135 results on '"V, Maisnar"'
Search Results
2. P967: TUMOR BURDEN AS A CRITICAL PROGNOSTIC FACTOR OF PRIMARY EXTRAMEDULLARY DISEASE
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M. Vlachová, M. Štork, S. Ševčíková, T. Jelínek, J. Minařík, J. Radocha, P. Krhovská, L. Pospíšilová, I. Špička, J. Straub, P. Pavlíček, A. Jungová, V. Sandecká, V. Maisnar, R. Hájek, and L. Pour
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
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- View/download PDF
3. Analýza častějšího výskytu mnohočetného myelomu ve východních Čechách.
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L., Šolcová and V., Maisnar
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IMMUNOGLOBULIN light chains , *MULTIPLE myeloma , *MONOCLONAL gammopathies , *CLINICAL biochemistry , *B cells , *LYMPHOPROLIFERATIVE disorders , *MONOCLONAL antibodies - Abstract
Monoclonal gammopathy are a heterogeneous group of disorders. They are characterized by proliferation of clonal differentiated B-cells producing the monoclonal immunoglobulin (MIG). Monoclonal immunoglobulin consists of both an intact immunoglobulin molecule or also only of its structural component, i.e. light chain kappa or lambda, rarely heavy chain. The most common monoclonal gammopathy is monoclonal gammopathy of unknown (undetermined) significance. Every patient with MGUS should be monitored regularly. In recent years, the early diagnosis of MGUS has become increasingly important due to the frequency of monoclonal gammopathy in general and especially the most serious of them - multiple myeloma. A higher incidence of monoclonal gammopathies and especially MM in Czech Republic is apparent from the available data of the National Cancer Registry. The subject of our communication is the fact, that in East Bohemia region (especially in the Trutnov and Nachod regions), according to these data, the highest frequency of malignant lymphoproliferative disorders is recorded. Therefore, we focused on diagnostics and monitoring over time in patients with MGUS, who were detected by the department of clinical biochemistry of the regional hospital in Trutnov as part of a routine examination. In a 10-year follow-up of patients with newly diagnosed monoclonal gammopathy of undetermined significance we monitored their further development over time and also on the frequency of transformation in malignant lymphoproliferative disorders, especially multiple myeloma in the district Trutnov. [ABSTRACT FROM AUTHOR]
- Published
- 2021
4. PF608 ANCHOR (OP-104): A PHASE 1 STUDY UPDATE OF MELFLUFEN AND DEXAMETHASONE PLUS BORTEZOMIB OR DARATUMUMAB IN RELAPSED/REFRACTORY MULTIPLE MYELOMA PATIENTS REFRACTORY TO AN IMID OR A PROTEASOME INHIBITOR
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L. Pour, Enrique M. Ocio, M. Granell, J. Martinez-Lopez, M. Sydvander, M.V. Mateos, A. Oriol, R. Hajek, Christian Jacques, Jan Straub, P.G. Richardson, M. Norkin, Y.A. Efebera, V. Maisnar, C. Byrne, L. Karlin, K. Le Du, J.-R. Eveillard, J. Delaunay, and V. Ribrag
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Bortezomib ,business.industry ,Daratumumab ,Hematology ,medicine.disease ,Refractory ,Relapsed refractory ,Cancer research ,medicine ,Proteasome inhibitor ,business ,Multiple myeloma ,Dexamethasone ,medicine.drug - Published
- 2019
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5. PF626 HEALTH-RELATED QUALITY OF LIFE (HRQOL) OUTCOMES OF ORAL IXAZOMIB MAINTENANCE THERAPY POST AUTOLOGOUS STEM CELL TRANSPLANT (ASCT) IN NEWLY DIAGNOSED MULTIPLE MYELOMA (NDMM) FROM TOURMALINE-MM3
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M.A. Dimopoulos, K. Suryanarayan, S V Rajkumar, Ivan Spicka, Dorothy Romanus, N. Abildgaard, Lauren E. Cain, D. Odom, H. Goldschmidt, V. Maisnar, Fredrik Schjesvold, Philip A. Rowlings, and A. Gnanasakthy
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Health related quality of life ,Oncology ,medicine.medical_specialty ,business.industry ,Hematology ,Newly diagnosed ,medicine.disease ,Ixazomib ,chemistry.chemical_compound ,Maintenance therapy ,chemistry ,Internal medicine ,medicine ,Stem cell ,business ,Multiple myeloma - Published
- 2019
- Full Text
- View/download PDF
6. Doporučení České společnosti klinické biochemie a České myelomové skupiny k laboratorní diagnostice monoklonálních gamapatií.
