Indolente Lymphome/CLL/Hodgkin-Lymphome I

V501 Erstes Rezidiv eines Hodgkin Lymphoms nach zeitgemäßer Erstlinientherapie: Eine Analyse der Deutschen Hodgkin Studiengruppe (GHSG)
Paul Bröckelmann, Köln, D

Introduction: The relative benefit of targeted agents increasingly investigated and applied in relapsed or refractory Hodgkin lymphoma (rrHL) is difficult to estimate due to a lack of randomized trials. This retrospective study thus aimed at evaluating disease characteristics, treatment patterns and associated outcomes at first occurrence of rrHL after contemporary first-line treatment.

Methods: We retrospectively identified patients with sufficiently documented first rrHL initially receiving standard of care 1st-line treatment in the GHSG HD13-15 trials or for rrHL in the GHSG HDR3i trial. We assessed overall survival (OS) starting with date of 1st rrHL and ending with date of death for any reason and progression free survival (PFS) measured from date of rrHL to second rrHL or death from any reason. Patient, disease and treatment characteristics were analyzed with descriptive statistics and survival endpoints with Kaplan-Meier estimates.

Results: Of 437 patients with first rrHL identified, 402 patients with a median age of 37.5 years (18.4-76.8) and sufficiently documentated follow-up were assessed. Time to relapse was ≤12 months in 49% and stage III/IV rrHL present in 52% of patients. High-dose chemotherapy and autologous stem-cell transplantation (ASCT) with and without consolidation was administered in 20% and 52% of patients, respectively. The remaining 111 patients (27%) did not receive ASCT mostly due to insufficient response tosalvage chemotherapy, advanced age, localized disease or patients' preference. Overall, 10-year PFS and OS after first relapse were 48.2% (95%CI: 42.0%>54.4%) and 59.3% (95%CI: 53.2%>65.4%), respectively. Patients unsuitable for ASCT had less favorable 10y PFS (32.5%, 95%CI: 19.1%>45.9%) and OS (41.9%, 95%CI:28.1%>55.6%). Significantly inferior PFS and OS was also observed in primary refractory patients (10y PFS 36.0%,95%CI: 24.2%>47.9%; 10y OS 44.5%, 95%CI: 31.6%>56.6%) and those with stage IV disease at rrHL (10y PFS 29.3%, 95%CI: 18.5%>40.9%; 10y OS 39.6%, 95%CI: 27.9%>51.1%). Outcomes in these higher risk patients appeared more favorable with ASCT than without ASCT.

Conclusion: Our analysis of relapse and treatment patterns after contemporary HL therapy provides a robust benchmark to evaluate novel therapeutic strategies in rrHL. We confirm the curative potential of current rrHL treatments including non-ASCT approaches and roughly 50% of rrHL patients do not experience a consecutive relapse after 2nd-line treatment.

V634 Stadien-adaptierte Therapie des HIV-assoziierten Hodgkin Lymphoms: Langzeit-Ergebnisse einer prospektiven multizentrischen Studie
Marcus Hentrich, München, D

Introduction: Results from a prospective study on HIV-related Hodgkin lymphoma (HIV-HL) showed a 2-year overall survival (OS) of 90.7% with no significant difference between early favorable (95.7%), early unfavorable (100%) and advanced HL (86.8%) (JCO 2012;30:4117-23). However, the median follow- up was 26.2 months, and with longer follow-up survival rates may turn out to be less favorable.

Methods: Patients (pts) with early favorable HIV-HL received 2-4 cycles of ABVD + 30 Gy involved field (IF) radiation. In early unfavorable HIV-HL 4 cycles of BEACOPP baseline or 4 cycles of ABVD + 30 Gy IF were administered. 6 - 8 cycles of BEACOPP baseline were given in advanced stage HIV-HL. BEACOPP was replaced by ABVD in pts with advanced HIV-infection, and combination antiretroviral therapy (cART) was given concomitantly with chemotherapy (CT). Late relapse was defined as a relapse occurring > 2 years following the diagnosis of HL.

