Clinical trials in chronic myeloid leukemia (CML) are usually carried out in specialized centers whereas primary care for patients (pts) with CML is mainly provided by local oncology practices. The aim of this study was to assess treatment practices in pts with CML in the setting of private oncology practices in Germany. We collected data of 819 pts with a confirmed diagnosis (dx) of CML in 2013 or later from 43 practices. At dx, 84.2% ( n =690) and 9.4% ( n =77) of pts were in chronic or accelerated phase, 0.7% ( n =6) had a blast crisis. Molecular monitoring was provided by EUTOS certified laboratories in 87.7% of pts. Typical BCR::ABL1 transcripts were detected in 86.6% ( n =709). Molecular response was assessed after 2.8, 6.0, 9.4 and 12.9 m (mean) after start of treatment. Of the pts with available data, 11.1% did not achieve early molecular response and at 18 m, 83.7% had at least a major molecular response. 288 (35.2%) of pts switched to 2 nd line (2L) treatment after a mean of 21.0 months. Reasons for 2L treatment were side effects in 43.4% and suboptimal response or failure in 31.4% of pts. 106 pts went on to third line (3L) treatment. 36.8 % of pts switched to and 92.8 % of pts still on 3L treatment achieved BCR::ABL1 IS ≤1% at 12 m. In conclusion, in Germany pts with CML are routinely monitored by qPCR and good responses are achieved in the majority. Treatment changes are mainly due to adverse events rather than suboptimal responses.

Purpose The WHO 2016 re-classification of myeloproliferative neoplasms resulted in a separation of essential thrombocythemia (ET) from the pre-fibrotic and fibrotic (overt) phases of primary myelofibrosis (MF). This study reports on a chart review conducted to evaluate the real life approach regarding clinical characteristics, diagnostic assessment, risk stratification and treatment decisions for MPN patients classified as ET or MF after implementation of the WHO 2016 classification. Methods In this retrospective chart review, 31 office-based hematologists/oncologists and primary care centers in Germany participated between April 2021 and May 2022. Physicians reported available data obtained from patient charts via paper–pencil based survey (secondary use of data). Patient features were evaluated using descriptive analysis, also including diagnostic assessment, therapeutic strategies and risk stratification. Results Data of 960 MPN patients diagnosed with essential thrombocythemia (ET) (n = 495) or myelofibrosis (MF) (n = 465) after implementation of the revised 2016 WHO classification of myeloid neoplasms was collected from the patient charts. While they met at least one minor WHO-criteria for primary myelofibrosis, 39.8% of those diagnosed with ET did not have histological BM testing at diagnosis. 63.4% of patients who were classified as having MF, however, did not obtain an early prognostic risk assessment. More than 50% of MF patients showed characteristics consistent with the pre-fibrotic phase, which was emphasized by the frequent use of cytoreductive therapy. Hydroxyurea was the most frequently used cytoreductive medication in 84.7% of ET and 53.1% of MF patients. While both ET and MF cohorts showed cardiovascular risk factors in more than 2/3 of the cases, the use of platelet inhibitors or anticoagulants varied between 56.8% in ET and 38.1% in MF patients. Conclusions Improved histopathologic diagnostics, dynamic risk stratification including genetic risk factors for cases of suspected ET and MF are recommended for precise risk assessment and therapeutic stratification according to WHO criteria.

