During the pre-Omicron phases of the COVID-19 pandemic, patients with hematological neoplasms were characterized by very high morbidity and mortality rates. Remdesivir, a viral RNA-polymerase inhibitor, interferes with key SARS-CoV-2 enzymes, preventing the virus from multiplying. The use of convalescent plasma (CP) in treating patients with COVID-19 has been shown to be beneficial in patients with an impaired humoral response to infection, including most of those on active treatment for hematologic malignancies. This retrospective, non-interventional study was performed using the Croatian Cooperative Group for Hematological Diseases database of patients with hematological malignancies infected with SARS-CoV-2. Patients treated with remdesivir and/or CP were matched to those untreated according to age, disease type, and antineoplastic therapy. We identified 119 patients treated with remdesivir and/or CP fulfilling entry criteria and matched 116 according to our established criteria to one of the 374 untreated patients. Treatment significantly reduced COVID-19 mortality. The beneficial effect of antiviral therapy was limited to those who started antiviral treatment within 7 days of the onset of symptoms. Due to the exclusive enrolment of hematological patients with COVID-19, our study provides unique insights into the benefits of early application of both antiviral and CP therapy. It emphasizes the need for early administration before the infection has transformed into the hyperinflammatory phase.

BackgroundIbrutinib is effective for B-cell malignancies but is associated with cardiovascular adverse events, including atrial fibrillation (AF) and hypertension. Longitudinal data on left atrial (LA) remodeling during treatment are limited. We characterized serial changes in LA size and function during chronic ibrutinib therapy.MethodsIn this prospective observational cohort, 40 patients starting ibrutinib underwent clinical assessment, 24–72-hour Holter monitoring, and echocardiography with LA strain at baseline and 3, 6, 12, and long-term (nominal 36-month) follow-up. Primary analyses used observed paired data, random-intercept mixed models, standardized response means (SRMs), and Benjamini-Hochberg adjustment across 24 primary contrasts.ResultsMedian age was 65 years and 53% were female. Paired mean LAVI changes were +1.52 mL/m² at 3 months (n = 38), +1.68 at 6 months (n = 36), +2.62 at 12 months (n = 33), and +2.15 at long-term follow-up (n = 31; all q ≤ 0.020). LA reservoir strain worsened from 6 months onward (all q ≤ 0.031), while LA contractile strain, LA lateral-wall TDI, and LV GLS worsened at every follow-up (all q ≤ 0.009). Results were materially unchanged after adjustment for time-varying hypertension and in complete-case sensitivity analyses. Incident AF occurred in 5/40 patients (12.5%; 95% CI 5.5%–26.1%).ConclusionDuring chronic ibrutinib therapy, longitudinal imaging showed modest LA enlargement and consistent deterioration in several LA deformation indices. These treatment-associated observations require confirmation in controlled cohorts.Clinical trial registrationClinicalTrials.gov, identifier NCT03751410.

Multiple myeloma (MM) is a clonal hematologic malignancy characterized by plasma cell proliferation in the bone marrow. One of the most common clinical presentations is skeletal-related events (SREs), characterized by osteolysis of the bone, leading to a significant morbidity and mortality. The main aim of this review article is to provide an overview of the pathogenesis and evidence-based, guideline-recommended treatment of SREs. MM bone homeostasis is altered by numerous pathways and cytokines, leading to the pathogenesis of bone and osteolytic lesions. Historically, bisphosphonates were the mainstay of treatment, but due to toxicities and contraindications in renal impairment, denosumab—a monoclonal antibody targeting the RANKL-RANK axis, given once per month—may have become the treatment of choice, especially with three biosimilars being approved, yet adverse events may be troublesome. Furthermore, it seems that anti-MM-directed therapy has an impact on bone turnover, yet the results are premature. However, despite basic research unraveling novel targets such as micro ribonucleic acids, translational research and randomized clinical trials are lagging behind, making this area an unmet need—despite the fact that precision, risk-adapted, biomarker- and imaging-driven medicine should be a valid clinical goal in this setting.

