment for HL is doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Elderly patients are thought to have higher risk of bleomycin toxicity and worse outcomes with treatment in comparison to younger patients. Omission of bleomycin or doxorubicin from chemotherapy regimens administered to elderly patients is not uncommon. This study evaluated treatment outcomes of HL in an elderly U.S. Veteran population.Methods: The VHA database was used to identify patients diagnosed with HL using ICD-03 codes C000-C8099, 9651, 9652, 9653-9655, 9663-9667, 9650, 9661-9662, and 9659. Data was available from the Veterans Affairs Central Cancer Registry (VACCR) from October 1st, 2001-December 31st 2013. Data was obtained on patient demographics, weight, height, other clinical characteristics, date of diagnosis and HL directed treatments. Chemotherapeutic agents patients received were collected from the VACCR data and missing data was abstracted using chart review. Patients who received at least one dose of any chemotherapy for HL were considered to have received chemotherapy. Of patients who received chemotherapy, those who received at least one dose of bleomycin or doxorubicin were included in the bleomycin and doxorubicin groups respectively. Patients less than age 60 years were excluded. Patients greater than age 60 years were stratified by age into age groups 61-69 and ≥70 years. Overall survival was measured from date of diagnosis to date of death. Kaplan-Meier method for overall survival was used to evaluate each treatment group. Cox proportional hazard model was used to evaluate risk of death after adjusting for age (61-69 years used as reference) and chemotherapy used (bleomycin or doxorubicin).Results: There were 1,135 unique HL patients [632 (56%) patients ≤ age 60 years, 503 (44%) patients >age 60 years] identified in the VHA database. For patients age years >60, 389 patients (77%) received chemotherapy; with 226 (58%) patients age years 61-69 and 163 (42%) age years ≥70. Bleomycin was administered to 177 (78%) patients age years 61-69 and 106 (65%) patients age years ≥70 (p=0.037). Doxorubicin was administered to 198 (88%) patients age years 61-69 and to 122 (75%) patients age years ≥70 (p=0.0012). Cox proportional hazards analysis demonstrated that patients ≥70 years had a worse overall survival (HR = 1.71; 95% CI 1.276-2.293) in comparison patients age 61-69 years. After adjusting for age and chemotherapy, treatment with doxorubicin (HR 0.67; 95% CI 0.416-1.084) or bleomycin (HR 0.77; 95% CI 0.512-1.192) was associated with an improved survival.Conclusions: This retrospective analysis represents the largest cohort of elderly HL patients with detailed treatment information reported to date. Advanced age (age ≥70 years) was confirmed to be a poor prognostic factor. The chemotherapy agents used in elderly patients also differed by age with less doxorubicin and bleomycin administered to patients age ≥70 years in comparison to those age years 61-69. While not statistically significant, this study demonstrated improved survival in patients receiving bleomycin or doxorubicin regardless of age. Further analyses adjusting for patient comorbidities, evaluating for treatment related toxicity (i.e. pulmonary toxicity) and accounting for cause specific mortality are pending. DisclosuresReagan:Seattle Genetics: Research Funding. Carson:Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

Tolerability and Efficacy of Treatments in Elderly Patients with Hodgkin Lymphoma: A Report from the Nebraska Lymphoma Study Group