Abstract 2633 Background: Today, most patients with Hodgkin Lymphoma (HL) can be cured at first diagnosis. For HL patients suffering from relapse or progression after first line therapy, high dose chemotherapy followed by autologous stem cell transplant (ASCT) is the treatment of choice and cures about 50% of these patients. Those who relapse or progress after ASCT have a very poor prognosis and clearly represent an area of unmet medical need. However, data on this small group of patients is rather limited and no established risk factors are available. Here, we present a recent retrospective analysis from the GHSG database to better characterize HL patients with relapse or progression after ASCT in order to define possible risk factors for the prediction of overall survival. Methods: All trials in the GHSG database were searched for HL patients who relapsed or progressed after ASCT. The information for this retrospective analysis was updated in May 2012. Overall survival after progression of HL following ASCT (OSrr) was the end point of this study. Descriptive statistics and Kaplan Meier estimates of OSrr were used and risk factors for OSrr analyzed. The significance level was set to 0.05. Results: 152 patients who relapsed or progressed with HL after ASCT were identified. 149 patients fulfilled the predefined inclusion criteria. With a median observation time of 65 months after progression, 112 patients (75%) had died. OSrr was 63% (95% confidence interval [CI]; 54% to 70%), 51% (95% CI 42% to 58%), and 20% (95% CI 13% to 28%) at 1, 2 and 5 years, respectively. From several risk factors tested, stage (p=0.044) and presence of B-symptoms (p=0.005), both at relapse before ASCT, significantly predicted OSrr. Combination of these two risk factors allowed the identification of three distinct risk categories for the 4 significantly different groups (p=0.013; Figure 1). Accordingly, patients in clinical stage I or II without B-symptoms had a somewhat better prognosis (OSrr 84% [95% CI 67% to 92%], 72% [95% CI 54% to 84%] and 33% [95% CI 18% to 49%] at 1, 2 and 5 years, respectively). Other potential risk factors such as stage at first diagnosis (p=0.80), early, late or multiple relapses before ASCT (p=0.95), and time from ASCT to further progression of HL (p=0.81) were not significant. Conclusions: Current treatment approaches for patients with relapsed or progressive HL after ASCT show disappointing results with 80% of this very high-risk group dying within 5 years. Emerging new drugs such as brentuximab vedotin might improve the outcome of these patients in the future. Disclosures: von Tresckow:Takeda Pharma GmbH: Honoraria, Travel Grants Other. Borchmann:Millenium The Takeda Oncology Company: Research Funding; Takeda Pharma GmbH: Travel Grants, Travel Grants Other. Engert:Millenium The Takeda Oncology Company: Honoraria.

Depending on stage and risk factor profile, up to 95% of patients with Hodgkin lymphoma at first presentation reach complete remission after the initial standard treatment including radiotherapy, combination chemotherapy or combined modality therapy. Patients who relapse after first complete remission can achieve a second complete remission and long-term disease-free survival with salvage treatment including radiotherapy for localized relapse in previously nonirradiated areas, conventional salvage chemotherapy, or high-dose chemotherapy with stem cell transplantation. In general, risk-adapted treatment strategies are used in the treatment of patients with Hodgkin lymphoma. Adequate staging of newly diagnosed patients enables optimal treatment planning, which is of particular importance for finding a balance between treatment efficacy and toxicity. In this review, an overview is given of the current knowledge of clinical and biological risk factors and the role of imaging modalities during and after treatment.

PURPOSE:To determine whether epoetin alfa reduces anemia-related fatigue, improves other aspects of health-related patient-recorded outcomes (PROs), reduces the number of RBC transfusions, and has an impact on freedom from treatment failure (FFTF) and overall survival (OS) in patients with advanced-stage Hodgkin's lymphoma (HL).PATIENTS AND METHODS:The prospectively randomized HD15EPO study performed by the German Hodgkin Study Group investigated epoetin alfa administered at doses of 40,000 U weekly during and after chemotherapy (six to eight cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone [BEACOPP]) in a double-blind, placebo-controlled setting. The study accrued 1,379 patients, of whom 1,328 were assessable for safety, 1,303 were assessable for clinical outcome, and 930 were assessable for PROs.RESULTS:PROs were not different in patients receiving placebo or epoetin alfa, both after the end of chemotherapy and 6 months thereafter. There was no difference between patients treated with epoetin alfa or placebo with respect to FFTF and OS. There were also no differences in the numbers of deaths, progressions, relapses, and thromboembolic events. The median number of RBC transfusions was reduced from four per patient in the placebo group to two per patient in the epoetin alfa group (P < .001), with 27.4% of patients needing no RBC transfusion in the placebo group compared with 36.7% of patients in the epoetin alfa group (P < .001).CONCLUSION:Epoetin alfa administered at 40,000 U weekly parallel to BEACOPP chemotherapy was safe in patients with advanced-stage HL and reduced the number of RBC transfusions but had no impact on fatigue and other PRO domains.

