The treatment of chronic lymphocytic leukemia (CLL) has shifted from chemoimmuno-therapy to targeted therapy, resulting in improved outcomes and patient survival. The aim of this study was to evaluate the efficacy and safety of venetoclax-based regimens in patients with relapsed/refractory CLL, as well as their effectiveness in patients previously treated with ibrutinib. We retrospectively analyzed 98 patients with CLL who received venetoclax in the second or later lines of therapy in Slovakia between 2018 and 2024. The median age was 68 years, and treatment was administered either as monotherapy or in combination with rituximab. Response to treatment was assessed according to the iwCLL 2018 criteria and clinical practice. Survival outcomes were evaluated using Kaplan–Meier analysis. An overall response was achieved in the majority of patients, with 2% achieving complete remission, 65% incomplete complete remission and 32% partial remission. At a median follow-up of 34 months, median overall survival was not reached (mean 52.5 months), and median progression-free survival was 46 months. Patients previously treated with ibrutinib had significantly worse outcomes (p = 0.022). Adverse events were predominantly hematological (64%), with 19% being grade 3–4. Venetoclax-based regimens represent an effective and well-tolerated treatment optionfor relapsed/refractory CLL, including in patients previously treated with ibrutinib, with acceptable and manageable toxicity.

BACKGROUND:Brentuximab vedotin combined with doxorubicin, vinblastine, and dacarbazine (A-AVD) improves outcomes in advanced-stage classic Hodgkin lymphoma, but patients with a positive early interim PET have inferior prognosis. We evaluated whether very early [18F]fluorodeoxyglucose ([18F]FDG)-PET-guided treatment adaptation after one cycle of A-AVD improves activity while limiting exposure to intensive chemotherapy. METHODS:This single-arm, multicentre, phase 2 trial was conducted at 16 centres in seven countries (the Netherlands, Spain, Denmark, Belgium, Portugal, Slovakia, and Poland). Adults aged 18-60 years with previously untreated advanced-stage classic Hodgkin lymphoma, WHO performance status 0-2, and adequate organ function received one cycle of A-AVD (brentuximab vedotin 1·2 mg/kg intravenously, doxorubicin 25 mg/m2 intravenously, vinblastine 6 mg/m2 intravenously, and dacarbazine 375 mg/m2 intravenously, all on days 1 and 15), followed by centrally reviewed [18F]FDG-PET-CT (PET1). PET1-negative (Deauville score 1-3) patients received five additional A-AVD cycles; PET1-positive (Deauville score 4-5) patients switched to six cycles of BrECADD (brentuximab vedotin 1·8 mg/kg intravenously on day 1; etoposide 150 mg/m2 intravenously on days 2-4; cyclophosphamide 1250 mg/m2 intravenously on day 2; doxorubicin 40 mg/m2 intravenously on day 2; dexamethasone 40 mg orally on days 2-5; dacarbazine 250 mg/m2 intravenously on days 3-4). The primary endpoint was 2-year modified progression-free survival (mPFS), defined as the proportion of patients alive and free of progression, relapse, or death from treatment start, with initiation of new systemic therapy for persistent disease counted as an event. Analyses were prespecified and conducted in the evaluable population (registered and eligible patients, who commenced the allocated treatment according to PET1 results after 1 cycle of A-AVD). The safety population consists of all patients who started A-AVD treatment (ie, received at least one dose of study therapy). This is the primary analysis of a completed trial. This trial is registered on ClinicalTrials.gov (NCT03517137) and EudraCT 2017-000498-35). FINDINGS:From Aug 1, 2019, to Aug 31, 2021, we enrolled 150 patients (81 males [54%] and 69 females [46%]; median age 32 years [IQR 23-39]) who received one cycle of A-AVD, after which 90 (60%) of them had a negative PET1 and 60 (40%) a positive result. 145 were evaluable for efficacy; the median follow-up at the clinical cutoff (Sept 1, 2023; database lock Dec 11, 2023) was 30·1 months (IQR 24·6-36·4). 16 patients experienced an mPFS event. The estimated 2-year mPFS was 89·5% (80% CI 85·7-92·4). The most common grade 3-4 adverse event was neutropenia (53 [35%] of 150) followed by anaemia (18 [12%]) and peripheral sensory neuropathy (nine [6%]). Serious adverse events occurred in 45 (30%) of 150 patients. No deaths occurred. INTERPRETATION:Very early PET-guided intensification with BrECADD yields high activity in advanced-stage classic Hodgkin lymphoma while sparing most patients intensive chemotherapy. FUNDING:Takeda Oncology.