Introduction: Approximately 20% of classical Hodgkin lymphoma (HL) patients are greater than 60 years old at diagnosis. The survival of this subgroup is inferior to that of younger patients, despite most being treated with curative intent. Possible reasons for this difference include: comorbidities, toxicity of treatment (especially bleomycin, Stamatoullas at al. BJH 2015), poorer baseline performance status, different disease biology, and more frequent chemotherapy dose reductions. Recent advances and refinements in treatment have not improved the outcomes of elderly patients with HL significantly (Johnson and McKenzie. Blood 2014). Selection of a regimen for HL should take comorbidities into account. There is not a clear standard of care treatment regimen for elderly patients with HL.Methods: Patients were treated by physicians of the Nebraska Lymphoma Study Group between 6/1983 and 6/2014. There were 119 patients with biopsy-proven HL who were 60 years of age or older at the time of diagnosis. The Kaplan-Meier method was used to estimate overall survival distributions and the log-rank test was used to compare survival distributions between groups. Comparisons of survival distributions were made using the log-rank test. Chi-square tests and t-tests were used to compare outcomes by treatments received. P-values less than 0.05 were considered to be statistically significant.Results: The mean age was 71 years (range 60.1 to 89.2). Mixed cellularity was the most common histological subtype (28.57%). Therapies given included: non-anthracycline based regimen ChlVPP in 36 patients (30.25%) and radiotherapy alone in 13 patients (10.92%); and anthracycline containing regimens ChlVPP-ABV in 35 patients (29.41%), Stanford V in 9 patients (7.56%) and ABVD in 26 (21.85%). Patients older than 70 did significantly worse OS p<0.001 (Figure 1). OS was not different with regards to stage at diagnosis I/II vs III/IV (p=0.3). Patients receiving an anthracycline containing regimen had a better OS than those receiving ChlVPP alone p<0.001 (Figure 2). In both, early stage (I-II) and late stage (III-IV) HL the best outcomes were seen either ABVD or ChlVPP-ABV. OS was inferior in patients who did not receive bleomycin or in those for whom it was stopped, as opposed to patients receiving full bleomycin planed doses p=0.029. Bleomycin was omitted in 6/70 patients, generally as a result of preexisting pulmonary comorbidities. Bleomycin was stopped/held during treatment in 18 patients (28.1%) because of concerns of toxicity. There were no deaths with a diagnosis of bleomycin lung injury in our series.Conclusions: HL patients performed worse with increasing age and patients above 70 years of age had a median survival of 4.6 years. Anthracyclines seem to be essential for optimal outcome, confirming a previous publication by our group (Weekes at al. JCO 2002). Either ABVD or ChlVPP-ABV appear to be equally effective in patients who can tolerate an anthracycline. Our results appear to compare favorably to other regimens tested in elderly HL patients: VEPEM-B tested in the UK (Proctor et al. Blood 2012) and the PVAG tested by the German group (Boll et al. Blood 2011). Although bleomycin is difficult to give to this population because of increased toxicity, patients who did not receive bleomycin or had it stopped during treatment had a poorer survival. Our results confirms the results of a recent publication from the German Group in which bleomycin omission in early-stage HL patients performed worse (Behringer at al. Lancet 2015). Certainly bleomycin is associated with pulmonary toxicity in this age group, although our incidence was not as high as reported in the North American Intergroup Trial (43%) with bleomycin administration for HL patients (Evens, Br J Haematol 2013). Though limited by the possible occurrence of selection bias conferred by the retrospective design, anthracycline-based regimens appear to be associated with better outcomes in elderly patients with HL. [Display omitted] [Display omitted] DisclosuresLunning:TG Therapeutics: Consultancy; Genentech: Consultancy; Gilead: Consultancy; Juno: Consultancy; BMS: Consultancy; Spectrum: Consultancy.

Advances in the treatment of Hodgkin lymphoma

In the past decades, Hodgkin lymphoma (HL) has turned from an incurable disease to one with the most favorable prognosis among adult malignancies. This is due to the introduction of effective multi-agent chemotherapy and the optimization of radiation techniques. At present, 80-90 % of patients achieve long-term remission when receiving appropriate first-line treatment. Even in case of relapse, up to 50 % can be successfully salvaged with high-dose chemotherapy and autologous stem cell transplantation. Thus, current studies do not necessarily aim at increasing treatment efficacy but rather focus on a possible reduction of acute and late toxicity by decreasing treatment intensity if possible. One promising strategy to spare therapy in good-risk patients is early response-adapted treatment stratification according to the result of interim positron emission tomography. The evaluation of novel drugs and the optimization of treatment for elderly HL patients and those with nodular lymphocyte-predominant HL are further aspects that are currently being addressed in ongoing trials. This review will give an overview on more recent clinical trials and discuss possible future strategies for the treatment of HL.

