Limitations of VS38c labeling in the detection of plasma cell myeloma by flow cytometry.

Plasma cell myeloma (multiple myeloma [MM]) is a malignant neoplasm originating from the plasma cells. Besides other methods, flow cytometric analysis of the patient's bone marrow aspirate has an important role in the diagnosis and also in the response assessment. Since the cell surface markers, used for identifying abnormal plasma cells, are expressed diversely and the treatment can also alter the phenotype of the plasma cells, there is an increasing demand for new plasma cell markers. VS38c is a monoclonal antibody that recognizes the CLIMP-63 protein in the membrane of the endoplasmic reticulum. CLIMP-63 is known to be expressed at high levels in normal and pathologic plasma cells in the bone marrow, thus VS38c antibody can be used to identify them. Although VS38c staining of plasma cells is reported to be constant and strong even in myeloma, we were wondering whether sample preparation can affect the staining. We have investigated the effect of different permeabilization agents and washing of the cells on the quality of the VS38c staining and found that in many cases the staining is inadequate to identify the plasma cells. We measured the VS38c staining of the bone marrow aspirates of 196 MM patients and observed that almost all cases showed bright staining with VS38c. However, permeabilization with mild detergent resulted in the appearance of a significant VS38cdim subpopulation, which showed increased sensitivity to mechanical stress (centrifugation). Our results indicate that VS38cdim MM cells can appear due to the improper permeabilization of the endoplasmic reticulum and this finding raises the possibility of the existence of a plasma cell subpopulation with different membrane properties. The significance of this population is unclear yet, but these cells can be easily missed with VS38c staining and can be lost due to centrifugation-induced lysis during sample preparation.

Coexistence of aortic valve stenosis and cardiac amyloidosis: echocardiographic and clinical significance.

BACKGROUND: Left ventricular hypertrophy and diastolic dysfunction are common echocardiographic features of both aortic valve stenosis (AS) and cardiac amyloidosis (CA). These two different entities therefore may mask each other. From recent years, there is a growing body of evidence about the relatively high incidence of wild-type transthyretin (wtTTR) amyloidosis in AS, but there are scarce data on the prevalence of AS in CA, particularly in AL-type amyloidosis. The echocardiographic approach to these patients is not obvious, and not evidence based. We aimed to study the prevalence, severity, and type of AS in patients with CA and also to evaluate the potential of echocardiography in the diagnostic process. METHODS: Between January 2009 and January 2019, we retrospectively analyzed the clinical and echocardiographic data, and the echocardiographic work up of 55 consecutive CA patients. RESULTS: 80% of our CA patients had AL amyloidosis. We identified 5 patients (9%) with moderate to severe AS: two with moderate AS and three with low-flow, low-grade AS (LFLG AS). Further analysis of the latter three patients with dobutamine stress echocardiography revealed pseudo-severe LFLG AS in two, and true-severe AS in one patient. CONCLUSION: The prevalence of moderate to severe AS is 9% in our population of CA patients, the majority of whom have AL amyloidosis. Dobutamine echocardiography seems to be appropriate for the further characterization of patients with LFLG AS, even with normal ejection fraction.

The effect of microenvironmental factors on the development of myeloma cells.

Multiple myeloma (MM) is a clonal B-cell malignancy characterized by the accumulation of monoclonal plasma cells (PCs) in the bone marrow and other tissues. Although there are several new therapies, MM remains fatal. The interaction between MM cells and the bone marrow microenvironment promotes drug resistance and cancer cells survival. In our present work, we compared the antigen expression pattern of normal and pathological PCs and investigated the possible connections between various surface receptors, adhesion molecules, and recurrent genetic aberrations. We showed that the expression of CD29, CD27, and CD81 is lower in MM cells than in normal PCs. We found correlation of chromosome 11 hyperdiploidity and the decrease of CD27 expression. We demonstrated that MM cells with CD20 positivity also have CD28 expression. Multiple myeloma patients with active CD29 showed better response to treatment. Our results suggest that these changes may result in an alteration of the interaction between stromal cell and MM cell facilitating cell survival and the development of a more aggressive and resistant phenotype.