BACKGROUND:Carfilzomib-based regimens brought a significant improvement in the treatment of relapsed/refractory multiple myeloma (RRMM). Even though efficacy and safety profiles of carfilzomib are well-established in several clinical trials, there is limited real-world data with carfilzomib-based protocols. Here we present our real-world experience with carfilzomib-based regimens for treatment of patients with RRMM in Croatia. METHODS:Data on patients with RRMM starting carfilzomib-based protocols in the period between June 2019 and February 2023 was collected by retrospective chart review from 14 Croatian centres. RESULTS:A total of 119 patients with RRMM were included; median age was 66 years (range 45-83 years), 59 (49.6 %) were females, and the median number of previous lines of therapies was 2 (range 1-8). Triplet based regimen was treatment choice in 84 (70.6 %) and 35 (29.4 %) patients were treated with carfilzomib in combination with dexamethasone (Kd). Overall response rate was 61.7 %, with 20 patients (18.7 %) achieving complete response (CR). Median progression free survival (PFS) and overall survival (OS) for entire cohort were 9.4 and 13.2 months, respectively. Median PFS was 12.8 months and 4.1 months for the triplets and doublets, respectively; the corresponding median OS was 18.6 and 7.9 months, respectively. The most common adverse events were anemia and thrombocytopenia; 19 patients (16 %) experienced cardiovascular events. CONCLUSION:This is the first study to analyze clinical outcomes of RRMM patients treated with carfilzomib-based regimens in Croatia. Carfilzomib-based regimens showed substantial efficacy and acceptable toxicity in RRMM, especially in earlier treatment lines and triplet combinations.

Multiple myeloma (MM) is a hematologic disease characterized by the clonal expansion of malignant plasma cells that accumulate in the bone marrow, leading to osteolytic bone disease, hypercalcemia, anemia, and renal dysfunction. Daratumumab was the first monoclonal anti-CD38 antibody approved for the treatment of MM, initially in relapse/refractory settings and, more recently, for newly diagnosed patients. Increased first-line usage of daratumumab will also substantially change treatment approaches for patients with relapsed/refractory disease. Due to the cost and availability of bispecific T cell redirecting antibodies (BsAbs) and chimeric antigen receptor T cell therapy (CAR-T) in real-life settings in many countries, retreatment with daratumumab in subsequent lines of therapy might be a reasonable choice. Data regarding efficacy and optimal combinations of daratumumab retreatment are lacking, and here we provide a short literature review of available data. We identified only a small number of articles based on retrospective analysis of medical records in real-life settings. A strong consistency in results regarding response rates and treatment duration was noticed among mainly heavily pre-treated MM patients, with approximately half of patients achieving at least partial remission (PR) after retreatment with daratumumab-based protocol. The duration of treatment and time to the next treatment for retreatment episodes were considerable and consistent with clinical expectations for later lines of therapy. The analysis of data in this literature review indicates that daratumumab retreatment may provide meaningful clinical benefit to some patients with relapsed/refractory MM despite having prior exposure. However, further research is needed to identify clinical and biological parameters that may predict favorable responses to daratumumab retreatment.

Background:The coronavirus disease 2019 (COVID-19) patients with hypogammaglobulinemia who are sick enough to require intensive care unit (ICU) admission exhibit high mortality rates. This study investigates whether the use of rescue hemoadsorption is associated with increased survival and/or improved clinical and biological parameters.Methods:In this prospective study, critically ill COVID-19 patients were consecutively enrolled, and serum protein electrophoresis was used to screen for hypogammaglobulinemia (defined as a gamma-globulin fraction below the 10th percentile and confirmed by a serum IgG level below 700 mg/dL). Twelve patients received hemoadsorption for immunomodulation. The same laboratory parameters were collected from 24 propensity-matched control patients who did not receive hemoadsorption.Results:There was no significant survival difference between patients treated with hemoadsorption and control patients. There was also no significant post-treatment improvement in the clinical parameters or sequential organ failure assessment (SOFA) scores for patients who received hemoadsorption compared to those who did not. Notably, 90% of all patients (32/36) died before day 28, regardless of whether they received hemoadsorption. An independent association between hypogammaglobulinemia and death within 28 days was found for all patients: Hazard ratio (HR) 0.32 (0.15, 0.66), P < 0.001.Conclusion:Hemoadsorption was not associated with increased survival in COVID-19 ICU patients with hypogammaglobulinemia. Our study highlights that a diagnosis of impaired humoral immunity could be a useful clinical predictor of high mortality and of non-response to hemoadsorption for patients with severe COVID-19.