Progress in Hodgkin lymphoma: a population-based study on patients diagnosed in Sweden from 1973-2009

AbstractIn recent decades, attention has focused on reducing long-term, treatment-related morbidity and mortality in Hodgkin lymphoma (HL). In the present study, we looked for trends in relative survival for all patients diagnosed with HL in Sweden from 1973-2009 (N = 6949; 3985 men and 2964 women; median age, 45 years) and followed up for death until the end of 2010. Patients were categorized into 6 age groups and 5 calendar periods (1973-1979, 1980-1986, 1987-1994, 1994-2000, and 2001-2009). Relative survival improved in all age groups, with the greatest improvement in patients 51-65 years of age (P < .0005). A plateau in relative survival was observed in patients below 65 years of age during the last calendar period, suggesting a reduced long-term, treatment-related mortality. The 10-year relative survival for patients diagnosed in 2000-2009 was 0.95, 0.96, 0.93, 0.80, and 0.44 for the age groups 0-18, 19-35, 36-50, 51-65, and 66-80, respectively. Therefore, despite progress, age at diagnosis remains an important prognostic factor (P < .0005). Advances in therapy for patients with limited and advanced-stage HL have contributed to an increasing cure rate. In addition, our findings support that long-term mortality of HL therapy has decreased. Elderly HL patients still do poorly, and targeted treatment options associated with fewer side effects will advance the clinical HL field.

Phase 2 study of PVAG (prednisone, vinblastine, doxorubicin, gemcitabine) in elderly patients with early unfavorable or advanced stage Hodgkin lymphoma

AbstractApproximately 20% of all Hodgkin lymphoma (HL) patients are older than 60 years and have a poor prognosis, mainly because of increased treatment-related toxicity resulting in reduced overall dose intensity and more treatment-related mortality. To possibly improve the treatment of elderly HL patients, the German Hodgkin Study Group developed a new regimen, PVAG (prednisone, vinblastine, doxorubicin, and gemcitabine). In this multicenter phase 2 study, elderly HL patients in early unfavorable and advanced stages received 6 to 8 cycles of PVAG and additional radiotherapy if they were not in complete remission (CR) after chemotherapy. Endpoints included feasibility, acute toxicity, and response rate. Fifty-nine patients 60 to 75 years of age (median, 68 years) were eligible for analysis; 93% had advanced stage disease. WHO grade 3/4 toxicities were documented in 43 patients; 46 patients responded with CR/CR uncertain (78%). Within 37 months median observation time, 15 progressions or relapses and 17 deaths were observed, of which 8 were related to HL and 1 was the result of treatment-related toxicity. The 3-year estimates for overall survival and progression-free survival were 66% (95% CI, 50%-78%) and 58% (95% CI, 43%-71%), respectively. We conclude that PVAG is safe and feasible in elderly HL patients. This trial was registered at www.clinicaltrials.gov as #NCT00147875.

Relapsed Hodgkin Lymphoma in Elderly Patients: A Comprehensive Analysis From the German Hodgkin Study Group (GHSG)

Abstract 92▪▪This icon denotes a clinically relevant abstract Purpose:About 20% of all patients with Hodgkin Lymphoma (HL) are older than 60 years. They have a poor prognosis and often experience progressive or relapsed disease. To date, very little is known about second-line treatment, side effects and long-term outcome in elderly patients with progressive or relapsed HL. The German Hodgkin Study Group (GHSG) therefore carried out a comprehensive analysis of this interesting patient population. Out of 754 elderly HL patients treated within GHSG studies between 1993 and 2007, we identified those patients with documented disease progression or relapse and updated information on treatment, remission and survival status. Patients and Methods:115 patients with documented relapse or disease progression and a median observation time of 6 years were identified and included in the analysis. The patients' age at initial diagnosis ranged from 60 to 75 years (median 66 years), and 55% were male. Initially, most patients had mixed cellularity (46%) or nodular sclerosis (40%) subtype of HL. 53% of the patients had advanced stage disease according to the GHSG classification and 35% had not completed first line therapy as planned, mostly due to toxicity or progressive lymphoma (10% each). 27%, 31% and 42% had progressive disease, early and late relapse, respectively, and the median period between first diagnosis and first progression/relapse was 16 months. Results:Half of the patients received a curative treatment for relapsed disease, including conventional chemotherapy (ct) as ABVD or BEACOPP as well as high-dose ct. This approach resulted in CR/CRu in about 55% in this group of patients and median survival after first relapse/progression was two years. Interestingly, the outcome of the subgroup receiving conventional ct regimens was considerably better as compared to patients receiving high-dose ct (2.5 years difference in median survival after first relapse/progression). Palliative treatment, consisting of single-agent ct and/or radiotherapy or no therapy, was applied in about half of the patients. However, in these patients, median survival after first relapse/progression was only six months. Overall, a third line treatment was applied in 37 patients and 12 patients received a fourth treatment. In total, 99 patients died within the observation period (86%, 95%CI 78% to 92%): 63 patients (55%) of HL und 13 patients (11%) of treatment-associated toxicity. Overall, median survival after first relapse/progression was only 11 months in the analyzed group of patients. Conclusion:To our knowledge, this GHSG analysis provides by far the largest set of data published on relapsed/progressive HL of the elderly. In conclusion, the overall prognosis for these patients is very poor since less than 50% of the patients survive one year after relapse/progression. Obviously, there is a great medical need for older patients with relapsed HL. Our results should prompt further investigation and might be used to plan and design studies in this growing patient population. Disclosures:No relevant conflicts of interest to declare.