[Thalidomide therapy in relapsed diffuse large B-cell lymphoma in elderly patients. Three cases]. / Thalidomidkezelés relabált, diffúz nagy B-sejtes lymphomában idos betegekben. Három eset bemutatása.

Diffuse large B-cell lymphoma (DLBCL), a high-grade lymphoproliferative disease, is the most common lymphoma in adults, representing 31% of non-Hodgkin lymphomas (NHL). In elderly patients treatment is problematic because of the high toxicity of standard chemotherapy protocols, especially in relapsed cases, where high-dose chemotherapy and haematopoietic stem cell transplantation would be the best choice. More and more data is becoming available on alternative treatment of refractory/relapsed NHL, including studies on the positive effect of thalidomide and second generation IMiDs in DLBCL, which are already part of the standard treatment protocol in myeloma multiplex and myelodysplasia. The broadening use of IMiDs is due to their anti-angiogenetic, immunmodulatory and anti-inflammatory properties. In addition, a component of the E3-ubiquitin ligase complex, named cereblon, has been described in 2010 as the molecular effector of the thalidomide signal transduction pathway. We initiated thalidomide treatment in three elderly patients with relapsed DLBCL. In two cases, patients had CNS involvement, in the third case the patient had primary mediastinal disease. Patients received 100 mg thalidomide in combination with corticosteroids. Two patients showed an excellent response reaching complete remission on imaging; these patients are progression-free 12 and 20 months after the beginning of treatment. One patient with CNS involvement progressed and deceased despite therapy. According to the literature, IMiDs have significant activity in relapsed DLBCL. Our case-report presents promising results in an elderly patient population with aggressive relapsed NHL that usually has very poor outcome, as high-toxicity treatment cannot be given to these patients. Consequently, because of its efficiency, low-cost and low-toxicity, it is recommended to consider thalidomide therapy in elderly patients with high-grade DLBCL. Orv Hetil. 2017; 158(41): 1642-1648.

[Management of multiple myeloma in Hungary in 2016]. / A myeloma multiplex megközelítése Magyarországon 2016-ban.

The last decade has witnessed a dramatic progress in the treatment of multiple myeloma. Both the chemotherapy protocols and the supportive therapy options have improved significantly since the publication of the previous Hungarian national guideline. An increasing proportion of patients now reach a durable response and cure became a potential option for some. The aim of the authors was to adapt the international guidelines to the specific circumstances of the Hungarian healthcare system in the light of the most recent developments.

NFKB1 -94ins/delATTG polymorphism is a novel prognostic marker in first line-treated multiple myeloma.

Nuclear factor kappa B (NFKB) plays an important role in multiple myeloma (MM), and bortezomib affects this pathway. We retrospectively analysed the effect of the NFKB1 -94ins/delATTG polymorphism on the survival of 295 MM patients treated at a single centre. The median progression-free survival (PFS) was 790 (659-921) d in patients with NFKB1 homozygous insertion genotype (I/I, n = 99) and 624 (515-733) d in deletion-carriers (I/D&D/D, n = 196, P = 0·013). In multivariate analysis, I/I carriers showed a favourable PFS compared to I/D&D/D with a hazard ratio of 0·622 (0·457-0·847), P = 0·003, in addition to international staging system (ISS) score, fluorescence in situ hybridization (FISH) risk score, age and bortezomib treatment. I/I patients benefited more from bortezomib treatment [PFS 902 (703-1101) and 580 (343-817), P = 0·008] than I/D&D/D patients [PFS 659 (487-831) and 488 (323-653), P = 0·531]; in addition the beneficial effect of low ISS score was not observed in the I/D&D/D group [PFS 639 (454-824) and 650 (458-842), P = 0·226], while it was clear in I/I patients [PFS 1140 (803-1477) and 580 (408-752), P < 0·001]. We conclude that homozygous carriers of the insertion allele of the NFKB1 -94ins/delATTG polymorphism have a better prognosis and probably benefit more from bortezomib treatment than MM patients carrying the deletion allele.