ABSTRACT:Genetic abnormalities in multiple myeloma (MM) influence treatment outcomes and may inform therapeutic decisions. The most common chromosomal translocation in MM is t(11;14); however, its role in disease progression is not well defined. We report results from MEDICI, a global, minimally invasive, prospective study evaluating t(11;14) status in newly diagnosed MM (NDMM) and relapsed/refractory MM (RRMM). MEDICI enrolled adult patients (≥18 years) with MM with bone marrow (BM) aspirates collected at diagnosis and/or disease relapse. The primary objective was to determine t(11;14) prevalence in patient BM samples using fluorescent in situ hybridization (FISH) with plasma cell enrichment. Samples from 525 patients (NDMM, n = 306; RRMM, n = 219) were analyzed for t(11;14), with 498 patients (95%) having successful BM FISH test. Prevalence of t(11;14) was 22.1% (110/498 patients; 95% confidence interval [CI], 18.5-26.0) in the overall patient population, 18.8% (56/298 patients; 95% CI, 14.5-23.7) in NDMM, and 27.0% (54/200 patients; 95% CI, 21.0-33.7) in RRMM. Patients with t(11;14)-positive MM were evenly distributed across disease stages (stage I, 24.1%; stage II, 20%; stage III, 21.3%); however, higher rates were observed in African American patients (RRMM odds ratio [OR], 7.27, 95% CI, 1.33-39.83; P = .022) and light-chain only disease (NDMM OR, 3.02, 95% CI, 1.33-6.87; P = .008). Chromosome 1q abnormalities occurred more often in the absence of t(11;14); however, higher frequency of mutation in the plasma cell differentiation regulator IRF4 was detected in t(11;14) presence. In conclusion, the results from MEDICI demonstrated reproducible t(11;14) detection with a real-world prevalence of 22.1% in MM. This trial was registered at www.ClinicalTrials.gov as #NCT04721002.

Background/Objectives: Ibrutinib has revolutionized the treatment of chronic lymphocytic leukemia but has off-target side effects, most notably cardiac. In order to evaluate the efficacy and toxicity of ibrutinib treatment, risk factors for adverse outcomes and the influence of pretreatment cardiologic evaluation, KroHem collected data on Croatian patients with chronic lymphocytic leukemia treated with this drug. Methods: This is a retrospective survey performed in order to analyze the efficacy and toxicity of ibrutinib in a real-life setting. Patients starting therapy with ibrutinib for chronic lymphocytic leukemia between the time the drug became reimbursable in 2015 and 31 December 2021 were included, irrespective of treatment line. Results: We identified 436 patients fulfilling entry criteria; 404 (92.7%) responded to treatment. Cardiovascular side effects occurred in 25.0% of patients and hemorrhagic in 15.6%. The dose of ibrutinib was permanently reduced in 22.2% of patients. Median follow-up of the cohort was 29 months (IQR 18-41 months), estimated median overall survival 75 months (IQR 36 months-not reached), progression-free survival 54 months (IQR 24-81 months) and time on ibrutinib treatment 44 months (IQR 14-78 months). Factors significantly related to overall survival in multivariate analysis were stage, treatment line and age. Factors significantly related to progression-free survival in multivariate analysis were treatment line, age and pretreatment history or ECG finding of cardiac arrhythmia. Factors significantly related to time on ibrutinib treatment in multivariate analysis were age, pretreatment history or ECG finding of cardiac arrhythmia, and permanent dose reduction for toxicity. Sex, FISH and the presence of arterial hypertension were not independently significantly related to any of these outcomes. Pretreatment cardiologic consultation did not improve time on ibrutinib therapy, progression-free survival, overall survival, risk of stopping treatment due to cardiovascular side effects or risk of cardiovascular or sudden death, neither in the whole cohort nor in the subgroup of patients with and without pretreatment cardiac arrhythmia. Conclusions: Our analysis confirms the efficacy and tolerability of ibrutinib for the treatment of chronic lymphocytic leukemia. Patients older than 75 do significantly less well. Routine pretreatment cardiologic consultation does not improve outcomes and should not be considered part of standard pretreatment assessment without additional proof of its usefulness. Future investigations should aim at identifying predictive factors, mechanisms, and preventive strategies for reducing cardiotoxicity in chronic lymphocytic leukemia patients taking Bruton tyrosine kinase inhibitors.