PURPOSE:High-dose chemotherapy (HDCT) followed by autologous stem-cell transplantation (PBSCT) has become the standard treatment for patients with relapsed Hodgkin's lymphoma (HL). The intensity of treatment needed is unclear. This European intergroup study evaluated the impact of sequential high-dose chemotherapy (SHDCT) before myeloablative therapy.PATIENTS AND METHODS:Patients with histologically confirmed, relapsed HL were treated with two cycles of dexamethasone, cytarabine, and cisplatin, and those without disease progression were randomly assigned. In the standard arm (A), patients received myeloablative therapy with carmustine, BEAM (carmustine, etoposide, cytarabine, and melphalan) followed by PBSCT. Patients in the experimental arm (B) also received sequential cyclophosphamide, methotrexate, and etoposide in high-doses before BEAM. Freedom from treatment failure (FFTF) was the primary end point. Remission rates, overall survival (OS), and toxicity of treatment were secondary end points.RESULTS:From a total of 284 patients included, 241 responding patients were randomly assigned after two cycles of dexamethasone, cytarabine, and cisplatinum. Patients treated in arm B had longer treatment duration and experienced more toxicity and protocol violations (P < .05). Mortality was similar in both arms (20% and 18%). With a median observation time of 42 months, there was no significant difference in terms of FFTF (P = .56) and OS (P = .82) between arms. FFTF at 3 years was 62% (95% CI, 56% to 68%) and OS was 80% (95% CI, 75% to 85%). Patients with stage IV, early relapse, multiple relapse, anemia, or B symptoms had a higher risk of recurrence (P < .001).CONCLUSION:Compared with conventional high-dose chemotherapy, additional SHDCT is associated with more adverse effects and does not improve the prognosis of patients with relapsed HL.

BACKGROUND Using a parametric carcinogenesis model, we disentangle the superimposing effects of primary and relapse therapies of Hodgkin's disease on secondary neoplasias. PATIENTS AND METHODS We analyze eight randomized trials of the German Hodgkin's lymphoma study group [5357 individuals, 67 secondary acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) and 97 secondary non-Hodgkin's lymphoma (NHL)]. Primary therapies were divided into four groups: radiotherapy alone, moderately dosed COPP/ABVD-like chemotherapies for intermediate and advanced stages and BEACOPP escalated. RESULTS For secondary AML/MDS, the hazards after primary therapies are proportional (maximum at 3.4 years), while the hazard after relapse therapy is more peaked (maximum at 1.8 years). Intermediate and advanced stage chemotherapy resulted in a cumulative risk of 1.5%, while the risk after BEACOPP escalated is higher (4.4%, P = 0.004) and comparable with that after relapse therapy (4.5%). For secondary NHL, there are no differences in cumulative risk between the primary therapies (2.9%), while the risk after relapse therapy is increased (6.6%, P = 0.002). CONCLUSIONS BEACOPP escalated moderately increases the risk of secondary AML/MDS but not NHL. No differences were found between other chemotherapies of advanced stages and intermediate stages. Secondary AML/MDS occurs faster after relapse treatment than after primary treatment.