Results: Of 108 pts (8 females) included in the study, 23 (21%) had early favorable HL, 14 (13%) early unfavorable HL and 71 (66%) advanced stage HL. After a median follow-Up of 9.14 years (range, 0 - 12.9), there were 5 primary refractory HL (5%) and 11 relapses (10%), of which 8 were late relapses. 5 of these 16 pts (31%) are alive and in continuous complete remission, and 1 pt was under salvage CT at time of last follow-Up. A second primary malignancy (SPM) occurred in 11 pts after a median of 7.3 years (range, 1.5 - 10.7) from HL diagnosis. SPM were diffuse large B-cell lymphoma (n=2), peripheral T-cell lymphoma (n=1), anal cancer (n=3), larynx cancer (n=1), small cell lung cancer (n=1), urothelial cancer (n=1), and vulvar cancer (n=1). Overall, 22 pts (20%) have died. Causes of death were relapsed/refractory HL (n=9), neutropenic sepsis (n=5), SPM (n=3), unknown (n=2), an AIDS-defining illness (n=2), and sepsis unrelated to HIV or HL (n=1). The 10-year overall survival for pts with early favorable, early unfavorable, and advanced HL was 95.7%, 84.6%, and 76,1%, respectively. By univariate analysis, age ≥ 45 years [HR 2.97, P = 0.017) and extranodal involvement (HR 2.56, P = 0.04) was significantly associated with inferior OS while achievement of CR after CT (HR 0.035, P < 0.01) was associated with better OS.

Conclusions: Long term survival of pts with early unfavourable and advanced HIV-HL is slightly below the 2-year OS rates reported previously. However, the stage-adapted treatment strategy for HIV-HL remains appropriate.

V596 Young Investigator Award: Vorhersage von Tumor-assoziierter Fatigue bei Patienten mit Hodgkin Lymphom: Identifikation von Risikofaktoren
Nele Stadtbaeumer, Bielefeld, D

Introduction: Cancer-related fatigue (CRF) is one of the most distressing symptoms reported by cancer survivors. It commonly persists for years after treatment, compromising the survivors' quality of life. The etiology is complex and research focusses mainly on perpetuating factors. The aim of this study is to develop a prediction model for CRF of Hodgkin Lymphoma (HL) survivors. Therefore, we identify risk factors at the time of cancer diagnosis, as well as during and after therapy.

Methods: Data of N=4981 patients from diagnosis to year five of survival of the fifth study generation (HD13-15) of the German Hodgkin Study Group (GHSG) was analysed. Parametric (forward stepwise regression, lasso and all-pairs lasso) and non-parametric (bagged and boosted regression trees) machine learning algorithms were investigated to identify the relevant risk factors out of a set of 61 potential demographic, physical and psychosocial predictors. CRF was measured with the EORTC QLQ-C30.

Results: The all-pairs lasso algorithm performed best at detecting the relevant predictors in comparison to the other methods tested. All-pairs lasso identified eleven relevant risk factors which are able to predict CRF after therapy: overall life quality, age, physical and cognitive functioning, the financial impact, specific physical risk factors, cancer stage, and prior fatigue levels. Based on this variable selection we were able to estimate a regression model to predict the CRF level of HL survivors. Cross-validation showed that the baseline prediction model explains 31% of the variability of the CRF outcome.

Conclusions: Our analysis reveals relevant risk factors of CRF in HL survivors. The complex interplay between several demographic, physical and psychosocial predictors has some predictive power for the CRF level after therapy. The possibility of predicting CRF at the time of diagnosis and during and after therapy contributes to a better understanding of CRF in HL survivors and informs the development of much-needed interventions.

V192 Immunrekonstitution bei Patienten mit klassischer Haarzellleukämie unter der Therapie mit dem BRAF-Inhibitor Vemurafenib

Judith Konrat, Zürich, CH

Classical hairy cell leukemia (HCL) is a rare B-cell lymphoid malignancy associated with immunosuppression and is often complicated by pancytopenia or infection. Standard treatment options such as purine analogues (PA) achieve durable response but are associated with severe (temporary) immunosuppression. In particular, PAs cause long-lasting depletion of CD4+-lymphocytes and decrease of immunoglobulin G. The BRAF inhibitor vemurafenib is effective in HCL but its use in first line treatment is limited to selected clinical situations such as active infection. There is a lack of clinical data on the impact of BRAF inhibitors on immune function.