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J., Vávrová, P., Kušnierová, V., Maisnar, and L., Šolcová
- Published
- 2020
7. Monoclonal gammopathy of undeterminated significance: introduction and current clinical issues
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M, Klincová, V, Sandecká, A, Mikuláiová, J, Radocha, V, Maisnar, and R, Hájek
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Immunoglobulin M ,Disease Progression ,Humans ,Multiple Myeloma ,Monoclonal Gammopathy of Undetermined Significance ,Precancerous Conditions - Abstract
Monoclonal gammopathy of undetermined significance (MGUS) is a precancerosis comprising two different kinds of cancer: lymphoid/lymphoplasmocytoid MGUS and plasma cell MGUS that represents about 85% of all MGUS cases. This type of MGUS has low but persistent tendency to transform to malignant disease, mainly multiple myeloma (MM), with frequency of about 1% per year. Using known risk stratification models based on clinical parameters, it is possible to identify patients' groups with average rates of progression as low as 0.26% and as high as 12% per year. However, due to the lack of clear genetic and/or phenotypic markers distinguishing MGUS from MM, we are not able to predict if and when MGUS will progress to MM in individual patients. There are partially overlapping molecular pathogenic events shared by MGUS and MM. Better understanding of pathogenesis of MGUS and MM using molecular-genetic approaches will help disclose the mechanisms of myeloma genesis; it can be also useful for identification of novel molecular targets. The ultimate goal for the near future is to develop better markers for definition of high-risk MGUS patients who will be candidates for early treatment intervention.
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- 2011
8. [The role of procalcitonin in the differential diagnosis of fever in patiens with multiple myeloma]
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K, Machálková and V, Maisnar
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Calcitonin ,Male ,Fever ,Calcitonin Gene-Related Peptide ,Middle Aged ,Infections ,Diagnosis, Differential ,C-Reactive Protein ,Humans ,Female ,Protein Precursors ,Multiple Myeloma ,Biomarkers ,Aged - Abstract
Fever and elevated C-reactive protein are frequently found in hematooncological patients. It is sometimes difficult to distinguish between infectious fever and drug-related or tumour-associated fever. Tumour-related fever is not very common in multiple myeloma (unlike malignant lymphomas). C-reactive protein (CRP) is usually elevated simultaneously with fever and so it cannot be used in differential diagnosis of febrile states. There is another marker that provides information about the origins of the fever--rocalcitonin. We present cases of three patients that illustrate the significance of procalcitonin in patients with multiple myeloma.
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- 2011
9. [Lenalidomide in the treatment of multiple myeloma]
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K, Machálková and V, Maisnar
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Male ,Antineoplastic Agents, Hormonal ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Middle Aged ,Multiple Myeloma ,Lenalidomide ,Dexamethasone ,Thalidomide - Abstract
We present the case of a 58-year old patient with relapsed multiple myeloma, in which lenalidomide was used in combination with dexamethasone after the failure of previous treatment modalities. The progression of the myeloma was clinically manifested by painful swelling of the patient's left arm caused by an extensive osteolytic lesion of the bone. After one month of therapy with lenalidomide and dexamethasone, a significant decrease in the paraprotein level was detected. Later, the clinical finding on the left arm was normalized too and concurrently the X-ray image shows the production of new bone.
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- 2009
10. [Monoclonal gammopathies of undetermined significance]
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V, Krizalkovicová, V, Maisnar, L, Pour, J, Radocha, and R, Hájek
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Paraproteinemias ,Humans ,Monoclonal Gammopathy of Undetermined Significance - Abstract
Monoclonal gammopathy of undetermined significance (MGUS) is the most common type of monoclonal gammopathies. Genetic changes, various cytokines and bone marrow angiogenesis play an important role in the pathogenesis. As far as the malignant transformation of MGUS is concerned, size and type of the serum M-protein, serum kappa and lambda free light chain ratio and number of plasma cells in peripheral blood seem to play a predictive role. A new possible risk-stratification model predicting progression of MGUS to multiple myeloma or other related disorders was presented in 2006. The model takes three parametres in consideration, type and initial size of the serum M-protein and serum kappa and lambda ratio. Patients are divided into four risk groups with different risk of progression, from 5% at 20 years in low risk group to 58% in high risk group. The interval from MGUS diagnosis to the evolution of multiple myeloma or other related malignancies ranges from 1 to 30 years. Nevertheless, the risk of progression persists even after more than 30 years after MGUS diagnosis.