642 Background: Salvage chemotherapy for relapsed testicular germ cell tumors (GCT) remains controversial, however, large retrospective series show higher cure rates with high-dose chemotherapy (HDCT) and peripheral blood stem cell transplant (PBSCT) compared to conventional dose chemotherapy (CDCT). Successful implementation of HDCT salvage treatment in high-volume centers is an important step towards achieving optimal cure rates in relapsed GCTs. Methods: 22 relapsed GCT patients were treated at National Cancer Institute in Slovakia with first (41%), second (54%) and third line (5%) salvage HDCT between 2014 and 2024. Median age at 1 st HDCT cycle was 33 years (range 21-55). Of the 22 patients, 3 (14%) had pure seminoma, 3 (14%) had primary mediastinal non-seminoma (PMNSGCT), 10 (45%) patients had cisplatin resistant disease, 7 (32%) and 15 (68%) of patients received 1 and 2 cycles of HDCT, respectively, 5 (23%) received maintenance oral etoposide and 6 (27%) had post-HDCT surgery. Indiana regimen consisted of 750mg/m2 etoposide and 700mg/m2 of carboplatin given on days -5,-4,-3 followed by PBSCT on day 0. Of 22 patients, 3 have received single dose CarboPEC (carboplatin, etoposide, cyclophosphamide) regimen in 2014 and 2015. Results: Median time between two cycles was 43 days (range 26-89) showing decreasing trend over the last years. 2-year PFS and OS were 40% (95% CI 0.19-0.61) and 34% (95% CI 0.13-0.55) and 5-year PFS and OS were 32% (95% CI 0.1-0.54) and 27% (0.06-0.48). Kaplan-Meier analysis produced inaccurate outcomes due to small sample size, currently 32% of patients is alive and disease-free. Predictors of unfavorable outcome were non-seminoma, NPMGCT, 1 cycle of HDCT, CarboPEC regimen and platinum resistant disease. Patients who underwent post-HDCT surgical resection had longer OS compared to patients unable to undergo surgery HR 4,85 (95% CI 1,69-13,9), p = 0.01 Patients receiving pre-HDCT bridging CDCT regimens had significantly worse OS compared to patients going directly to HDCT, HR 0 (95% CI 0-0), 5 year OS 19% vs 100%, p = 0.05. 10% of patients with cisplatin resistant disease is surviving beyond 5 years. There was one (4.5%) treatment-related death due to septic shock. Conclusions: HDCT is an effective salvage option in heavily pretreated relapsed GCTs. Our study suffers from weakness associated with small number of patients and selection biases. However, increasing expertise and timely delivery of HDCT results in cures in relapsed GCTs including cisplatin resistant subgroup.

Allogeneic stem cell transplantation (alloSCT) remains the established main treatment option with curative potential for many hematologic malignancies. We conducted a retrospective analysis of 104 adult patients who underwent alloSCT between March 2013 and November 2023. Kaplan-Meier survival analysis, the chi-square test, and Cox regression models were used to identify risk factors and outcomes. The median follow-up of the cohort was 19 (0.3-128.1) months. The median age of the recipients was 49 (19-65) years, and 57 (54.8%) recipients were males. Ninety (86.5%) patients had a matched sibling, and 14 (13.5%) had a haploidentical donor. According to the multivariable analysis, a body mass index (BMI) ≥30 kg/m2 (p=0.02) and status without chronic graft-versus-host disease (cGVHD) (p=0.04) were significantly associated with worse overall survival (OS). A BMI ≥30 kg/m2 was also predictive of worse relapse-free survival (p=0.01). The cumulative incidence rates of nonrelapse mortality (NRM) and relapse mortality (RM) at 1 year were 8.5% (95% CI: 4.3-16.5%) and 26.7% (95% CI: 19.1-37.4%), respectively. Patients without cGVHD had significantly higher RM than patients with cGVHD (p<0.001), whereas patients with cGVHD had significantly higher NRM (p=0.01). Patients with a BMI ≥30 kg/m2 had significantly more posttransplant fatal events (p<0.001). Our analysis revealed that a BMI ≥30 kg/m2 and a status without cGVHD were significantly associated with worse OS. NRM was higher in patients with cGVHD, whereas patients without cGVHD died mostly from relapses.