[How long does a myeloma patient currently wait for the diagnosis in Hungary?]. / Mennyit vár ma Magyarországon egy myelomás beteg a diagnózisig?

INTRODUCTION: Long delays with the diagnosis of myeloma are common. So far there has not been a comprehensive study on this issue in Hungary. AIM: The aim of the authors was to analyze the waiting time from their first symptoms to the diagnosis of myeloma. METHOD: 193 myeloma patients treated in one large tertiary referral hematology centre in Hungary were included. RESULTS: The median time was 4.1 months (0-35.4) until diagnosis, and 5.2 months (0-35.4) until treatment. The delay was longer in patients with better prognosis (early stage, low cytogenetic risk), in nonsecretory disease and in 5 patients with amyloidosis. There was no significant relationship between the delay and the survival. CONCLUSIONS: Considering the results of the present study and earlier literature data, the authors look for possibilities to improve the diagnostic delay. They think that the key to an earlier diagnosis is in the hands of the primary care physicians as they see the patients first and decide whether it is necessary to refer them to further test and to which specialty. Helping them with diagnostic algorithms, clear referring pathways, fast tracking patients with urgent problems, and making serum electrophoresis universally available in the primary care could help to reduce the time that myeloma patients spend waiting.

Synthesis of tartaric acid analogues of FR258900 and their evaluation as glycogen phosphorylase inhibitors.

Di-O-cinnamoylated, -p-coumaroylated, and -feruloylated d-, l- and meso-tartaric acids were synthesized as analogues of the natural product FR258900, a glycogen phosphorylase (GP) inhibitor with in vivo antihyperglycaemic activity. The new compounds inhibited rabbit muscle GP in the low micromolar range, and bound to the allosteric site of the enzyme. The best inhibitor was 2,3-di-O-feruloyl meso-tartaric acid and had Ki values of 2.0µM against AMP (competitive) and 3.36µM against glucose-1-phosphate (non-competitive).

Synthesis, enzyme kinetics and computational evaluation of N-(ß-D-glucopyranosyl) oxadiazolecarboxamides as glycogen phosphorylase inhibitors.

All possible isomers of N-ß-D-glucopyranosyl aryl-substituted oxadiazolecarboxamides were synthesised. O-Peracetylated N-cyanocarbonyl-ß-D-glucopyranosylamine was transformed into the corresponding N-glucosyl tetrazole-5-carboxamide, which upon acylation gave N-glucosyl 5-aryl-1,3,4-oxadiazole-2-carboxamides. The nitrile group of the N-cyanocarbonyl derivative was converted to amidoxime which was ring closed by acylation to N-glucosyl 5-aryl-1,2,4-oxadiazole-3-carboxamides. A one-pot reaction of protected ß-D-glucopyranosylamine with oxalyl chloride and then with arenecarboxamidoximes furnished N-glucosyl 3-aryl-1,2,4-oxadiazole-5-carboxamides. Removal of the O-acetyl protecting groups by the Zemplén method produced test compounds which were evaluated as inhibitors of glycogen phosphorylase. Best inhibitors of these series were N-(ß-D-glucopyranosyl) 5-(naphth-1-yl)-1,2,4-oxadiazol-3-carboxamide (Ki = 30 µM), N-(ß-D-glucopyranosyl) 5-(naphth-2-yl)-1,3,4-oxadiazol-2-carboxamide (Ki =33 µM), and N-(ß-D-glucopyranosyl) 3-phenyl-1,2,4-oxadiazol-5-carboxamide (Ki = 104 µM). ADMET property predictions revealed these compounds to have promising oral drug-like properties without any toxicity.

[Venetoclax-based salvage in multiple myeloma with (11;14) translocation after suboptimal response to first-line therapy]. / Venetoclaxalapú mentokezelés (11;14)-transzlokációs myeloma multiplexben az elso vonalbeli kezelésre adott nem megfelelo válasz esetén.