Feasibility and Efficacy of ABVD In Elderly Hodgkin Lymphoma Patients: Analysis of Two Randomized Prospective Multicenter Trials of the German Hodgkin Study Group (HD10 and HD11)

AbstractAbstract 418About 20% of all patients with first diagnosis of Hodgkin Lymphoma (HL) are older than 60 years. They have a poor prognosis mainly due to an increased toxicity of chemo- and radiotherapy. Although resulting in better disease control, aggressive regimens as BEACOPP are not feasible in this cohort of patients due to a treatment related mortality of up to 20%. Therefore, ABVD is considered treatment of choice for elderly HL patients, although prospective studies are lacking and current concepts mostly rely on cohort analyses. We therefore analyzed feasibility, safety and outcome of patients older than 60 years with early favorable- or early unfavorable-stage HL treated with 4 cycles of ABVD within the HD10 and HD11 trials of the GHSG. Sixty-eight and 49 elderly patients with a median age of 65 and 64 years were treated in HD10 and HD11, respectively. Early termination of protocol therapy was documented in 18% of HD10 patients, but only in 8% of HD11 patients, resulting in a lower relative total chemotherapy dose (RCD) in HD10. The relative dose intensity (RCD divided by total relative chemotherapy duration) was much lower in both studies compared to younger patients, due to more toxicity-related therapy delays and dose reductions, as 4 cycles of ABVD caused WHO grade III/IV toxicities in 67% (HD10) and 69% (HD11). Overall efficacy was significantly lower than in younger patients with an overall response rate of 90% in HD10 and 92% in HD11. The rate of relapsing patients was the same as in younger patients in HD11 (14%), whereas in HD10 it was much higher in the elderly (12%) which was mainly due to late relapses. Overall 22% and 37% of the patients died in HD10 and HD11, respectively (median observation time: 92 months). Besides other causes as cardiovascular disease (7%) or secondary neoplasia (5%), there was a high rate of deaths due to insufficient HL-control (5%) and treatment-related toxicities (5%). The 5-year PFS estimates for elderly patients were 79% (95% CI, 67% to 87%) in HD10 and 69% (95% CI, 54% to 80%) in HD11 compared to 96% (95% CI, 93% to 97%) and 86% (95% CI, 83% to 88%) for younger patients in HD10 and HD11, respectively. In conclusion, 4 cycles of ABVD are effective in elderly HL patients; however, treatment-related toxicity is high. Disclosures:No relevant conflicts of interest to declare.

Lenalidomide In Patients with Relapsed or Refractory Hodgkin Lymphoma.

