Plerixafor for patients who fail cytokine-or chemotherapy-based stem cell mobilization: Results of a prospective study by the Polish Lymphoma Research Group (PLRG)

Autologous hematopoietic stem cell transplantation (autoHSCT) requires collection of sufficient number of hematopoietic stem cells. The goal of this study was to evaluate efficacy of plerixafor used in patients with lymphoid malignancies failing conventional stem cell mobilization.This was a prospective, non-interventional study. All consecutive patients (n = 109) treated with plerixafor in 11 centers were reported. The drug was used either in case of previous mobilization failure (n = 67) or interventionally, in case of insufficient CD34 cell output during current mobilization (n = 42). Successful mobilization was defined as resulting in collection of ≥ 2 × 10 CD34 cells/kg for single autoHSCT or ≥ 4 × 10 CD34 cells/kg for double procedure.The overall rate of successful mobilization was 55% (55% for single and 56% for double autoHSCT). The median total number of collected CD34 cells/kg was 2.4 (range, 0-11.5) for patients intended for a single transplantation while 4.0 (0.6-16.9) for double procedure. The number of circulating CD34 cells increased after the use of plerixafor regardless of baseline values. The median fold increase was 3.3 (0.3-155). Data from this observational study confirm high efficacy of plerixafor used in routine clinical practice as salvage for patients with lymphoid malignancies failing conventional stem cell mobilization

Analysis of ibrutinib efficacy in a subgroup of chronic lymphocytic leukemia patients with 17p deletion: observational study of the Polish Adult Leukemia Group (PALG)

BackgroundThe 17p deletion is regarded as the strongest poor prognostic factor in chronic lymphocytic leukemia (CLL). Results of recently performed clinical trials have suggested that ibrutinib significantly improves the outcome in this patient group.AimThe study aimed at analyzing the efficacy and adverse events profile of ibrutinib monotherapy in CLL patients with 17p deletion treated in routine clinical practice outside clinical trials.Materials and MethodsClinical response and adverse events profile of ibrutinib monotherapy were assessed in thirty-five CLL patients with 17p deletion treated within the ibrutinib named patients program in Poland.ResultsOverall response rate was 80% (28/35 patients) with median observation time of 24.2 months (range 0,1 – 30,9). Complete remission was observed in 5 patients (14.3%), partial remission in 11 (31.4%), partial remission with lymphocytosis in 13 (37.1%), whereas stable disease and progression was noted in 4 (11.4%) and 1 (2.9%) respectively. Response was not assessed in 1 patient. Median progression-free survival was 29.5 months, whereas median overall survival was not reached. Eleven patients died (7 because of infection, 1 of CLL progression, 1 of sudden cardiac death, 1 of disseminated breast cancer and 1 of unknown causes). In 13 patients (37.1%) at least one 3 or 4 grade adverse event occurred. In 11 patients (31.4%) the treatment was temporary withheld or the dose reduced due to adverse events.ConclusionIbrutinib is characterized by high clinical efficacy and acceptable toxicity in CLL patients with 17p deletion in daily clinical practice

Cardiac complications during DLBCL treatment using R-CHOP

Diffuse large B‐cell lymphoma (DLBCL) is the most frequent of non-Hodgkin’s lymphomas in the world. Immunochemotherapy with rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone (R‐CHOP) is the first-line treatment in this disease. Rituximab is a chimeric murine-human monoclonal anti-CD20 antibody, which binds specifically with CD20 receptor located on majority of mature B-cell lymphocytes. We are presenting the case of sudden cardiac arrest with ventricular fibrillation after intravenous injection of rituximab in a patient with DLBCL type NGC

Echocardiographic Features of Cardiomyopathy in Emery-Dreifuss Muscular Dystrophy

Background. Emery-Dreifuss muscular dystrophy (EDMD) is a very rare type of muscular dystrophy characterized by musculoskeletal abnormalities accompanied by cardiac defects. Two most common genetic subtypes are EDMD1 due to EMD and EDMD2 caused by LMNA gene mutations. The aim of the study was to characterize and compare the cardiac morphology and function in the two main genetic subgroups of EDMD with the use of echocardiography. Methods. 41 patients with EDMD (29 EDMD1 and 12 EDMD2) as well as 25 healthy controls were enrolled in our study. Transthoracic echo with the use of a prescribed protocol was performed. Results. Highly statistically significant differences with regard to left ventricle (LV) volumes between the EDMD and the control group were found. 51% of EDMD patients had an enlarged left atrium and as many as 71% had an enlarged right atrium. The LV ejection fraction (LVEF) was significantly lower in EDMD patients than in the control group which corresponded also with a lower systolic velocity of the mitral annulus. 43% of EDMD patients had LVEF below the normal limit. Diastolic dysfunction was detected in 17% of EDMD patients. There were no significant differences between the two types of EDMD in terms of diameters and volumes of any chamber, as well as the systolic function of both left and right ventricles. Conclusions. A significant number of EDMD patients present LV dilatation and different degrees of systolic dysfunction. Dilatation of the atria dominates over ventricle dilatation. We did not present any significant differences between EDMD1 and EDMD2 in terms of the morphology and the function of the heart

Predictors of mortality and cardiovascular outcomes in Emery-Dreifuss muscular dystrophy in a long-term follow-up