INTRODUCTION: Multiple myeloma is one of the most common hematologic malignancies, with approximately 400 patients diagnosed in Hungary annually. Novel therapies emerging in the last decade have made a great impact on most patients' survival, however, those responding poorly to standard first-line therapy and failing to proceed to stem cell transplantation face a dire prognosis. Venetoclax, a selective Bcl-2 inhibitor has been shown very effective in the treatment of relapsed/refractory t(11;14) patients, but there are only a few studies about its safety and efficacy when used as salvage in the second line. OBJECTIVE: The aim of our study was to analyze the data of t(11;14) patients treated with venetoclax salvage at our clinic and to evaluate its efficacy. METHOD: Between 2017 and 2021, 13 patients received venetoclax therapy at our clinic after suboptimal response to frontline treatment, whose data we analyzed retrospectively. RESULTS: Adverse prognostic markers were very prevalent in our group, 4 of our patients had del(17p), 5 had amp(1q21) and 6 had stage 3. Nevertheless, all 13 patients responded well to venetoclax therapy, with 6 reaching very good partial response and 7 complete response. All eligible patients (10) could proceed to transplantation. After median 38 months follow up, neither median progression-free, nor median overall survival was reached, since only 3 patients progressed and 1 died. CONCLUSION: We have shown that when salvage is needed for t(11;14) patients who respond suboptimally to standard frontline therapy, venetoclax is a remarkably good option. Orv Hetil. 2023; 164(23): 894-899.

Soluble B-cell maturation antigen as a monitoring marker for multiple myeloma.

Objective: Response to treatment in multiple myeloma (MM) is routinely measured by serum and urine M-protein and free light chain (FLC), as described by the International Myeloma Working Group (IMWG) consensus statement. A non-negligible subgroup of patients however present without measurable biomarkers, others become oligo or non-secretory during recurrent relapses. The aim of our research was to evaluate soluble B-cell maturation antigen (sBCMA) as a monitoring marker measured concurrent with the standard monitoring in MM patients at diagnosis, at relapse and during follow up, in order to establish its potential usefulness in oligo and non-secretory disease. Method: sBCMA levels were measured in 149 patients treated for plasma cell dyscrasia (3 monoclonal gammopathy of unknown significance, 5 smoldering myeloma, 7 plasmacytoma, 8 AL amyloidosis and 126 MM) and 16 control subjects using a commercial ELISA kit. In 43 newly diagnosed patients sBCMA levels were measured at multiple timepoints during treatment, and compared to conventional IMWG response and progression free survival (PFS). Results: sBCMA levels among control subjects were significantly lower than among newly diagnosed or relapsed MM patients [20.8 (14.7-38.7) ng/mL vs. 676 (89.5-1,650) and 264 (20.7-1,603) ng/mL, respectively]. Significant correlations were found between sBCMA and the degree of bone marrow plasma cell infiltration. Out of the 37 newly diagnosed patients who have reached partial response or better per IMWG criteria, 33 (89%) have had at least a 50% drop in sBCMA level by therapy week 4. Cohorts made similarly to IMWG response criteria-achieving a 50% or 90% drop in sBCMA levels compared to level at diagnosis-had statistically significant differences in PFS. Conclusion: Our results confirmed that sBCMA levels are prognostic at important decision points in myeloma, and the percentage of BCMA change is predictive for PFS. This highlights the great potential use of sBCMA in oligo- and non-secretory myeloma.

Genetic identification of members of the prominent Báthory aristocratic family.

The Báthory family was one of the most powerful noble families in the medieval Hungarian Kingdom. Their influence peaked during the Ottoman occupation of Hungary, when the only partially autonomous region of the country was Transylvania, under Turkish protectorate. Several members of the family became Princes of Transylvania, and one of them, István Báthory, was also the elected King of Poland. We hereby present the first genetic data about this extinct family. Archaeological excavations in Pericei, a settlement now part of Romania, revealed the former family chapel of the Báthory family. Through this work, two Báthory family members were successfully identified among the 13 skeletons found at the site. The presence of Y chromosome haplogroup R-S498 fits the historical account describing the family's German (Swabian) origins. Their genomic composition also indicates a family of Germanic origin that intermixed with medieval Hungarians.

[How did the survival of acute myeloid leukemia change over the last ten years in our unit?] / Hogyan változott az akut myeloid leukaemiás betegek túlélése a terápiás lehetoségek bovülésével az elmúlt 10 évben klinikánkon?