Introduction: The treatment landscape for chronic lymphocytic leukemia (CLL) has significantly evolved in recent years, transitioning from standard chemoimmunotherapy to targeted therapies with novel agents. Clinical trials have demonstrated improved efficacy and overall survival with these agents. However, question remain regarding treaatment sequencing, particularly the effectiveness of venetocalx in patients who have previosly recieved targeted therapies in earlier lines. The primary objective of this study was to evaluate the efficacy (maximum response) and safety of venetoclax-based regimens in secnd-line and later-line settings in patients with CLL treated at hemaology centers in Slovakia. the secondary objective was to asses the effectiveness of venetoclax in patients previously treated with ibrutinib. Methods: This retrospective analysis included 98 patients with CLL treated with venetoclax in second-line or subsequent lines of therapy across hematology centers in Slovakia from 2018 to 2024. Venetoclax was administered as monotherapy or in combination with rituximab. The median age at venetoclax initiation was 68 years (range: 49-83 years); 65 patients (66%) were male and 33(34%) female. Of these, 48 patients (49%) had prior exposure to ibrutinib. Treatment response and indications were assessed according to the 2018 International Workshop on CLL (iwCLL) criteria. Patients were evaluated after a minimum of two months of therapy until disease progression. Response was assessed via clinical evaluation, imaging (ultrasound or CT), and laboratory parameters. Bone marrow biopsies were not routinely performed. Adverse events were recorded based on CTCAE v5.0. Data were analyzed using descriptive statistics. Kaplan-Meier curves were used for overall survival (OS) and progression-free survival (PFS). Statistical comparisons used Chi-square, t-test, Mann-Whitney U, and Log-Rank test with a significance level of α = 0.05. Resutls: Venetoclax, both as monotherapy and in combination with rituximab, demonstrated high efficacy and an acceptable safety profile in patients with relapsed/refractory CLL. The overall response rate (ORR) was high: 67% patients achieved an unconfirmed complete remission (uCR), 32% patients achieved partial remission (PR), and 1 (1%) had no response. The median follow-up was 34 months. Median PFS was 46 months; median OS was not reached, with an estimated mean OS of 52.5 months. Paients previously treated with ibrutinib had significantly worse outcomes (p = 0.022): uCR in 56%, PR in 42%, with a median OS of 46 months vs 56 months and PFS of 40.6 months vs 48.8 months, compared to patients without prior ibrutinib exposure. These patients had a higher median number of prior treatment lines (3 vs 1.8) and were older (70 vs 66 years). Hematologic adverse events occured in 64% of patients (19% were grade 3-4); non- hematologic adverse events occured in 42%, though severity was not routinely graded. Conclusion: Our real-world data confirm that venetoclax-based regimens are highly effective and well tolerated in second-line and subsequent treatments of CLL, including in ptients previously treated with ibrutinib. Toxicity was manageable in the outpatient setting, with good treatment adherence and minimal need for hospitalization. these findings align with clinical trial data and support the continued intigration of venetoclax into the CLL treatment paradigm, offering patinets improved quality of life by avoiding the broader toxicity of traditional chemotherapy.