For older patients with early unfavorable or advanced stage Hodgkin lymphoma (HL) the prognosis is much worse than for younger HL patients. We thus developed a new regimen, BACOPP (bleomycin, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone), to improve both tolerability and efficacy of treatment for older HL patients. Between 2004 and 2005, 65 patients with early unfavorable or advanced stage HL aged between 60 and 75 years were enrolled in this phase 2 trial. Treatment consisted of 6 to 8 cycles of BACOPP. Residual tumor masses were irradiated. Primary endpoints were feasibility as determined by adherence to protocol and overall response rate. Secondary endpoints included toxicity, freedom from treatment failure, and progression free and overall survival. For the final analysis 60 patients (92%) were eligible; 75% of treatment courses were administered according to protocol. World Health Organization grade 3/4 toxicities occurred in 52 patients. Fifty-one patients (85%) achieved complete remission, 2 (3%) partial remission, and 4 (7%) developed progressive disease. With a median observation time of 33 months, 18 patients died (30%), including 7 treatment-associated deaths. Three patients died before response assessment. Thus, the BACOPP regimen is active in older HL patients but is compromised by a high rate of toxic deaths. This trial was registered at www.clinicaltrials.gov as #NCT00284271.

8615 Background: High-dose chemotherapy followed by autologous stem cell transplantation is an established treatment option for patients with relapsed or refractory non-Hodgkin’s lymphoma (NHL). Recently, radioimmunotherapy has emerged as a new treatment modality for B-cell NHL with the combined benefits of immunotherapy and radiotherapy. The incorporation of Yttrium-90 ibritumomab tiuxetan into a high-dose chemotherapy conditioning regimen promises to improve the outcome after autologous stem cell transplantation for relapsed or refractory NHL. Methods: A phase II trial to evaluate the safety and efficacy of combining Yttrium-90 ibritumomab tiuxetan with high-dose carmustine, cytarabine, etoposide, and melphalan (BEAM) conditioning chemotherapy and autologous stem- cell transplantation in patients with relapsed or refractory NHL. Patients with either relapsed, refractory or transformed follicular lymphoma (FL) or relapsed, refractory diffuse large B cell lymphoma (DLBCL) were eligible. All patients received a sequential high-dose regimen including rituximab as salvage chemotherapy. Results for the first 10 out of a planned 20 patients are reported. Results: The median age was 57 years. 7 patients had DLBCL, 2 had FL, and 1 patient had a transformed FL. The median number of relapses was 1 (range 1–3). After a median time of follow up of 11 months (range 1 to 26 months) 2 patients relapsed. Interestingly, both patients had central nervous system relapse. One of these patients died. Adverse events were similar to those seen historically with high-dose BEAM alone. There were no treatment-related deaths or secondary malignancies. Conclusions: Theses preliminary results suggest that the combination of Yittrium-90 ibritumomab tiuxetan and BEAM followed by autologous stem cell transplantation is safe and effective for the treatment of patients with relapsed or refractory NHL. No significant financial relationships to disclose.

BACKGROUNDInfertility is one of the most significant side-effects in long-term survivors of successfully treated Hodgkin's lymphoma (HL).PATIENTS AND METHODSThe fertility status was assessed in male HL patients enrolled into trials of the German Hodgkin Study Group from 1988 to 2003.RESULTSIn pre-treatment analysis (n = 202), 20% of patients had normozoospermia, 11% azoospermia and 69% had other dyspermia. In post-treatment analysis (n = 112), 64% of patients had azoospermia, 30% other dyspermia and 6% normozoospermia (P < 0.001). Azoospermia was observed in 90% of patients treated with chemotherapy alone, 67% of those treated with combined modality and 11% of those treated with radiotherapy alone (P < 0.001). Azoospermia was more frequent after 4x cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine, dacarbazine (COPP/ABVD) (91%), 8x bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone (BEACOPP) baseline (93%) and 8x BEACOPP escalated (87%) compared with 2x COPP/ABVD (56%; P = 0.003). There was a statistically significant difference in post-treatment follicle-stimulating hormone (FSH) levels between patients with azoospermia and those with preserved spermatogenesis (P = 0.001).CONCLUSIONSDepending on the treatment received, male HL patients are at high risk of infertility after treatment. FSH might be used as surrogate parameter for male fertility in future studies.