INTRODUCTION: Acute myeloid leukemia (AML) is a hematological malignancy with high mortality rate. The treatment is especially challenging in patients older than 65 years, which is the large majority of those. For patients unfit for intensive chemotherapy regimens, only palliative cytoreduction and basic supportive care used to be the options in our unit. However, from 2018, the azacitidine-venetoclax combination has been a new therapeutic alternative. This treatment resulted in marked survival benefit in clinical trials, however, its impact on the daily clinical practice and the entire patient population is unclear. OBJECTIVE: Our goal was to evaluate how the application of azacitidine-venetoclax changed the treatment and survival of AML patients in our practice. METHOD: We retrospectively analyzed the available clinical data of all AML patients treated consecutively between January 1, 2011 and December 31, 2021 at the 3rd Department of Internal Medicine (from 2020 onward called Department of Internal Medicine and Hematology), examining their treatment depending on the time period of therapy (2011-2017 and 2018-2021). Patients with acute promyelocytic leukemia were excluded. RESULTS: 423 patients were diagnosed during this period. The number of cases showed a marked increase: in the first 7 years of our study, 184 patients were diagnosed, while this rose to 239 during the subsequent 4 years. The median age of patients was 67.6 years, with more than 60% of patients aged over 65. An improving trend can be observed in the overall survival: between 2011 and 2017, the median overall survival was 4.8 ± 0.9 months, while between 2018 and 2021, it was 8.3 ± 1.4 months (p = 0.051). Moreover, in the case of patients over 65 there was a significant overall survival improvement: 3.1 ± 0.5 vs. 4.9 ± 0.6 months (p = 0,01). The main factor behind this improvement could be that a large proportion of over 65 patients previously only fit for supportive care could now be treated with azacitidine-venetoclax: the percentage of actively treated patients grew from 57.1% to 75.3% in the second period. CONCLUSION: The survival of patients unfit for curative therapy and older than 65 showed a steady increase which can be attributed to the introduction of new therapeutic alternatives. Orv Hetil. 2023; 164(45): 1787-1794.

Evaluation of Retinal Blood Flow in Patients with Monoclonal Gammopathy Using OCT Angiography.

BACKGROUND: Monoclonal gammopathy (MG) is characterized by monoclonal protein overproduction, potentially leading to the development of hyperviscosity syndrome. OBJECTIVE: To assess retinal circulation using optical coherence tomography angiography (OCTA) parameters in patients with monoclonal gammopathy. METHODS: OCTA measurements were performed using the Optovue AngioVue system by examining 44 eyes of 27 patients with MG and 62 eyes of 36 control subjects. Superficial and deep retinal capillary vessel density (VD SVP and DVP) in the whole 3 × 3 mm macular and parafoveal area, foveal avascular zone (FAZ) area, and central retinal thickness (CRT) were measured using the AngioAnalytics software. The OCTA parameters were evaluated in both groups using a multivariate regression model, after controlling for the effect of imaging quality (SQ). RESULTS: There was no significant difference in age between the subjects with monoclonal gammopathy and the controls (63.59 ± 9.33 vs. 58.01 ± 11.46 years; p > 0.05). Taking into account the effect of image quality, the VD SVP was significantly lower in the MG group compared to the control group (44.54 ± 3.22% vs. 46.62 ± 2.84%; p < 0.05). No significant differences were found between the two groups regarding the other OCTA parameters (p > 0.05). CONCLUSIONS: A decreased superficial retinal capillary vessel density measured using OCTA in patients with MG suggests a slow blood flow, reduced capillary circulation, and consequent tissue hypoperfusion. An evaluation of retinal circulation using OCTA in cases of monoclonal gammopathy may be a sensitive method for the non-invasive detection and follow-up of early microcirculatory dysfunction caused by increased viscosity.

Outcome of Second Primary Malignancies Developing in Multiple Myeloma Patients.