AbstractAbstract 2828The immunomodulatory compound lenalidomide induces apoptosis in tumor cells, exerts antiangiogenic effects and activates immune effector cells. Apoptosis resistance, increased neoangiogenesis and impaired immunity critically contribute to Hodgkin's Lymphoma (HL). However, the activity of lenalidomide in HL is unknown so far.42 patients with multiple relapsed or refractory HL were treated with 25 mg oral lenalidomide for 21 days of a 28-day cycle in a named patient program in 18 different german hospitals. Participants gave written informed consent, had no curative treatment options, an ECOG performance status ≤ 2, and normal organ functions including peripheral blood counts within the normal range. Patients were staged and restaged with computed tomography (CT) of the initially involved sites; the use of PET was optional. Response was defined according to the “Cheson-criteria” from 1999 and evaluated after two to three cycles and every other cycle thereafter. Treatment was continued until disease progression or in case of intolerable toxicity occurred. Concomitant anti-thrombotic prophylaxis with 100 mg daily oral acetylsalicylic acid was mandatory. Patients with a history of thrombosis or thrombembolic events received low molecular heparin.To date, in the 24 patients who are eligible for analysis, treatment was well tolerated. No hematological or other toxicities above CTC grade-2 were reported; adverse events included diarrhea, constipation, neuropathy, and mild dyspnea. At restaging, eight of the analyzed patients had stable disease and twelve patients achieved clinical responses (11× PR, 1× CR) as measured by CT-scan. However, five of the heavily pretreated patients had progressive disease. Results on the remaining patients are currently being analyzed and will be presented at the ASH meeting.In conclusion, these first clinical observations indicate that lenalidomide is well tolerated and effective in patients with relapsed or refractory HL. Consequently, international clinical trials evaluating the role of lenalidomide in HL are in preparation and a phase I/II trial evaluating lenalidomide with AVD (Adriamycine, Vinblastine and Dacarbacine) in elderly HL patients is currently recruiting. Disclosures:Off Label Use: Lenalidomide approved for Multiple Myeloma and MDS (5q−).

PVAG (Prednisone, Vinblastine, Doxorubicin and Gemcitabine) In Elderly Patients with Intermediate or Advanced Stage Hodgkin Lymphoma: Final Results of a Phase II Study of the German Hodgkin Study Group (GHSG).

AbstractAbstract 2827About 20% of all patients diagnosed with Hodgkin lymphoma (HL) are older than 60 years. These patients have a rather poor prognosis, particularly when presenting in intermediate or advanced stages. Besides a biologically more aggressive disease, the main reason is a drastically increased toxicity of chemo- and radiotherapy resulting in a higher treatment-related mortality and insufficient dosing of the applied treatment. In the GHSG-HD9 trial, elderly patients did not benefit from the BEACOPP regimen in terms of overall survival due to a high toxicity related death rate. In order to improve tolerability, the PVAG regimen (prednisone, vinblastine, doxorubicin, and gemcitabine) was developed. This is a modification of the ABVD regimen in which bleomycin and dacarbazine were replaced by prednisone and gemcitabine. Here we report for the first time on the final analysis of this multi-center phase II study for elderly HL patients.61 patients were recruited between 2004 and 2007. 2 patients were excluded due to histology review not confirming HL, resulting in 59 patients with intermediate- or advanced-stage HL aged between 60 and 75 years. Treatment consisted of 6 cycles PVAG in patients achieving a complete remission (CR) after 4 cycles or 8 cycles PVAG in case of partial remission (PR) after 4 cycles. Patients who did not achieve CR after the end of chemotherapy received additional radiotherapy. Primary endpoints were administration of adequate dose without excessive delays, and response rate 3 months after end of treatment. Secondary endpoints included WHO grade III/IV toxicities, and occurrence of early progression.59 patients with a median age of 68 years were evaluated, of which 59% were male and 93% had advanced stage disease.The relative dose intensity (relative dose divided by relative chemotherapy duration) was at least 80% in 44 patients (76%). Regarding the single cycles, of which 85% started without major delay (max. 1 day), the mean relative dose of all agents was slightly decreasing over time but always exceeded 90%.WHO grade III/IV toxicities were documented in 43 patients (75%). Only 3 patients terminated CT because of excessive toxicity. 10 Patients (17%) received consolidating radiotherapy.In total, 46 patients responded with CR/CRu (78%; 95% CI: 65% to 88%), 2 with PR (3%), 2 with no change (3%) and 4 with progressive disease (7%). 3 patients died before restaging with unknown response and in 2 patients treatment outcome is unknown. With a median observation time of 37 months, 6 patients (10%) had progressive disease and 9 patients (15%) relapsed. In total, 10 patients died from relapsing or progressing HL, 2 from second malignancies (one of lung cancer after 23 months, and one of AML after 25 months) and 5 patients due to other reasons. Overall 17 patients (29%, 95% CI: 18% to 42%) have died so far.In conclusion, PVAG is safe and feasible in Hodgkin patients older than 60. The PFS indicates activity of this regimen in this poor prognosis patient cohort. However, a controlled randomized trial to determine the best treatment in this patient population is warranted.This trial was registered at www.clinicaltrials.gov as #NCT00147875. Disclosures:No relevant conflicts of interest to declare.