- Published
- 2008
11. [Myopathy and mixed hyperlipoproteinemia as the first symptom of systemic AL-amyloidosis]
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M, Tosovský, T, Soukup, P, Bradna, V, Maisnar, V, Tycová, J, Toms, and M, Prixová
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Male ,Hyperlipoproteinemias ,Muscular Diseases ,Liver Diseases ,Humans ,Amyloidosis ,Middle Aged - Abstract
Systemic AL-amyloidosis is a disorder brought about by the over-production and deposition of fragments of light immunoglobulin chains in tissues, the consequence of which is their functional impairment. The most often affected are the kidneys, the heart, the gastro-intestinal tract and the nervous system. We describe the case of a 57-year-old patient in whom a rare disorder of the striated muscle (am yloid myopathy) was present, as the first clinical indication of systemic AL-amyloidosis. The main symptoms were muscle weakness and an increase in laboratory signs of muscle lesion. The patient was monitored for several years and treated with a diagnosis of primary idiopathic polymyositis (the likely diagnosis according to the diagnostic criteria of Bohan and Peter). Only after some years did hepatomegaly appear with elevated liver transaminases and a diagnosis of systemic AL-amyloidosis was established on the basis of a liver biopsy. By additional staining of striated muscle preparations with a dye for amyloid (in accordance with Maldyk) amyloid myopathy was confirmed. In addition to muscle affection, mixed hyperlipoproteinemia was present from the beginning. This was probably the first indication ofamyloidosis. The case description points out the justified inclusion of systemic AL-amyloidosis in differential diagnosis of muscle weakness and signs of muscle lesion. Amyloidosis must be considered if in addition to myopathy there is also present a problem with any organ which can typically be affected by amyloidosis.
- Published
- 2008
12. [Laboratory identification of monoclonal immunoglobin]
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M, Tichý and V, Maisnar
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Electrophoresis ,Biomarkers, Tumor ,Paraproteinemias ,Humans ,Immunoglobulins - Abstract
In the last decade, laboratory diagnostics of monoclonal gammopathies has taken a huge step forward. The study takes a brief look at the methods currently being used, discussing their significance, the problems faced in their definition and interpretation. Among the primary clinical-biochemical methods, there are agarose electrophoresis and capillary electrophoresis. Immunofixation electrophoresis has completely replaced immunoelectrophoresis in determining immunoglobin classes and antigen types of paraprotein light chains. Immunofixation is more sensitive and quicker. The determining of the concentration of free light chains (non-secretory myeloma, AL amyloidosis, illness from light chains) has also found its place in the algorithm of laboratory methods used in monoclonal gammopathy. Out of the many prognostic factors, the combination beta2-microglobulin and albumin has been chosen as the easiest and the one with the highest informative value. The spectrum of laboratory examinations is completed by determining the viscosity of serum and identification of cryoglobulins.
- Published
- 2008
13. [Recommendations for early identification of damage to the skeleton by malignant processes, and for early diagnosis of multiple myeloma]
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Z, Adam, J, Bednarík, J, Neubauer, R, Chaloupka, Z, Fojtík, J, Vanícek, L, Pour, Z, Cermákova, V, Scudla, V, Maisnar, J, Straub, M, Schützová, E, Gregora, M, Weinreb, K, Stuchlíková, J, Stanícek, R, Hájek, M, Krejcí, and J, Vorlícek
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Radiography ,Early Diagnosis ,Humans ,Multiple Myeloma ,Bone and Bones - Abstract
The number of newly diagnosed cases of multiple myeloma in the Czech Republic is about 3-4 per 100 000 persons per year. In the higher age groups, the incidence increases. Multiple myeloma is an illness that reacts well to treatment which can result in periods of remission lasting for years. Some of the patients are even able to return to work. A pre-requisite for successful treatment is early diagnosis and this is usually in the hands of first line physicians. This is the reason why the Czech Myeloma Group, in conjunction with neurologists, orthopedicians and radio diagnosticians has issued the following recommendations for first line physicians containing a more detailed description of the symptoms and the diagnostic pitfalls of the disease. This disease reminds a chameleon for the variety of its symptoms. For the sake of clarification, we shall divide multiple myeloma symptoms into five points, each of which is reason enough to warrant an examination to confirm or rule out a malignant cause of health problems (a negative result does not automatically mean exclusion). If any of the recommended examinations results positive, the diagnostic process must be continued, in which case a general practitioner refers the patient to a specialist health centre. Observing these recommendations should minimize the number of cases of late diagnosis. 