BACKGROUND: There is an increased risk of second primary malignancies (SMPs) in patients with multiple myeloma (MM). This multinational 'real-world' retrospective study analyzed the characteristics and outcomes of MM patients that developed SPMs. RESULTS: 165 patients were analyzed: 62.4% males; 8.5% with a prior cancer; 113 with solid SPMs, mainly ≥stage 2; and 52 with hematological SPM (hemato-SPM), mainly MDS/AML. Patients with hemato-SPM were younger (p = 0.05) and more frequently had a prior AutoHCT (p = 0.012). The time to SPM was shorter in the older (>65 years) and more heavily pretreated patients. One hundred patients were actively treated at the time of SPM detection. Treatment was discontinued in 52, substituted with another anti-MM therapy in 15, and continued in 33 patients. Treatment discontinuation was predominant in the patients diagnosed with hemato-SPM (76%). The median OS following SPM detection was 8.5 months, and the main cause of death was SPM. A poor ECOG status predicted a shorter OS (PS 3 vs. 0, HR = 5.74, 2.32-14.21, p < 0.001), whereas a normal hemoglobin level (HR = 0.43, 0.19-0.95, p = 0.037) predicted longer OS. CONCLUSIONS: With the continuing improvement in OS, a higher proportion of MM patients might develop SPM. The OS following SPM diagnosis is poor; hence, frequent surveillance and early detection are imperative to improve outcomes.

Lifelong vaccination strategy as a tool against pandemics in Hungary / Élethosszan át tartó oltási stratégia mint eszköz a pandémiák elleni védekezésben Magyarországon

Due to various factors, the chances of infectious disease emergence or re-emergence have increased in the 21st century, thus, the likelihood of new emerging pandemics has also increased. The COVID-19 pandemic, which appeared in 2019, has highlighted that certain new and re-emerging infectious diseases - in the case of lack or delay in effective measures - can spread very rapidly. The main tool for the fight against infectious diseases is immunization through vaccination. While focusing on the personal health, public health, economic and societal benefits of a lifelong immunization strategy, especially in light of the aging society, the goal of this paper is to present the benefits of vaccines. In order to increase the added value of vaccinations it is recommended to create a lifelong immunization strategy.

Corneal Densitometry and In Vivo Confocal Microscopy in Patients with Monoclonal Gammopathy-Analysis of 130 Eyes of 65 Subjects.

BACKGROUND: Corneal imaging may support an early diagnosis of monoclonal gammopathy. The goal of our study was to analyze corneal stromal properties using Pentacam and in vivo confocal cornea microscopy (IVCM) in subjects with monoclonal gammopathy. PATIENTS AND METHODS: In our cross-sectional study, patients with monoclonal gammopathy (130 eyes of 65 patients (40.0% males; age 67.65 ± 9.74 years)) and randomly selected individuals of the same age group, without hematological disease (100 eyes of 50 control subjects (40.0% males; age 60.67 ± 15.06 years)) were included. Using Pentacam (Pentacam HR; Oculus GmbH, Wetzlar, Germany), corneal stromal light scattering values were obtained (1) centrally 0-2 mm zone; (2) 2-6 mm zone; (3) 6-10 mm zone; (4) 10-12 mm zone. Using IVCM with Heidelberg Retina Tomograph with Rostock Cornea Module (Heidelberg Engineering, Heidelberg, Germany), the density of hyperreflective keratocytes and the number of hyperreflective spikes per image were manually analyzed, in the stroma. RESULTS: In the first, second and third annular zone, light scattering was significantly higher in subjects with monoclonal gammopathy, than in controls (p ≤ 0.04). The number of hyperreflective keratocytes and hyperreflective spikes per image was significantly higher in stroma of subjects with monoclonal gammopathy (p ≤ 0.012). CONCLUSIONS: Our study confirms that increased corneal light scattering in the central 10 mm annular zone and increased keratocyte hyperreflectivity may give rise to suspicion of monoclonal gammopathy. As corneal light scattering is not increased at the limbal 10-12 mm annular zone in monoclonal gammopathy subjects, our spatial analysis provides evidence against the limbal origin of corneal paraprotein deposition. Using IVCM, stromal hyperreflective spikes may represent specific signs of monoclonal gammopathy.