Conditioning regimens prior to hematopoietic stem cell transplantation (HSCT) are highly intensive and associated with significant toxicity, which can influence survival and quality of life. This study aimed to analyze the incidence of gastrointestinal, hematological toxicity, changes in quality of life, and cognitive functions in lymphoma patients undergoing autologous HSCT with BEAM/BeEAM conditioning. A total of 27 lymphoma patients indicated for autologous HSCT were enrolled in this prospective observational study from January 2020 to August 2023. Data collection was performed at admission and at the end of hospitalization, prior to discharge. Monitored parameters included laboratory tests (hematology and biochemistry), patient-reported quality of life assessed using the QLQ-C30 questionnaire, and perceived cognitive function evaluated using the FACT-Cog questionnaire. Mucositis of any grade occurred in 25 patients (92.6%), with diarrhea being the most common gastrointestinal symptom (any grade 85.2%, grade 3-4 37.0%). Diarrhea severity was generally independent of age, baseline blood counts, engraftment, weight loss, or hospitalization, except for an association between severe diarrhea and lower pre-transplant TSH (p=0.03). All patients experienced grade 1-2 weight loss, and 81.5% developed febrile neutropenia. Quality of life declined during transplantation, notably in role functioning, social functioning, and cognitive performance, alongside worsening fatigue, nausea/vomiting, pain, appetite loss, and diarrhea (all p-values <0.05). FACT-Cog scores showed no significant cognitive decline. The 2-year overall survival was 92.1% (95% CI 81.6-100%), while patients with SII >520.81 had lower survival (82.5%, 95% CI 60.4-100%, p=0.04), with higher SII significantly associated with worse outcomes. Autologous transplantation and the BEAM/BeEAM conditioning regimen are associated with considerable mucosal and hematologic toxicity. Patients are at risk of infections, nutritional deficits due to reduced intake, and deterioration in quality of life.

AbstractAimThe aim of this study was to analyse the outcomes of patients with large B‐cell lymphoma (LBCL) treated with chimeric antigen receptor T‐cell therapy (CAR‐Tx), with a focus on outcomes after CAR T‐cell failure, and to define the risk factors for rapid progression and further treatment.MethodsWe analysed 107 patients with LBCL from the Czech Republic and Slovakia who were treated in ≥3rd‐line with tisagenlecleucel or axicabtagene ciloleucel between 2019 and 2022.ResultsThe overall response rate (ORR) was 60%, with a 50% complete response (CR) rate. The median progression‐free survival (PFS) and overall survival (OS) were 4.3 and 26.4 months, respectively. Sixty‐three patients (59%) were refractory or relapsed after CAR‐Tx. Of these patients, 39 received radiotherapy or systemic therapy, with an ORR of 22% (CR 8%). The median follow‐up of surviving patients in whom treatment failed was 10.6 months. Several factors predicting further treatment administration and outcomes were present even before CAR‐Tx. Risk factors for not receiving further therapy after CAR‐Tx failure were high lactate dehydrogenase (LDH) levels before apheresis, extranodal involvement (EN), high ferritin levels before lymphodepletion (LD) and ECOG PS >1 at R/P. The median OS‐2 (from R/P after CAR‐Tx) was 6.7 months (6‐month 57.9%) for treated patients and 0.4 months (6‐month 4.2%) for untreated patients (p < 0.001). The median PFS‐2 (from R/P after CAR‐Tx) was 3.2 months (6‐month 28.5%) for treated patients. The risk factors for a shorter PFS‐2 (n = 39) included: CRP > limit of the normal range (LNR) before LD, albumin < LNR and ECOG PS > 1 at R/P. All these factors, together with LDH > LNR before LD and EN involvement at R/P, predicted OS‐2 for treated patients.ConclusionOur findings allow better stratification of CAR‐Tx candidates and stress the need for a proactive approach (earlier restaging, intervention after partial remission achievement).