1. Bone destruction symptoms. - Unexplained backache for more than one month in any part of spine even without nerve root irritability or without pain in other part of skeleton (ribs, hips, or long bones). - Pain at the beginning of myeloma disease is very similar to benigne common discopathy, however the intensity of backache is decreasing within one months in benigne disease. In the case of malignant process the intensity of bone pain is steadily increasing. - Immediate imaging and laboratory investigation are indicated by resting and night pain in spinal column or in any part of skeleton. - Backache with the sign of spinal cord or nerve compression should be sent for immediate X Ray, and focussed CT/MRI followed by acute surgery if needed. - Osteoporosis especially in men and premenopausal women. 2. Features of changed immunity or bone marrow function. Persistent and recurrent infection, typical is normochromic anaemia, with leucopenia and trombocytopenia. 3. Raised erythrocyte sedimentation rate even increase concentration of total plasma protein. 4. Impaired renal function. Increased level of creatinin or proteinuria, nephrotic syndrome with bilateral legs oedema. 5. Hypercalcemia with typical clinical symptoms (polyuria with dehydratation, constipation, nausea, low level conscience, coma). Every one from these points has to be reason for general medical doctor to start battery of tests: -X-ray of bones focused to painful area (mandatory before physiotherapy, local anaesthesia or other empiric therapy). If plain X-ray does not elucidate pain and symptoms are lasting more than one month, please consider all circumstances and results from laboratory investigation. This patient needs referral to the centre with MRI/CT facilities (CT or MRI is necessary investigation in case of nerve root or spine compression). -Investigation of erythrocyte sedimantion rate (high level of sedimentation of erythrocyte can indicate multiple myeloma). -Full blood count. -Basic biochemical investigation serum and urine: serum urea, creatinin, ionts including calcium, total protein, and albumin CRP (high concentration of total protein indicates myeloma, low level of albumin indicates general pathological process, similary increased concentration of fibrinogen, impaired renal function indicates myeloma kidney, however hypercalcemia is typical for highly aggressive myeloma). -Quantitative screening for IgG, IgM and IgA in serum (isolated raised level one of immunoglobulin with decreased level of the others indicates myeloma). -Common electrophoresis of serum is able to detect monoclonal immunoglobulin level at few gramm concentration. If all the laboratory investigation are in normal level the possibility that the current problems are multiple myeloma origine is smaller, but it does not exclude one of rare variant--non secretory myeloma (undifferentiated plasmocyt lost characteristic feature to produce monoclonal immunoglobulin). If any of tests indicate the possibility of myeloma, patient require urgent specialist referral to department with possibility to make diagnosis of malignant myeloma.
- Published
- 2008
14. Isotype class switching after transplantation in multiple myeloma
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V, Maisnar, M, Tichý, L, Smolej, P, Zák, J, Radocha, V, Palicka, J, Malý, and V, Bláha
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Adult ,Male ,Peripheral Blood Stem Cell Transplantation ,Paraproteinemias ,Graft vs Host Disease ,Middle Aged ,Prognosis ,Immunoglobulin Class Switching ,Immunoglobulin Isotypes ,Survival Rate ,Humans ,Transplantation, Homologous ,Female ,Multiple Myeloma ,Aged ,Paraproteins ,Retrospective Studies - Abstract
Switching of the paraprotein isotype or transient presence of oligoclonal bands detectable by serum immunofixation electrophoresis has been reported following not only transplantations, but also after intensive chemotherapy for leukemia. Retrospective analysis of 72 transplanted myeloma patients was carried out to determine the frequency and clinical significance of the appearance of abnormal proteins bands (APB) distinct from the original paraprotein. APB presence was observed in 31 patients (43%) already after the first autotransplant, the median interval from transplant was 2 months (range, 1 to 6 months). The most frequent occurrence of APB was observed after allogeneic transplantation. In the group of patients with APB presence more patients achieved complete remission (32.2% versus 17.1%), statistically significant differences were also established when we compared the percentage of surviving patients and overall survival, to the present date, among both groups of patients (p=0.03). All relapsed patients with previous isotype class switching had disease characterized by the same type of paraprotein as that detected at diagnosis. The development of APB is likely related to the recovery of impaired immunoglobulin production after transplantation. We confirmed favourable prognostic significance of this finding in transplanted myeloma patients.