Pomalidomide Treatment in Relapsed/Refractory Multiple Myeloma Patients-Real-World Data From Hungary.

Pomalidomide is a third generation immunomodulatory drug in the treatment of refractory and relapsed multiple myeloma patients. Our aim was to investigate the efficacy and safety of pomalidomide therapy in a real world setting. Eighty-six Hungarian patients were included, 45 of whom received pomalidomide ± an alkylating agent, while in 38 of them pomalidomide was combined with a proteasome inhibitor. 56 patients (65%) showed any response to the treatment with 18 complete or very good partial remissions and 38 partial remissions. At a median duration of follow-up of 18.6 months, the median progression-free survival (PFS) was 9.03 months, while the median overall survival (OS) was 16.53 months in the whole cohort. Patients with early stage disease (R-ISS 1 and 2) had better survival results than those with stage 3 myeloma (p = 0.002). Neither the number of prior treatment lines, nor lenalidomide refractoriness had a significant impact on PFS. PFS was found similar between the cohort of patients with impaired renal function and the cohort without kidney involvement. During the study, eight mortal infections and two fatal bleeding complications occurred, however, mild hematologic and gastrointestinal toxicities were identified as the most frequent adverse events. The results of our investigations confirm that pomalidomide is an effective treatment option for relapsed/refractory MM, besides, the safety profile is satisfactory in subjects with both normal and impaired renal function.

Cardiac Amyloidosis with Normal Wall Thickness: Prevalence, Clinical Characteristics and Outcome in a Retrospective Analysis.

Background: Cardiac amyloidosis (CA) is a rare, progressive, infiltrative cardiac disease. Light chain (AL) and transthyretin (ATTR) amyloidosis are in the background in almost all cases. New, easily available diagnostic tools and recently introduced novel therapies for both types of CA put this disease into the field of interest. Increased left ventricular wall thickness (IWT) detected by echocardiography is generally thought to be a necessary part of the diagnosis. We aimed to determine the proportion of CA patients without IWT, and to define the clinical characteristics of this cohort. Methods: In an academic tertiary center for CA, we identified patients diagnosed and treated for CA between January 2009 and February 2022. In a retrospective analysis we defined the proportion of patients with (≥12 mm) and without (<12 mm) IWT, and described their clinical features. Results: We identified 98 patients suitable for the analysis. In total, 70 had AL and 27 ATTR CA; 89 patients had CA with IWT and 9 patients (9%) had CA without IWT. All non-IWT patients had AL type CA. Both group of patients had clinically significant disease, which is supported by the relevant elevation in cardiac biomarker levels. There was no difference between the outcome of the two groups. Conclusion: Patients without IWT form a relevant subgroup among those with CA. Our results suggest that diagnostic algorithms and criteria should take these individuals into consideration, and, therefore, give them access to effective treatments.

Targeted Venetoclax Therapy in t(11;14) Multiple Myeloma: Real World Data From Seven Hungarian Centers.

Despite the introduction of novel agents, multiple myeloma remains incurable for most patients, necessitating further therapeutic options. Venetoclax, a selective BCL-2 inhibitor, had shown promising results in patients with translocation t(11;14), but questions remain open about its optimal use. We have contacted all Hungarian haematology centers for their experience treating t(11;14) myeloma patients with venetoclax. 58 patients were reported. 37 received venetoclax in the relapsed/refractory setting with few or no other therapeutic options available. 21 patients started venetoclax as salvage after failing to achieve satisfactory response to first line therapy. In the relapsed/refractory setting objective response rate (ORR) was 94%, median progression-free survival (PFS) 10.0 months and median overall survival (OS) 14.6 months. In reinduction patients, ORR was 100%, median PFS and OS were not reached. Importantly, we found no adverse effect of high risk features such as deletion 17p or renal failure, in fact renal failure ameliorated in 42% of the cases, including three patients who became dialysis independent. Our study also reports the highest number of plasma cell leukemia cases successfully treated with venetoclax published in literature, with refractory plasma cell leukemia patients achieving a median PFS of 10.0 and a median OS of 12.2 months.