Figure 1: Serum TARC levels for 96 individual patients at baseline and after one cycle of BV-AVD. The COBRA trial (EORTC-1537) is a fully enrolled, single-arm multicenter phase II study investigating the value of very early FDG-PET-response adapted Brentuximab Vedotin (BV)-based therapy for advanced stage classical Hodgkin Lymphoma (cHL). All patients received one cycle of BV, Doxorubicin, Vinblastine, and Dacarbazine (BV-AVD) followed by an early interim 18F-FDG-PET scan (iPET). Patients with a negative iPET by central assessment continued with five additional BV-AVD cycles, while iPET+ patients escalated to six cycles of BV, Etoposide, Cyclophosphamide, Doxorubicin, Dacarbazine, and Dexamethasone (BV-ECADD). The main objective of this trial is to assess whether treatment adaptation based on iPET results in improved efficacy while minimizing treatment toxicity. We here report baseline characteristics and iPET results after one cycle of BV-AVD. Deauville scores 4 or 5 were considered positive. In addition, we used ELISA to measure serum thymus and activation regulated chemokine (TARC) levels, which have been reported to reflect cHL disease activity and correspond with treatment response. TARC levels were measured both at baseline (bTARC) and after one cycle of BV-AVD (iTARC). A serum TARC level >1000 pg/ml was considered positive for detecting active disease (PMID 22058214). A total of 150 patients were included in the trial. Median age at inclusion was 32 years and 46% were females. Patients presented with stage IIB (15%), III (25%) or IV (60%) disease. Bulky disease was present in 56%. bTARC levels are currently available for 96 patients and were positive in 88 (92%), with a median level of 51831 pg/ml (range: 62–2033694). There were significant differences in bTARC levels across stages (p_value=0.044, F test), with bTARC levels lower for stage IIIA, as compared to IIB, IIIB or IV, but not with regards to bulky disease, age or gender. After one cycle of BV-AVD, iPET was positive in 40% of the patients. Within the group of patients with available iTARC and positive bTARC (n=84), iPET was positive in 33 cases (39%) and iTARC was positive in 12 cases (14%). Eight out of these 12 iTARC positive cases were also iPET positive. In conclusion, the majority of advanced stage Hodgkin patients showed a treatment response already after 1 cycle of BV-AVD, as measured by FDG-PET and serum TARC. FDG-PET quantification and tissue analysis for TARC expression are ongoing. These are preliminary data; definitive results will be presented at the symposium.

Background: Tyrosine kinase inhibitors (TKIs) have remarkably changed the management of Ph+ chronic myeloid leukemia (CML) and have dramatically contributed to substantial prolongation of survival rates and superior quality of life. However, long-term clinical experience with TKIs shows that despite the apparent therapeutic benefit, ~35% of CML patients exhibit primary resistance or intolerance to TKIs, and ~25% of those treated is forced to switch TKI at least once during therapy due to acquired resistance. Mutations in the kinase domain of BCR-ABL1 are the most comprehensively described mechanism of TKI-resistance but fail to explain ~40% of resistant cases. Nevertheless, due to the availability of several TKIs, the issue of TKI-resistance has de facto reduced to the mutation T315I and BCR-ABL1 independent resistance. TKI-resistance thus represents a persistent clinical problem to be solved and ultimately calls for alternative treatment solutions for CML patients with leukemic clones escaping TKI therapy. Oligonucleotide therapeutics have generated high expectation stemming from their potency and the field has seen great advancements leading to an apparent progress in clinical trials. Given the vastly different molecular target compared to protein inhibitors (RNA versus protein) as well as principally different mechanism of action, oligonucleotide therapeutics might represent rational and potent tools to combat TKI-resistant CML cells. Progress beyond the state-of-the art: The design of standard oligonucleotides is relatively straightforward and is sequence driven. However, the promiscuity of oligonucleotides places severe limitations on this approach since sequence-dependent off-target effects deteriorate their toxicological profile. Unconventionally, we considered additional parameters during the design of an oligonucleotide-based inhibitor, including steric and thermodynamic aspects of its binding to the target RNA, which significantly improved its safety. Here we report on a potent, safe, and highly specific oligonucleotide-based modality against BCR-ABL1 mRNA, ASP210, which effectively induces apoptosis in both BCR-ABL1 dependent and independent TKI-resistant CML cells. Methods:BCR-ABL1 positive cell lines MOLM-7 a CML-T1, both sensitive and resistant to TKIs imatinib and dasatinib were used to investigate the efficacy of ASP210, a biotinylated 34mer phosphorothioate DNA with an internal poly(ethylene glycol) linker. Briefly, MOLM-7 and CML-T1 cells and their resistant sub-lines were incubated with defined concentrations of ASP210 ranging between 0.25-5.0 µM for 10 days (applied once daily). Cell viability was monitored by trypan blue staining every day. The results were normalized to control, i.e., to untreated cells on the respective day. Of note, MOLM-7 TKI-resistant cells did not possess any mutation in the kinase domain, while both resistant sub-lines derived from CML-T1 harbored the clinically relevant mutation T315I. BCR-ABL1 negative cell line HL-60 was used as target negative control in the same experimental setup. Results:In vitro functional tests of ASP210 revealed its ability to induce cell death of all BCR-ABL1 positive cell types studied. A continuous decrease in the viability of ASP210-exposed cells has been observed already after 24 hours in all cell types including both TKI-sensitive CML cells and the derived TKI-resistant sub-lines irrespective of their T315I status. The efficacy of ASP210 was confirmed to be dose-dependent, with ASP210 causing a ~90% reduction of CML cells by day 5. Importantly, no effect on the viability of BCR-ABL1 negative HL-60 cells was observed (viability remained ≥95%) upon exposure to ASP210. Conclusions: The present study demonstrates the cytoreductive potential of ASP210 in terms of its ability to induce apoptosis in both BCR-ABL1 dependent and independent TKI-resistant CML cells, with no effect on BCR-ABL1 negative cells.