Background: Emery-Dreifuss muscular dystrophy (EDMD) is an extremely rare muscular dystrophy due to either emerinopathy (EMD) or laminopathy (LMNA). The main risk for patients is that of cardiovascular complications.Aims: This study aimed to identify predictors of adverse clinical events in patients with EDMD in a long-term follow-up observation.Methods: A total of 45 patients with confirmed EMD or LMNA mutation were included in the study. The relationships between clinical parameters, the overall survival rate, and risk factors for disease progression were assessed. The primary endpoint was defined as death, while the secondary endpoint comprised death, resuscitated cardiac arrest (RCA), heart transplant (HTX), stroke, end-stage heart failure (ESHF), and hospitalization due to heart failure (HF).Results: During a median length of follow-up observation of ten years (interquartile range, 5–15), ten patients (22%) died, one suffered RCA, two had HTX, and six suffered ischemic strokes (13%). Seven patients developed ESHF, and eight were hospitalized due to HF. The secondary endpoint occurred in 16 patients (36%). LMNA mutation (hazard ratio [HR], 6.01; 95% confidence interval [CI], 1.61–22.4; P = 0.008) and higher serum N-terminal fragment of B-type natriuretic peptide (NT-proBNP) concentration (HR, 1.29; 95% CI, 1.06–1.56 per 100 pg/ml; P = 0.01) increased the risk of death. Higher tricuspid annular plane systolic excursion (TAPSE) decreased the risk for the secondary endpoint (HR, 0.78; 95% CI, 0.68–0.90 mm; P <0.001). NT-proBNP >257 pg/ml and TAPSE <21 mm may be assumed as the best cut-off values for the primary and secondary endpoints, respectively.Conclusions: LMNA mutation and higher NT-proBNP concentration were associated with increased mortality in EDMD. Lower TAPSE was a predictor of a composite secondary endpoint in EDMD

Safety and Efficacy Results from CLI120-001 a Phase 1 Study in RR-AML and HR-MDS: Update from Higher Dose Levels

Background: RVU120, a first-in-class CDK8/19 kinase inhibitor, showed antileukemic activity mediated by inhibition of STAT5 phosphorylation in AML cell lines and patient-derived cells.Clinical activity in a population of patients with relapsed/refractory AML and HR-MDS with poor prognostic factors was shown in a currently ongoing phase 1 dose escalation study (NCT04021368) consistent with the preclinical evidence of both cytotoxic and erythroid and myeloid differentiation effects in cell and mouse models. Aims: The primary objective of the study is to determine the safety profile and the recommended phase 2 dose (RP2D) of RVU120 as a single agent in R/R AML and HR-MDS. Secondary objectives include the characterization of PK, antitumor activity, and exploratory pharmacodynamic (PD) effects. Methods: CLI120-001 is an open-label, multi-center, dose escalation study. RVU120 is administered orally every other day, for a total of 7 doses, in a 3-week treatment cycle until disease progression or unacceptable toxicity. Adverse events are graded according to NCI-CTCAE v.5.0. DLTs are assessed at the completion of Cycle 1. Disease evaluation is performed according to Dohner 2017 and Cheson 2006 response criteria for AML and MDS respectively. Pharmacodynamic assessments (PD) include a flow cytometry assay to assess target engagement by evaluating changes in phosphorylated STAT5. Results: As of 26 Jul 2023, 31 patients received RVU120 at doses between 10 and 175 mg, median age 71 years, median of 3 prior lines of therapy. ECOG PS was 2 in 8 pts, 1 in 20 pts, and 0 in 3pts. No severe drug reactions, no DLT have been reported, with manageable nausea and vomiting being the most frequent treatment-emergent adverse events. Twelve out of the 24 evaluable patients showed clinically relevant benefit. Four patients achieved a reduction of blasts to 18 months with nearly normal Hgb and Plts values. 2 patients with AML-MRC, with baseline RBC and Plt transfusion dependance (TD), became TI and reached normal Plts values. 1 patient with AML-MRC with RBC and Plt TD and severe neutropenia showed RBC and Plt TI and ANC recovery and is currently in C7 of treatment. A correlation between pSTAT5 inhibition and RVU120 exposure was observed. Conclusion: In the ongoing phase 1 trial, RVU120 shows clinical activity in both AML and HR-MDS, inducing RBC transfusion independence and blast reduction with a tolerable safety profile. Clearance of BM blasts including a formal CR were observed in patients treated at different dose levels. Relevant target inhibition is achieved from 110 mg onwards with expected higher pSTAT 5 inhibition with further dose escalation

Outcome of SARS-CoV-2-Infected Polish Patients with Chronic Lymphocytic Leukemia

Background. The severe acute respiratory syndrome coronavirus (SARS-CoV-2) has become the cause of a worldwide pandemic, and its clinical infection course in patients with hematological malignancies may be severe. Methods. We performed a retrospective study on 188 chronic lymphocytic leukemia patients (CLL) with COVID-19 infection. Results. At the time of infection 51 patients (27.1%) were treated with Bruton tyrosine kinase inhibitor (BTKi), 46 (24.5%) with anti-CD20 antibodies while 37 patients (19.7%) received venetoclax. In total, 111 patients (59.0%) required hospitalization and 50 patients (26.5%) died due to COVID-19. Patients with poor performance status (ECOG >1; p = 0.02), advanced age (>65 years; p = 0.04), low hemoglobin concentration (≤10 g/dl; p = 0.0001), low platelets (p = 0.003), and elevated lactate dehydrogenase level (LDH; p = 0.014) had an increased risk of death due to COVID-19. Neither CLL treatment status (treatment naïve vs. treated) nor the type of CLL-directed treatment had impact on the SARS-CoV-2 related risk of death. The multivariate survival analysis showed that advanced age (p = 0.009) and low platelet count (p = 0.0001) were associated with significantly shorter patients’ overall survival. Conclusions. SARS-CoV-2 infection in CLL patients is associated with poor outcome regardless of administered CLL-directed treatment