The Newly Developed Modified BEACOPP-Regimen (BACOPP) Is Active and Feasible in Elderly Patients with Hodgkin Lymphoma: Results of a Phase II Study of the German Hodgkin Study Group (GHSG)

Background: Approximately 20% of patients diagnosed with Hodgkin lymphoma (HL) are more than 60 years of age. These elderly patients still have a poor prognosis, especially when presenting with advanced stages and higher age. The main reason is underdosing of treatment, which is due to reduced tolerability of chemotherapy and age-related comorbidities. In the GHSG experience, elderly patients in the HD9 trial did not profit from the BEACOPP regimen in terms of overall survival, though a better HL specific freedom from treatment failure was achieved as compared to COPP/ABVD. Thus, the GHSG has developed the BACOPP regimen (bleomycin, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), in which etoposide was omitted to improve tolerability. Further modifications were a 1 week pretreatment phase with vincristine and prednisone, a limitation of vincristine in patients older than 65 years, an increase of the anthracyclines dose, and concomitant application of erythropoietin. Here we report on the final analysis of this multi-center phase II study for elderly patients.Methods: Between 2004 and 2005, 65 patients with HL in intermediate or advanced stages aged between 60 and 75 years were recruited. Treatment consisted of 6 cycles BACOPP in patients achieving a complete remission (CR) after 4 cycles or 8 cycles BACOPP in case of PR (partial remission) after 4 cycles. The primary endpoints were protocol adherence and response rates. Secondary endpoints included WHO grade III/IV toxicities, Kaplan Meier estimates of progression free survival (PFS), freedom from treatment failure (FFTF), and overall survival (OS).Results: Sixty patients (92%) were eligible for the final analysis. The majority of treatment courses (75%) were administered according to protocol. However, there was a tendency towards reduced dosing in cycles 5 to 8, especially for patients who had reached a CR after 4 cycles of BACOPP. In total, 51 patients showed CR/CRu (85%), 2 PR (3%) and 4 progression of disease (7%). Survival estimates and their 95% confidence intervals are shown in table 1.Table 1. Kaplan-Meier rates and 95% confidence intervals (CI) for FFTF, PFS and OS.time pointrate (%)CI (95%)FFTF12 months7361–8424 months6755–79PFS12 months7564–8624 months6856–80OS12 months8576–9424 months7665–87WHO grade III–IV toxicities were documented in 52 patients (87%). With a median observation time of 33 months, 18 deaths (30%) have been observed. Seven therapy associated fatal outcomes were documented.Conclusion: The new BACOPP regimen developed for elderly HL patients shows a high CR rate (85%). The FFTF rate at 2 years is within the range known from other schedules in this patient cohort. Overall, the regimen is feasible, but the therapy-associated death rate was high in our patient cohort. Thus, further studies and new approaches are still needed to substantially improve the outcome of elderly patients with early unfavorable or advanced stage HL.

ABVD Versus VEPEMB in Elderly Hodgkin's Lymphoma Patients.