Real-world data on regimens for relapsed/refractory multiple myeloma (RRMM) are limited. Daratumumab in combination with bortezomib and dexamethasone is a promising new treatment. The aim of this analysis was to assess the outcomes of daratumumab-bortezomib-dexamethasone (DVd) combination for the treatment of patients with RRMM in a real-world setting. All consecutive RRMM patients who received at least two cycles of DVd treatment between December 2016 and July 2020 were identified. We analyzed the clinical characteristics and survival of 47 patients treated at 7 Slovak centers outside of the clinical trials. The median age was 65 years (range, 35 to 83). The median (range) number of lines of therapy per patient was 3 (2-6). All patients were previously exposed to PIs (proteasome inhibitors) and IMIDs (immunomodulatory drugs), the majority of patients (70.2%) had double refractory (IMIDs and PI) disease and 72.3% of patients were refractory to their last therapy. Most patients presented with high-risk characteristics, including 25.6% adverse cytogenetics and 25.5% extramedullary disease. The majority of patients responded with an overall response rate of 78%, we found complete response in 3, very good partial response in 22, partial response in 12, minor response or stable disease in 9, and progressive disease in 1 patient. After a median follow-up period of 8 months, the median progression-free survival was 10 months. There was a longer progression-free survival in those with 2 vs. >2 prior treatments, with equally good effectivity in standard-risk and high-risk cytogenetic groups. The adverse events were usually mild, none leading to permanent drug interruptions. Daratumumab-bortezomib-based combinations are efficacious and safe regimens in RRMM patients in the real-world setting. This is the first analysis in Slovakia addressing the DVd combination outside of the clinical trial setting.

Introduction: Clinical trials have demonstrated the effectiveness of the CD30-targeted antibody-drug conjugate brentuximab vedotin (BV) for the treatment of relapsed/refractory Hodgkin lymphoma (R/R HL). In this study, we report on outcomes with BV in a real-world setting using data collected in clinics in the Czech Republic and Slovakia. Patients and Methods: Clinical and epidemiological data for patients with R/R HL who received treatment with BV at eight centers across the Czech Republic and Slovakia were examined. Data were amalgamated and analyzed retrospectively. Results: Clinical data for 58 patients (median age: 30.5 years) with R/R HL who received BV during the course of their treatment were collected and analyzed. Patients had received a median of 3 prior treatment regimens and most (91%) were treated with BV after relapse following autologous stem cell transplantation. Therapeutic responses after BV included 19 (33%) complete responses (CRs) and 8 (14%) partial responses. CRs occurred more frequently in patients who had received fewer prior treatment regimens. The 1-, 2-, and 3-year overall survival (OS) rates from initiation of BV were 78%, 62%, and 41%, respectively. Conclusion: Response rates and OS in this analysis of BV in real-world settings in the Czech Republic and Slovakia were consistent with those reported for pivotal clinical trials and from previous studies outside the clinical trial setting. The results support the efficacy of BV for treatment of R/R HL in real-life clinical practice.