Here, we report the use of vemurafenib in 4 patients with HCL during the coronavirus disease 2019 (COVID-19) pandemic with detailed immune monitoring during treatment. All patients responded with normalization of peripheral blood counts. None of the patients developed severe infection. All patients had stable CD4+ T-lymphocyte levels (mean value: 205 cells/μl - 1301 cells/μl, min. value: 157 cells/μl, max. value: 1705 cells/μl, SD: 13 - 19%). One pretreated patient (patient 2, figure 1) had low CD4+ T- lymphocyte counts before treatment. Also, stable CD8+ T-lymphocyte levels were observed (mean value: 170 cells/μl - 831 cells/μl, min. value: 76 cells/μl, max. value: 1299 cells/μl, SD: 10 - 33%).

Immunoglobulin levels were normal in all patients without decline (range 7.5 g/l - 12.7 g/l). 3 out of 4 patients received the SARS-CoV-2 vaccination (Pfizer-BioNTech) during vemurafenib treatment. The IgG antibody levels against the spike-protein of SARS-CoV-2 were detectable in 3 out of 3 patients (2 - 12 weeks after the second vaccination).

Our findings suggest that BRAF inhibitors have limited effect on cellular and humoral immune function. The findings may support the use of BRAF inhibitors during the current pandemic to minimize COVID-19 related morbidity and mortality in patients without SARS-CoV-2 vaccination.


V176 Real-World-Daten von 1040 im Wiener Hämatologieverbund der Österreichischen Gesundheitskasse (ÖGK) behandelten und unbehandelten CLL-PatientInnen
Felix Keil, Wien, A

Introduction: In 2013 a haematology care network called the Hämatologieverbund der Österreichischen Gesundheitskasse (ÖGK), including the haematological department of the Hanusch hospital and three associated health care centres in Vienna was established. Depending on their disease specific demand (diagnosis, surveillance and active treatment) patients are treated either in the Hanusch hospital and/or in extramural health care centres. Due to the implementation of the outpatient centres, our network is able to provide care for 40% of the patients with haematological diseases in Vienna. The fluctuation to other haematological centres is low, thus we conclude that the data acquired from our patients is representative for analysis of real world data.

Methods: 1040 CLL patients who were diagnosed, observed and treated between 2012 and 2020 within our haematological network were analysed. Study data was generated by reviewing electronic and paper medical records. Comorbidities (Charlson Comorbidity Index - CCI, Cumulative Illness Rating Scale - CIRS) were assessed, additionally the Cockcroft-Gault formula (GFR) and cardiovascular risk assessment was performed in more detail. Furthermore, lines of treatment and treatment outcomes were evaluated.

Results: 52.6% of the patients were male, 47.4% female. The median age at diagnosis was 67.5 years. IGHV was mutated in 57.5% of patients, del(17p) was present in 9.9% of patients. 33% of the 1040 patients received CLL specific treatment. Treated patients underwent 1 to 6 lines of therapy (median: 1). 64.8% of patients in the CCI and 14.4% of patients in the CIRS showed no comorbidities at diagnosis. Interestingly according to the CCI, only 0.6% of patients were scored with renal comorbidity, whereas 13.6% of patients in the same population demonstrated an impaired GFR less than 60 ml/min. Cardiovascular assessment showed a 24.4% rate of arterial hypertension and a 10.1% rate of atrial fibrillation. Further details concerning comorbidities, treatment lines and outcome will be presented at the meeting.

Conclusion: One third of our CLL patients showed an indication for treatment. Established risk scores (CCI, CIRS) revealed conflicting data in regards to renal and cardiovascular comorbidities. The analysis of the Hämatologieverbund der ÖGK results in real world in- and outpatient data in subjects suffering from CLL.