Background and Objectives: Ixazomib, used in combination with lenalidomide and dexamethasone (IRd), has shown efficacy in clinical trials for relapsed/refractory multiple myeloma (RRMM). Materials and Methods: This study evaluates the real-world effectiveness and safety of IRd in Croatian RRMM patients. A retrospective analysis was conducted on 164 RRMM patients treated with ixazomib at nine Croatian haematology centres from November 2016 to February 2023. Data on patient demographics, treatment regimens, and outcomes were collected and analysed using Kaplan–Meier survival curves and Cox proportional hazards models in R. The median age at ixazomib initiation was 66 years (range 40–91). Results: The overall response rate (ORR) was 65.8%, with 42% of patients achieving a very good partial response (VGPR) or better. The median progression-free survival (PFS) was 15.4 months, while median overall survival (OS) was 28.2 months. Hematologic toxicities included anaemia (53%), neutropenia (50%), and thrombocytopenia (45%). Infective complications, primarily COVID-19 and pneumonia, were reported in 38% of patients. The safety profile was consistent with previous studies, indicating manageable adverse events. Ixazomib-based therapy is effective and well tolerated in a real-world Croatian RRMM population. Conclusions: The findings align with clinical trial results, demonstrating the applicability of ixazomib in routine clinical practice. Further studies are needed to optimise treatment sequencing and improve patient outcomes.

Background/Objectives: Obinutuzumab was approved for front-line treatment of chronic lymphocytic leukemia in combination with chlorambucil pulses administered every 2 wks. Alternative schedules of chlorambucil enable the administration of higher total chlorambucil doses, and have better antileukemia activity. So far, evidence on the feasibility of combining obinutuzumab with alternative chlorambucil schedules is lacking. We performed this retrospective analysis to analyze real life outcomes in chronic lymphocytic leukemia patients receiving a combination of obinutuzumab with different chlorambucil schedules. Methods: This was a retrospective survey performed in order to analyze the feasibility and efficacy of different obinutuzumab and chlorambucil combinations in a real-life setting. Patients receiving this combination as a front-line therapy for chronic lymphocytic leukemia in participating centers, outside of clinical trials, in 2017 and 2018 were included. Results: Seventy-three patients fulfilling entry criteria were identified. Their median age was 76 years, and ranged from 58 to 90 years. The median follow up time was 59 months. The response rate was 89%, with a median progression-free survival time of 27 months, and an overall survival time of 49 months. Chlorambucil was administered as planned in 15 of the 22 (79%) patients treated with chlorambucil pulses every 2 weeks; in 15 of the 42 (34%) patients treated with 7-day courses of chlorambucil administered every 4 weeks; and in 0 of the 10 patients treated with a continuous high dose of chlorambucil (p = 0.002). Changes in treatment schedules were made due to side effects. The progression-free and overall survival rates were similar between the three groups. Conclusions: The combinations of obinutuzumab with more intensive chlorambucil schedules are less feasible, preventing the administration of the intended higher total dose of chlorambucil, and do not improve outcomes in comparison to chlorambucil pulses administered every 2 weeks.