Purpose: While patients with early-stage Hodgkin lymphoma (HL) have an excellent outcome with combined treatment, the radiation therapy (RT) dose and treatment with chemotherapy alone remain questionable. This noninferiority trial evaluates the feasibility of reducing the dose or omitting RT after chemotherapy. Methods and Materials: Patients with untreated supradiaphragmatic HL without risk factors (age >= 50 years, 4 to 5 nodal areas involved, mediastinum-thoracic ratio >= 0.35, and erythrocyte sedimentation rate >= 50 mm in first hour without B symptoms or erythrocyte sedimentation rate >= 30 mm in first hour with B symptoms) were eligible for the trial. Patients in complete remission after chemotherapy were randomized to no RT, low-dose RT (20 Gy in 10 fractions), or standard-dose involved-field RT (36 Gy in 18 fractions). The limit of noninferiority was 10% for the difference between 5-year relapse-free survival (RFS) estimates. From September 1998 to May 2004, 783 patients received 6 cycles of epirubicin, bleomycin, vinblastine, and prednisone; 592 achieved complete remission or unconfirmed complete remission, of whom 578 were randomized to receive 36 Gy (n=239), 20 Gy of involved-field RT (n=209), or no RT (n=130). Results: Randomization to the no-RTarm was prematurely stopped (>= 20% rate of inacceptable events: toxicity, treatment modification, early relapse, or death). Results in the 20-Gy arm (5-year RFS, 84.2%) were not inferior to those in the 36-Gy arm (5-year RFS, 88.6%) (difference, 4.4%; 90% confidence interval [CI] -1.2% to 9.9%). A difference of 16.5% (90% CI 8.0%-25.0%) in 5-year RFS estimates was observed between the no-RT arm (69.8%) and the 36-Gy arm (86.3%); the hazard ratio was 2.55 (95% CI 1.44-4.53; P<.001). The 5-year overall survival estimates ranged from 97% to 99%. Conclusions: In adult patients with early-stage HL without risk factors in complete remission after epirubicin, bleomycin, vinblastine, and prednisone chemotherapy, the RT dose may be limited to 20 Gy without compromising disease control. Omitting RT in these patients may jeopardize the treatment outcome. (C) 2017 Elsevier Inc. All rights reserved.

Purpose: For early-stage Hodgkin lymphoma (HL), optimal chemotherapy regimen and the number of cycles to be delivered remain to settle down. The H9-U trial compared three modalities of chemotherapy followed by involved-field radiotherapy (IFRT) in patients with stage I-II HL and risk factors (NCT00005584).Patients and methods: Patients aged 15-70 years with untreated supradiaphragmatic HL with at least one risk factor (age >= 50, involvement of 4-5 nodal areas, mediastinum/thoracic ratio >= 0.35, erythrocyte sedimentation rate (ESR) >= 50 without B-symptoms or ESR >= 30 and B-symptoms) were eligible for the randomised, open label, multicentre, non-inferiority H9-U trial. The limit of non-inferiority was set at 10% for the difference between 5-year event-free survival (EFS) estimates. From October 1998 to September 2002, 808 patients were randomised to receive either the control arm 6-ABVD-IFRT (n = 276), or one of the two experimental arms: 4-ABVD-IFRT (n = 277) or 4-BEACOPPbaseline-IFRT (n = 255).Results: Results in the 4-ABVD-IFRT (5-year EFS, 85.9%) and the 4-BEACOPPbaseline-IFRT (5-year EFS, 88.8%) were not inferior to 6-ABVD-IFRT (5-year EFS, 89.9%): difference of 4.0% (90% CI, -0.7%-8.8%) and of 1.1% (90% CI,-3.5%-5.6%) respectively. The 5-year overall survival estimates were 94%, 93%, and 93%, respectively. Patients treated with combined modality treatment chemotherapeutic regimen comprising doxorubicin (Adriamycin), bleomycin, vincristine (Oncovin), cyclophosphamide, procarbazine, etoposide and prednisone (BEACOPP) baseline more often developed serious adverse events requiring supportive measures and hospitalisation compared with patients receiving the chemotherapeutic regimen comprising doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD).Conclusions: The trial demonstrates that 4-ABVD followed by IFRT yields high disease control in patients with early-stage HL and risk factors responding to chemotherapy. Although non-inferior in terms of efficacy, four cycles of BEACOPP(baseline) were more toxic than four or six cycles of ABVD. (C) 2017 Elsevier Ltd. All rights reserved.