BACKGROUND. In advanced age the prognosis of Hodgkin Lymphoma (HL) is poor. Aggressive regimens such as BEACOPP are toxic and difficult to apply in the elderly (Engert et al JCO 23, 5052, 2005). Moreover it is not clear if low intensive chemotherapy regimens are better than ABVD. The reduced intensity VEPEMB schedule showed good results in terms of efficacy and tolerance in a phase II multi-centre study (Levis et al Ann Oncol 15, 123, 2004).AIM OF THE WORK. To compare in HL elderly patients the reduced intensity VEBEMP schedule to the ABVD conventional one.PATIENTS AND METHODS. From June 2002 to December 2006, 54 HL patients older than 65 years entered the study. Frail patients were excluded. Patients were defined frail when present one or more of the following conditions: a) age higher than 80; b) three or more grade 3 comorbidities and/or one or more grade 4 co-morbidities according to the CIRS scale; c) activities of daily living (ADL) score less than 6; d) geriatric syndrome. Early stage (IA-IIA) patients were randomized between 3 courses of ABVD and 3 courses of VEPEMB, both of them followed by IF radiotherapy. Advanced stage (IIB-IV) patients were randomized between 6 courses of ABVD and 6 courses of VEPEMB, with radiotherapy limited to the areas of residual masses or of previous bulky disease. The VEPEMB regimen was as follows: vinblastine 6 mg/sqm i.v. on day 1, cyclophosphamide 500 mg/sqm on day 1, procarbazine 100 mg/sqm p.o. days 1 through 5, prednisone 30 mg/sqm p.o. days 1 through 5, etoposide 60 mg/sqm p.o. days 15 through 19, mitoxantrone 6 mg/sqm i.v. on day 15, bleomycin 10 mg/sqm i.v. on day 15. The regimen was scheduled every 28 days. ABVD was scheduled as usual. Growth factors (G-CSF and erythropoietin) were regularly considered for both regimens.RESULTS. Mean age was 72 (range 66–80). Seventeen patients (31%) were in early stage and the remaining 37 ones (69%) in advanced stage. One or more comorbidities were present in 26 cases (48%). Twenty six patients were allocated to ABVD and twenty eight to VEPEMB. Significant differences at diagnosis were not seen in terms of sex, mean age, stage, histology, co-morbidity and instrumental activity of daily living (IADL) score between the two arms. Significant differences in grade 3 or 4 toxicities were not seen between ABVD and VEPEMB arms: leucopenia 76% vs 82%; anemia 40% vs. 31%; mucositis 27% vs 19%; neurological toxicity 31% vs. 19%; infections 7% vs 23%. Toxic deaths were not observed. Treatment violations or interruptions were more frequent in the ABVD than in the VEPEMB arm, but this difference was not statistically significant (26% vs. 12%, p=ns). On an intention to treat analysis the final CR rate was slightly better in the ABVD than in the VEPEMB arm, even if this difference was not statistically significant: 86% vs. 77%. The 3-year relapse free survival rates were 57% and 50% (p=ns) for the ABVD and VEPEMB arm respectively. The 3-year overall survival and the event free survival rates for ABVD and VEPEMB were 79% vs. 60% (p=ns) and 52% vs. 24% (p=0.08) respectively.CONCLUSIONS. The prognosis of this group of elderly HL patients has been confirmed inferior to that observed in younger patients. ABVD is feasible with modest toxic cost in non-frail elderly patients and its results are at least equal, if not better, than those observed with the low intensive VEPEMB regimen.

Standard CHOP-21 as First Line Treatment for Elderly Patients with Hodgkin's Lymphoma.

Background: Outcome for elderly patients with Hodgkin's lymphoma is not as good as for younger patients, partly due to inferior capability to tolerate appropriate chemotherapy. There is no consensus on standard treatment. In 2000 we introduced CHOP-21 as standard chemotherapy for elderly Hodgkin's lymphoma patients at our institution with the aim to improve treatment results. CHOP-21 is known to be well tolerated in older patients with non-Hodgkin's lymphoma and contains active drugs for Hodgkin's disease.Patients and methods: Twenty-nine consequtive patients admitted to our institution from 2000–2004, 60 years and older with Hodgkin's lymphoma were included in this retrospective survey. Stage I/IIA patients received 2–4 cycles of CHOP-21 followed by 30–35 Gy involved field radiotherapy. Stage IIB-IV patients were treated with 6–8 cycles of CHOP-21. Selected cases received 30–35 Gy involved field radiotherapy against residual tumors.Results: The median age was 71 years (range 60–91). Sixty-two percent presented in stage IIB-IV and 38% in stage I-IIA. Forty-five percent of the early stage patients had bulky disease and/or elevated SR. For the advanced stage patients IPS score of 2–3 was the most common category (72%). B-symptoms occurred in 52% of the total population. Nodular sclerosis was the most frequent histology subgroup (38%), followed by mixed cellularity (17%). Fifty-five percent had co-morbidity prior to treatment, cardiac conditions were most common. Two cases of treatment-related deaths were seen (7%). The most common toxicity during therapy was febrile neutropenia (31%). Treatment modifications were necessary in 38% of cases. The complete response rate after CHOP +/− radiotherapy was as high as 93%. Median follow-up for the whole population is now three years. Five patients have relapsed, and four have died from Hodgkin's lymphoma. Total overall survival (OS) at three year was 80%, and better for the stage I-IIA subgroup (90% versus 60%). Total Hodgkin-specific survival (HSS) at three years was 73%, and 80% versus 60% for early and advanced stages, respectively. No relapses have occurred after 2 years.Outcome with CHOP +/− radiotherapy for Hodgkin's lymphoma patients 60 years and olderResponse29 pts (%)CR27 (93)PR1 (3)ORR28 (97)NE1 (3)Relapsed5 (18)Cause of deathHodgkin's lymphoma4 (14)Toxicity2 (7)Other1 (3)NE = not evaluable, patients died after one cycle of CHOP.Conclusion: The data shows that CHOP-21 is a well tolerated and highly effective first line treatment for elderly patients with Hodgkin's lymphoma. Of particular interest were the findings that advanced stage patients did so well and that no relapses have been seen after two years.