Background: Most Hodgkin lymphoma (HL) patients younger than 60 years are nowadays cured, especially those treated with front-line escalated BEACOPP (escBEACOPP), thus understanding long-term side effects is essential. Avascular joint necrosis (AVN) is a known side-effect of this regimen, possibly related to bone mineral density (BMD) loss. In order to reduce steroid-related side-effects, we reduced steroid exposure from the original 14 days to 7-8 days per escBEACOPP cycle without loss of efficacy and a trend towards reduced osteoarticular side effects. This study was performed to further investigate the impact of escBEACOPP and different steroid schedules on bone metabolism in patients with classical HL. Methods: Previously untreated patients with classical HL receiving at least two cycles of escBEACOPP for early unfavorable (EU, stage I - II with at least one unfavorable prognostic factor as per GHSG criteria) or advanced stage disease (AS, stage IIB bulky - IV), and at least one evaluable PET-CT for BMD assessment were included. BMD was assessed using the Hounsfield unit (HU) scale on axial images of the L3 vertebra from PET-CT scans performed at baseline, post-treatment, or during follow-up when available. The threshold for normal BMD was set at 160 HU, with values between 100-159 HU considered osteopenia and below 100 HU as osteoporosis. BMD reduction of ≥15% and ≥25% from baseline to post-treatment were considered clinically relevant. Demographic, treatment, steroid administration, and side-effects data were obtained retrospectively from patient medical records. Data were analyzed using descriptive statistics, chi-square tests, Fisher's exact tests, repeated measures ANOVA, t-tests, and logistic regression analysis. Results: The study cohort consisted of 177 patients (56.5% male, median age 31 years, all Caucasian). Seventy-four % had AS disease, of which 61% were stage IV. Sixty-two % received 6 cycles of escBEACOPP, 22% received 2 cycles of escBEACOPP + 2 cycles of ABVD, and 16% other combinations. BMD changed significantly across all time points (p<0.001). Baseline mean BMD was 204.71 (SD = 44.4), decreasing to 161.49 (SD = 43.84) post-treatment and 170.77 (SD = 49.45) at follow-up. Baseline BMD measurements showed normal BMD in 84.8% of patients, 13.6% had osteopenia, and 1.7% had osteoporosis. Post-treatment, the proportions were 50.6% normal, 42.9% osteopenia, and 6.5% osteoporosis. The median BMD reduction from baseline to post-treatment for 117 evaluable patients was 23%, with 64% of patients having a BMD reduction ≥15% and 45% ≥25%. During follow-up, the median BMD reduction from baseline for 44 evaluable patients was 18%, with 54% of patients having a reduction ≥15% and 22% ≥25%. Age (stratified by groups <30, 31-40, 41-50, 50+y) significantly influenced the risk of having osteopenia at baseline (OR 4.79, p<0.001). Age was also significantly associated with the risk of developing osteoporosis after treatment (p<0.001, OR 5.85). Stage IV disease was a significant predictor of BMD reduction of ≥15% (p = 0.01), whereas age, gender, baseline BMD, EU vs. AS, and number of BEACOPP cycles were not. Only age presented an increased risk of a more significant BMD decline by ≥25% (p=0.014, OR 1.85). The decrease in steroid dosing from 14 to 7-8 days of prednisone per cycle did not significantly impact BMD outcomes (p=0.404 for reduction≥15%; p=0.51 for ≥25%). There was no correlation between BMD dynamics and the development of clinically relevant osteoarticular events (13 pts, 7.23%). No pathological fractures were documented. Conclusions: This study highlights a significant reduction in BMD in HL patients treated with escBEACOPP, with only minor recovery during follow-up. Despite efforts to reduce steroid-related bone loss by decreasing steroid exposure, no significant improvements were observed. The BMD reduction was more pronounced in older patients and in patients with stage IV disease, regardless of number of escBEACOPP cycles, suggesting that certain host and disease characteristics likely contribute to BMD loss in addition to therapy. Using routine PET-CT scans for BMD measurement in HU is feasible and easy to implement in everyday clinical practice. Abnormal results should trigger further work-up and DEXA confirmation. Long-term monitoring and intervention strategies, as well as development of less toxic regimens, are crucial for managing bone health in HL patients.

Patients with mantle cell lymphoma (MCL) who experience first relapse/refractoriness can be categorized into early or late progression-of-disease (POD) groups, with a threshold of 24 months from the initial MCL diagnosis. Bruton tyrosine kinase inhibitors (BTKi) are established standard treatment at first relapse, but their effectiveness as compared to chemoimmunotherapy (CIT) in late-POD patients remains unknown. In this international, observational cohort study, we evaluated outcomes amongst patients at first, late-POD beyond 24 months. Patients treated upfront with BTKi were excluded. The primary objective was progression-free survival from time of second-line therapy (PFS-2) of BTKi versus CIT. After accrual, all patients were prospectively followed-up. Overall, 385 late-POD patients were included from 10 countries. Their median age was 59 (range:19-70) years and 77% were males. Median follow-up from time of first relapse was 53 months (range:12-144). Overall, 114 patients had second-line BTKi, while 271 had CIT, consisting of rituximab-bendamustine (R-B, n=101), R-B and cytarabine (R-BAC, n=70), or other regimens (mostly cyclophosphamide-hydroxydaunorubicin-vincristine-prednisone-CHOP- or platinum-based, n=100). The two groups were balanced for clinicopathological features, and median time to first relapse (48 months for both). Overall, BTKi was associated with significantly prolonged median PFS-2 than CIT [not reached-NR vs 26 months, respectively, P=.0003], and overall survival [NR and 56 months, respectively, P=.03]. Multivariate analyses showed that BTKi was associated with lower risk of death than R-B and other regimens (hazard ratio-HR, 0.41 for R-B, 0.46 for others), but similar to R-BAC. These results may establish BTKi as the preferable second-line approach in BTKi-naïve MCL patients.