The objective of this cross-sectional survey was to measure the resource utilisation and costs associated with health-care management of patients with aggressive histological types of Non-hodgkin lymphomas (a-NHLs) in Slovakia and to provide a basis for cost-effectiveness evaluations. The latest official national data on epidemiology of all NHLs are available for year 2008, prediction to 2015 indicates the age-standardized (ASR-W) incidence to be 4.9/100,000 (n=446 cases), from that DLBCL is estimated to be 311 cases (3.1/100,000). Overall point prevalence of all NHLs is estimated to 1,404 patients. Descriptive data of 1,080 a-NHLs patients from 3 biggest NHLs-centers from whole Slovakia were collected and analyzed. All types of health-care services, treatment management and costs were analyzed. Continuous variables were calculated using standard descriptive statistics methods. 98.97% of patients were treated by the 1st line (L), out of them 97.10% of patients (95%CI:97.01%-97.19%) by rituximab. Proportion of remissions after 1stL represented 63.47%, deaths 6.76% and progression/relaps 29.77% (95%CI:29,18%-30,36%), out of them 91.99% (95%CI:91.49%-92.50%) received 2ndL therapy. Proportion of remissions after 2ndL was 26.48%, deaths 11.27% and progression/relaps 62.25% (95%CI:62.16%-62.34%), out of them 91.04% (95%CI:90.42%-91.66%) received 3rdL treatment. Proportion of remissions after 3rdL represented 7.86%, deaths 35.68%, progression/relaps 57.61% (95%CI:56.99%-58.23%), out of them 20.45% of patients (95%CI:18.50%-22.41%) are re-treated with rituximab. Overall costs of patient on active treatment during therapy represented €1,609.80/28 days (95%CI: €1,571.39-€1,648.72), in the post-treatment time €31.56 (95%CI:€29.16-€34.10). Costs of palliative care represented €1,283.53/28 days (95%CI:€1,197.88-€1,372.94) and one-off costs €405.56 (95%CI:€400.88-€410.26). Costs of adverse events management ranged in the grade 2 from €10.58/pain (95%CI:€8.50-€11.06) to €103.23/fatigue (95%CI:€100.01-€106.49); in the grade 3/4 from €111.75/lymphopenia (95%CI:€105.78-€117.73) to €4,518.06/other malignant tumors (95%CI:€4,476.87-€4,559.26). Results of this cross-sectional survey determined the treatment strategies and average direct cost per a-NHL patient and can be used for the purposes of pharmaco-economic evaluations.

Previous randomized trials have demonstrated that rituximab maintenance (R-maintenance) can prolong time to progressive disease in patients with follicular lymphoma (FL). The phase IIIb MAXIMA study (NCT00430352) was a large prospective evaluation of R-maintenance in a daily care setting. The primary objective was safety. Secondary objectives included progression-free survival, overall survival, time to next lymphoma treatment, and partial response (PR) to complete response/unconfirmed (CR/CRu) conversion rate. Patients (n = 545) with first-line or relapsed FL who responded to 8 cycles of rituximab-based induction received R-maintenance every 2 months for 2 years. At study entry, 380 patients had CR or CRu, and 165 had PR. The median age was 57.0 years. The most common non-hematologic adverse events (AEs, excluding infusion-related reactions) were cough (9.9 % of patients), fatigue (7.5 %), nasopharyngitis (7.1 %), back pain (6.5 %), diarrhea (6.9 %), arthralgia (6.0 %), headache and hypertension (5.2 % each), and pyrexia (5.1 %). The majority of AEs were grade 1 or 2. Grade 3, 4, and 5 infections occurred in 21 (3.9 %), 2 (0.4 %), and 1 (0.2 %) patient, respectively. Fifty-one hematologic AEs occurred in 6.6 % (n = 35) of patients. Grade 3/4 prolonged neutropenia and hypogammaglobulinemia occurred in 13 (2.4 %) and 5 (0.9 %) patients, respectively. All cases of prolonged neutropenia or hypogammaglobulinemia were manageable and resolved. Fast infusion did not alter the safety profile. Efficacy was comparable with results from previous trials. R-maintenance is safe in a daily care setting for patients with first-line or relapsed FL.