A New BACOPP Schedule Is Feasible and Effective in Elderly Hodgkin's Lymphoma Patients - Interim Results of a Multicenter Phase-II Trial of the German Hodgkin Study Group (GHSG).

Introduction:The outcome of Hodgkin's lymphoma (HL) patients (pts) increased over the last decades. However, treatment results in HL pts > 60 years are poor, particularly in patients with advanced stage disease. Large prospective studies are still lacking in this group. Based on the results for adult HL pts, we adapted the BEACOPP schedule for elderly HL pts with an increased dose of doxorubicin while omitting etoposide.Methods:From December 2003 to Mai 2005, 52 HL pts with a median age of 66 (range 61 – 75 years) and newly diagnosed HL in unfavourable clinical stage (CS) I, II and CS III, IV were prospectively recruited to receive 6 to 8 cycles of bleomycin (10 mg/m2), doxorubicin (50 mg/m2), cyclophosphamide (650 mg/m2), vincristine (1.4 mg/m2), procarbazine (100 mg/m2), and prednisone (40 mg/m2) (BACOPP) followed by local radiotherapy to residual lymphoma. Epoetin beta (30.000 IE once weekly) was administered to avoid therapy induced anaemia.Results:Up to day, 29 pts (14 males and 15 females) were evaluable for feasibility and response of treatment. Overall response rate after chemotherapy was 83% (38% CR and 45% PR). So far 2 pts (7%) developed progressive disease during chemotherapy. The treatment was generally well tolerated with WHO grade 4 toxicities: 31% leukopenia, 14% thrombopenia and 0% anaemia. Till now one patient died several weeks after treatment under sepsis.Conclusion:The first interim analysis of this new BACOPP schedule showed that this regimen is feasible in elderly HL pts. Full analysis of updated results will be presented.

Hodgkin's Lymphoma in Elderly Patients: A Comprehensive Retrospective Analysis From the German Hodgkin's Study Group

With improved prognosis for patients with Hodgkin's lymphoma (HL), interest increasingly focuses on high-risk groups such as elderly patients. We thus performed a retrospective analysis using the German Hodgkin's Study Group (GHSG) database to determine clinical risk factors, course of treatment, and outcome in elderly HL patients in comparison with younger adults. A total of 4,251 patients included in the GHSG studies HD5 to HD9 were analyzed, of whom 372 (8.8%) were 60 years or older and 3,879 (91.2%) were younger than 60 years. Patient characteristics, treatment results, toxicity, freedom from treatment failure (FFTF), and overall survival (OS) were compared. Elderly patients more often had mixed cellularity subtype, "B" symptoms, elevated erythrocyte sedimentation rate, and poorer performance status. Less frequently observed were nodular sclerosis subtype, large mediastinal mass, and bulky disease. Acute toxicity during chemotherapy was generally higher in elderly patients. This was most obvious for severe infections (grade 3 or 4; 15% v 6%) correlating with more severe leukopenia in elderly patients (grade 4; 38% v 23%). As a result, significantly fewer elderly patients received the intended full chemotherapy dose (75% v 91%). The survival analysis showed a significantly poorer treatment outcome for elderly patients in terms of 5-year OS (65% v 90%), FFTF (60% v 80%), and HL-specific FFTF (73% v 82%). Elderly patients have a poorer risk profile compared with younger HL patients and experience more severe treatment-associated toxicity. Higher mortality during treatment as well as lower dose-intensity are the major factors explaining the poorer overall outcome of elderly HL patients.