Introduction: Multiple myeloma (MM) is the second most common hematologic malignancy characterized by bone marrow infiltration by monoclonal plasma cells (PC). Several well-defined genetic abnormalities have been identified as relevant with the disease. Although novel therapies have improved overall survival most patients with MM will eventually relapse or become refractory (RR). Therefore, there is an emerging need for better therapeutic regimens including personalized medicine based on specific biomarkers. Venetoclax (Ven) is a selective and potent oral B-cell lymphoma-2 (BCL-2) inhibitor that has shown significant antimyeloma activity in patients with t(11;14) RRMM (Kumar et al. Blood 2017; 130 (22): 2401-2409). In the phase 3 BELLINI (NCT02755597) study, patients with t(11;14) RRMM showed improved response rates and progression-free survival when treated with Ven in combination with bortezomib and dexamethasone compared to placebo-bortezomib-dexamethasone (Kumar et al. Lancet Oncol. 2020; 21:1630-1642). These results suggest that t(11;14)-based selection of patients with MM may represent a potential biomarker for venetoclax-based treatment regimens. An ongoing phase 3 study, CANOVA (NCT03539744), is evaluating the combination of Ven and dexamethasone in patients with t(11;14) RRMM compared to standard of care pomalidomide-dexamethasone (Mateos et al. J Clin Oncol 2020; 38: no. 15_suppl) . Understanding the prevalence of t(11;14) MM in a real-world setting will provide important insights for targeted therapy in this patient subpopulation. Therefore, the MEDICI study was designed to evaluate the real-world prevalence of t(11;14) as detected by interphase fluorescence in situ hybridization (FISH) technology in patients with MM. Methods: MEDICI (NCT04721002) is an ongoing, prospective, multicenter minimally interventional study. The primary objective is to determine the prevalence of t(11;14) in both newly diagnosed (ND) and RRMM as determined by interphase FISH analysis of monoclonal bone marrow (BM) PCs. All patients (≥18 years) included in the study signed informed consent. BM aspirates (BMA) were collected as part of standard of care procedures performed at diagnosis and disease relapse. Patients with no BMA sample at the time of diagnosis or confirmation of relapse were excluded from the trial. The primary endpoint was the t(11;14) status of the earliest bone marrow sample collected at initial diagnosis or across subsequent lines of therapies. CD138-enriched BMA samples were evaluated for t(11;14) by FISH (Abbott Molecular). Results: Sixty-two patients were included at the time of the interim analysis (data cut-off 09 March 2022). Median age was 67.5 years, 51.6% were male and 95.2% were Caucasian. Patients with ECOG performance status ≤2/>2/unknown was 83.9%/8.1%/8.1%. ISS stage across patients were stage I (30.6%), stage II (22.6%), stage III (33.9%) and unknown (12.9%) respectively. Del 17p was observed in 6.5% of patients and gain of chromosome 1q in 25.8% of patients. There were 36 and 26 patients with NDMM and RRMM respectively. One patient had longitudinal samples. The overall prevalence of patients with t(11;14) MM was 30.0%, which was similar between NDMM (25.0%) and RRMM (37.5%) patients (Table). The distribution of patients across the observed t(11;14) FISH fusion (F) categories (1F/2F/≥3F) for NDMM was 33.3%/22.2%/22.2% and 44.4%/55.6%/0.0% in RRMM pts (Table). Across lines (L) of therapy, the distribution of t(11;14)+ patients were similar between 1L (25.0%) , 2L (35.7%), and 3L+ (36.4%) (Table). The distribution of t(11;14)+ patients across disease stage was also similar between stage I (31.6%), stage II (28.6%), and stage III (25.0%) respectively. There were 8 patients with unknown stage of disease, 3 among them were t(11;14)+. Conclusion: Interim analysis of MEDICI demonstrated that prevalence of t(11;14) was consistent across ND and RRMM setting and independent of line of therapy and disease stage. This study is currently ongoing, and further updates will be provided upon presentation. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Background and Objectives: eBEACOPP is the most effective chemotherapy regimen for younger patients with early unfavorable (EU) and advanced-stage (AS) Hodgkin lymphoma (HL), albeit with significant toxicities. The 14-day/cycle prednisone course contributes to side effects, including osteoarticular events like avascular bone necrosis (AVN). Our center has been using eBEACOPP since 2009 for AS and 2014 for EU patients. In 2016, we reduced prednisone treatment to 7–10 days to lessen AVN risk. We analyzed the effects of this approach. Materials and Methods: We retrospectively collected data on patients who received at least two cycles of eBEACOPP for first-line HL treatment. Results: A total of 162 patients (33 EU, 129 AS) were included. Their median age was 31 (range 19–59 years), and 88 were males. A total of 94 patients received full corticosteroid courses, and 68 received reduced corticosteroid courses. The overall response rate (ORR) was 98%. Different corticosteroid dosings had no significant effect on ORR, febrile neutropenia episodes, or hospital admissions. After a median follow-up (mFU) of 58 months, the 5yPFS for the entire cohort was 98% vs. 95% for the standard course vs. the short corticosteroids course, respectively (p = 0.37), while the 5yOS was 98% vs. 99% for the standard course vs. short corticosteroids course, respectively (p = 0.87). In AS patients intended to be treated with six eBEACOPP cycles, 5yPFS and 5yOS were 100% vs. 97% and 100% vs. 99% for standard vs. short corticosteroid courses, respectively (p = 0.56 and p = 0.17). In EU patients, 5yPFS was 97% (standard) vs. 95% (short) (p = 0.98) and 5yOS 100% vs. 93.3% (p = 0.87). Osteoarticular events were numerically lower in patients receiving the shorter prednisone course, both in the whole cohort and in the subgroup of patients treated with six cycles of eBEACOPP, but this difference failed to reach statistical significance. Conclusions: eBEACOPP provides excellent and durable first-line disease control. Shortening the corticosteroid course does not compromise efficacy, potentially reducing toxicity. However, longer follow-ups and larger studies are needed for confirmation.