Methods: We conducted consecutive audits in the South West of England, encompassing 22 hospitals, for the years 1993 (96 cases), 1999 (93) and 2005 (148), to examine the patient diagnostic and treatment pathways and long term outcomes. These unselected cohorts included all HL known to the diagnosing hospital. The number of participating units varied between the three audits and an accurate estimate of the underlying population and ASI of HL was not possible from the data obtained. Complete SWPHO cancer registry data for the same periods were therefore examined.

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.

Anemia is frequent among cancer patients and impacts organ function and quality of life of those affected. Anemia has been shown to be a negative prognostic factor in several malignancies including Hodgkin Lymphoma (HL). In addition, the advent of more aggressive treatment regimen such as BEACOPP escalated has resulted in more HL patients needing red-blood-cell transfusion. Thus, apart from the chemotherapy-related question of the GHSG HD15 trial, ie 8 cycles of BEACOPP escalated or 6 cycles of BEACOPP escalated or 8 cycles of BEACOPP14, patients in HD15 were randomized between Epoetin-α and placebo. Study drug was given at 40.000 I.E. weekly with a hemoglobin target level of 12–13g/dl. Primary endpoint was fatigue after the end of chemotherapy (CT) and 6 months later measured with the EORTC QLQ-C30 questionnaire (0–100 scale). With respect to the more recent safety discussion related to erythropoetins (EPOs) in general, we also analyzed efficacy and safety endpoints although the trial was not sufficiently powered for time-to-event analyses. Between1/2003 and 12/2006 1.379 patients were randomized for the EPO question of whom 1.329 were eligible. Of these 1.286 (96.8%) are fully evaluable. Patient characteristics were balanced between the placebo and the EPO arm. In those 688 patients who were randomized before 7/2005 and eligible for analysis, the CR/CRu rate was 90, 6% with a median follow-up of 28 months, 58 progressions/relapses (8.4%) and 33 deaths (4.8%) without differences between study arms. There was also no difference in terms of freedom from treatment failure (hazard ratio (HR) 0.9, 95%-confidence interval (CI) 0.6–1.4) and overall survival (HR 1.1, 95% CI 0.6–2.3). 51 serious adverse (7.4%) and 35 thrombovascular events (5.1%) were observed with no significant difference between arms. The median number of red blood cell units given significantly favored patients receiving Epoetin-α (2 vs 4; test for trend p<0.001). The interim analysis for fatigue gave an average value of 61+/−25.8 (mean +/−SD) at the end of treatment and a reduced fatigue score of 33+/−25.3 at six months after CT.

To date, there is little information on the impact of more aggressive treatment regimen such as BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) on the fertility of male patients with Hodgkin lymphoma (HL). We evaluated the impact of BEACOPP regimen on fertility status in 38 male patients with advanced-stage HL enrolled into trials of the German Hodgkin Study Group (GHSG). Before treatment, 6 (23%) patients had normozoospermia and 20 (77%) patients had dysspermia. After treatment, 34 (89%) patients had azoospermia, 4 (11%) had other dysspermia, and no patients had normozoospermia. There was no difference in azoospermia rate between patients treated with BEACOPP baseline and those given BEACOPP escalated (93% vs 87%, respectively; P > .999). After treatment, most of patients (93%) had abnormal values of follicle-stimulating hormone, whereas the number of patients with abnormal levels of testosterone and luteinizing hormone was less pronounced-57% and 21%, respectively. In univariate analysis, none of the evaluated risk factors (ie, age, clinical stage, elevated erythrocyte sedimentation rate, B symptoms, large mediastinal mass, extranodal disease, and 3 or more lymph nodes) was statistically significant. Male patients with HL are at high risk of infertility after treatment with BEACOPP.

Fourth interim analysis of the HD R2 study, a european multicenter trial for patients with relapsed Hodgkin lymphoma