- Published
- 2007
15. [Low-dose thalidomide in refractory and relapsing multiple myeloma]
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J, Radocha and V, Maisnar
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Adult ,Aged, 80 and over ,Male ,Recurrence ,Humans ,Female ,Middle Aged ,Multiple Myeloma ,Immunosuppressive Agents ,Aged ,Thalidomide - Abstract
Thalidomide is one of the drugs which are newly used in the therapy of multiple myeloma. Its immunomodulating action and a number of additional effects have been proven in the treatment of advanced and refractory stage of the disease. However, the best dosing scheme has not yet been discovered and is the subject of research in a number of clinical studies today.On a retrospective basis, we evaluated results for 59 patients with multiple myeloma who were treated with thalidomide in our facility (median dose of 100 mg), in monotherapy or in combination with corticosteroids, between 2000 and 2005. The objective was to determine the percentage of responses to treatment in patients at different stages of the disease. Response to treatment was evaluated in accordance with EBMT standards.Thalidomide was used as 2nd line therapy (1st relapse or primarily resistant disease) in 59% of cases (35 patients), and as 3rd line therapy (2nd relapse) in 37 % of cases (22 patients). 2 patients were receiving thalidomide as 4th line therapy. None of the patients had taken thalidomide as part of previous treatment. The response rate at 1st relapse (CR - complete remission, PR - partial remission, MR - minimum response) was 60% (21 patients), of which CR was recorded in 2 patients (6%), PR was recorded in 12 patients (35%) and MR in 6 patients (17%). The response rate at 2nd relapse was 45% (10 patients), of which CR was recorded in 3 patients (14%), PR in 1 patient (5%) and MR in 5 patients (23%). Even though we did not record any statistically significant difference in the response of the evaluated group of patients to the treatment with thalidomide at 1st and 2nd relapse, a higher percentage or progression during treatment (32% vs. 14%) was observed in patients at 2nd relapse. 2 patients treated with thalidomide at 3rd relapse did not have a satisfactory response to the treatment (progression or short stabilisation of the disease with subsequent progression). Only 3 patients (5%) of the evaluated group had to discontinue the treatment due to severe adverse events (neuropathy, allergic reaction, leukopenia). The follow up time for Thalidomide therapy ranged between 3 and 62 months for both groups (with a median of 10 months) and spanned from 3 to 60 months at 1st relapse (median of 12 months) and from 3 to 57 months at 2nd relapse (median of 6 months). No statistically significant differences were observed between the 1st and 2nd relapse groups of patients in terms of response rates or length of effect.Thalidomide is highly efficient in the treatment of multiple myeloma. The results of study document effectiveness of thalidomide regardless of the disease stage. Comparison of study data with the results of other studies shows that the effectiveness of lower doses we used is comparable with that of higher doses. The fact that lower doses of thalidomide reduce the incidence of adverse events is a clear advantage.
- Published
- 2007
16. [Role of percutaneous vertebroplasty and kyphoplasty in the treatment of oncology disorders of the spine]
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P, Ryska, S, Rehák, K, Odráka, V, Maisnar, J, Raupach, V, Málek, O, Renc, and K, Kaltofen
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Male ,Spinal Neoplasms ,Fractures, Compression ,Bone Cements ,Humans ,Polymethyl Methacrylate ,Spinal Fractures ,Female ,Kyphosis ,Aged - Abstract
The aim of the study is to present results of a prospective uncontrolled clinical study. Percutaneous vertebroplasty or kyphoplasty are minimally invasive methods based on polymethylmethacrylate (PMMA) bone cement application into the damaged vertebra. This leads to decrease of the pain and vertebral body stabilisation. Oncology disorders of the spine are relatively common, having a wide alternative of various methods of treatment. Patients, according to their findings and indication criteria, are treated surgically or conservatively, oncological treatment is usually based on radiotherapy. Authors discuss the role of these invasive procedures in the treating algorithm of patients with spinal metasthases and multiple myeloma.From September 2003 to December 2005, 21 percutaneous vertebroplasties in 14 patients, mean age 68.7 (47-80) year, were performed in our department. During one treatment session 1-2 vertebrae (total of 21 vertebrae) in level Th9 - L5 were treated. Vertebroplasties and kyphoplasty were performed under fluoroscopy guidance. Transpedicular acces was used. Totally, 3 asymptomatic complications were proved. As first, a bone cement leaked paravertebrally during L5 body treatment, as second, a bone cement leaked into paravertebral veins, and as third, a bone cement leaked into the intervertebral space. Visual analog scale (VAS) was 8.9 points before procedure, 1.9 point 3 months after procedure and 2.6 points 6 months after procedure. We did not prove a symptomatic or total complication.According to our experience, percutaneous vertebroplasty is an effective alternative treatment of painful oncologic spine disease.