Patients with lymphoid malignancies are at increased risk of death or prolonged infection due to COVID-19. Data on the influence of different antineoplastic treatment modalities on outcomes are conflicting. Anti-CD20 monoclonal antibodies increase the risk of prolonged infection. It is unclear whether this risk is affected by the choice of the antibody (rituximab vs. obinutuzumab). To elucidate the role of antineoplastic therapy on COVID-19 outcomes, KroHem collected data on patients with lymphoid malignancies diagnosed with COVID-19 between October 2020 and April 2021. A total of 314 patients were identified, 75 untreated, 61 off treatment and 178 on treatment. The mortality rate in untreated and off-treatment patients was 15% and 16%; 9% and 10% had prolonged infection. In the on-treatment group, 3% were still prolonged positive at time of data collection, 62% recovered and 35% died; 42% had prolonged infection. Disease type, use of anti-CD20 monoclonal antibodies, prior autologous stem-cell transplantation (ASCT) and line of treatment did not significantly affect mortality. Mortality was higher in older patients (p = 0.0078) and those treated with purine analogues (p = 0.012). Prolonged COVID-19 was significantly more frequent in patients treated with anti-CD20 monoclonal antibodies (p = 0.012), especially obinutuzumab, and purine analogues (p = 0.012). Age, prior ASCT and treatment line did not significantly affect risk of prolonged infection. These data suggest that increased age and use of purine analogues are main risk factors for increased mortality of COVID-19 in patients with lymphoid malignancies. Obinutuzumab further increases the risk of prolonged disease, but not of death, in comparison to rituximab. Epidemiological considerations should be taken into account when choosing the appropriate antineoplastic therapy for patients with lymphoid malignancies.

(1) Background: This study aimed to examine the difference in efficacy and toxicity of involved-field (IFRT) and involved-site radiotherapy (ISRT) fields in infradiaphragmal aggressive non-Hodgkin lymphoma patients. (2) Methods: In total, 140 patients with infradiaphragmal lymphoma treated between 2003 and 2020 were retrospectively evaluated. There were 69 patients (49%) treated with IFRT, and 71 (51%) patients treated with ISRT. The median dose in the IFRT group was 36 Gy, (range 4–50.4 Gy), and in the ISRT group, it was 30 Gy (range 4–48 Gy). (3) Results: The median follow-up in the IFRT group was 133 months (95% CI 109–158), and in the ISRT group, it was 48 months (95% CI 39–57). In the IFRT group, locoregional control was 67%, and in the ISRT group, 73%. The 2- and 5-year overall survival (OS) in the IFRT and ISRT groups were 79% and 69% vs. 80% and 70%, respectively (p = 0.711). The 2- and 5-year event-free survival (EFS) in the IFRT and ISRT groups were 73% and 68% vs. 77% and 70%, respectively (p = 0.575). Acute side effects occurred in 43 (31%) patients, which is more frequent in the IFRT group, 34 (39%) patients, than in the ISRT group, 9 (13%) patients, p > 0.01. Late toxicities occurred more often in the IFRT group of patients, (10/53) 19%, than in the ISRT group of patients, (2/37) 5%, (p = 0.026). (4) Conclusions: By reducing the radiotherapy volume and the doses in the treatment of infradiaphragmatic fields, treatment with significantly fewer acute and long-term side effects is possible. At the same time, efficiency and local disease control are not compromised.

HrvatskaB-stanična kronična limfocitna leukemija (B-KLL) karakterizirana je varijabilnom infiltracijom B-KLL limfocitima različitih limfnih odjeljaka, tj.periferne krvi (PK), koštane srži (KS) i limfnih čvorova (LČ) i limfoidnih organa.Interakcije s različitim mikrookolišima mogu rezultirati različitom aktivnošću bolesti i otpornošću na apoptozu.Novi agensi koji ciljaju Btk i Bcl-2 pokazuju izvanrednu aktivnost u B-CLL.Međutim, oni mogu imati različitu aktivnost u različitim limfnim odjeljcima, dok inhibitori Btk također mogu uzrokovati značajnu redistribuciju B-CLL limfocita između odjeljaka.Cilj ovog istraživanja je procijeniti: 1) postoji li različita ekspresija Bcl-2 obitelji anti-i pro-apoptotskih proteina (Bcl-2, Bax, Bim, mcl-1) i Btk u B-KLL limfocitima iz različitih limfoidnih odjeljaka; 2) odnos promatranih ekspresija prema parametrima bolesti (TTM, TD, stadij, B2MG, LDH); 3) promjene tijekom liječenja Btk inhibitorima.Rezultati: Uključeno je 28 bolesnika s B-KLL (18/10 M/Ž, medijan dobi 71 godina, raspon 48-85) liječenih inhibitorima btk (ibrutinib 24, acalabrutinib 4).Medijan TTM bio je 10,2 (raspon 3,4-23,9), a TD 0,68.Rai stadij III/IV imao je 8 bolesnika.Ekspresija Bcl-2, Mcl-1, Bim, Bax i Btk određena je protočnom citometrijom u CD19+CD5+ limfocitima Ustanovljena je veća ekspresija Bcl-2, Mcl-1 u LN u usporedbi s PK i KS (p<0,05), dok nema promjene u PK praćenju tijekom liječenja ibrutinibom/akalbrutinibom.Nema značajne razlike u ekspresiji Bim između odjeljaka, dok postoji trend veće ekspresije u PB uzorku za praćenje (p=0,054).Nema značajne razlike u ekspresiji Baxa između PB, BM i LN odjeljaka, dok postoji značajan pad ekspresije Baxa u PB uzorku za praćenje tijekom liječenja (p<0,05).p-Btk ima veću ekspresiju u LN u odnosu na PB i BM (p<0,05).Naknadna ekspresija PB p-Btk usporediva je s ekspresijom prije tretmana u PB (unatoč redistribuciji).Nismo pronašli značajnu korelaciju ekspresije obitelji Bcl-2 i ekspresije p-Btk s parametrima tumorske mase i distribucije.Zaključci: postoji različit obrazac ekspresije anti-apoptotskih i pro-apoptotskih članova obitelji