- Published
- 2006
17. [Combination of imatinib and anagrelide in treatment of chronic myeloid leukemia in blastic phase]
- Author
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J, Voglová, V, Maisnar, M, Beránek, and L, Chrobák
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Male ,Thrombocytosis ,Antineoplastic Agents ,Middle Aged ,Piperazines ,Pyrimidines ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Benzamides ,Imatinib Mesylate ,Quinazolines ,Humans ,Blast Crisis ,Protein Kinase Inhibitors ,Platelet Aggregation Inhibitors - Abstract
Chronic myeloid leukemia in blast phase (BP) is resistant to chemotherapy and majority of patients die within 6 months. Inhibitor Bcr-Abl tyrosine kinase imatinib mesylate dramatically improved outcome of patients in chronic phase (CP) and is also effective in BP of CML. The prognosis of patients treated with imatinib in BP is worse than in CP. High platelet counts are often observed at diagnosis or in the subsequent course of the CML in about 25% of patients. Thrombohemorrhagic complications associated with the thrombocythemia may be serious. Anagrelide selectively reduces circulating platelets and is used in treatment of thrombocythemia in chronic myeloproliferative disorders. Efficacy and safety of combination imatinib mesylate with anagrelide was demonstrated in chronic and accelerated phase of CML. No study about the use of imatinib with anagrelide in BP has been found. 51-year-old white man with CML presented in blast phase was followed for 4 years. Imatinib mesylate in dose of 600 mg p.o. qd. was administered after the failure of initial chemotherapy. The patient was treated with imatinib for 45 months, 14.5 months in combination with anagrelide. Partial hematologic response in duration of 33 months was induced by imatinib, cytogenetic response was not reached. Imatinib-resistant thrombocythemia was controlled with anagrelide in dose of 0.5-1 mg p.o. qd. No thrombohemorrhagic complications were observed. The patient tolerated the combination of imatinib and anagrelide well and long-term survival gave him the chance of treatment with the new tyrosin kinase inhibitor (dasatinib).
- Published
- 2006
18. The significance of soluble CD138 in diagnosis of monoclonal gammopathies
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V, Maisnar, M, Tousková, M, Tichý, J, Krejsek, L, Chrobák, J, Voglová, and J, Malý
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Male ,Membrane Glycoproteins ,Syndecans ,Paraproteinemias ,Enzyme-Linked Immunosorbent Assay ,Middle Aged ,Prognosis ,Survival Analysis ,Diagnosis, Differential ,Humans ,Female ,Proteoglycans ,Syndecan-1 ,Multiple Myeloma ,Biomarkers - Abstract
Report is summary of the results of study designed to ascertain the significance of soluble CD138 (sCD138) assessment in patients with different monoclonal gammopathies. Previous studies have shown that sCD138 is shed from the surface of myeloma cells into serum and that this marker is a new independent prognostic parameter in multiple myeloma. In presented study was evaluated serum sCD138 level in 14 patients with monoclonal gammopathy of undetermined significance (MGUS) and in 17 patients with multiple myeloma (MM), all MM patients were treated by high-dose chemotherapy regimen with subsequent autologous transplantation of peripheral blood stem cells. To determine the sCD138 level we used a rapid and simple ELISA procedure. The mean serum sCD138 level of patients with MGUS was 32 ng/ml (range: 5-128). Soluble CD138 levels were elevated in the sera of 10 out of 17 (59%) multiple myeloma patients, the mean baseline sCD138 concentration was 1542 ng/ml (range: 10-17300). In spite of small number of patients the difference between MGUS and MM group was highly statistically significant (p0.001). Multiple myeloma patients with high level of sCD138 at diagnosis (cut-off value: 500 ng/ml) had worse prognosis despite of good response to chemotherapy in some of them (p=0.029). It seems that determination of sCD138 can be recommended as a helpful and reliable marker for differential diagnosis as well as prognosis of monoclonal gammopathies.
- Published
- 2006
19. [Bortezomib (Velcade) in relapsed/refractory multiple myeloma--the first experience in the Czech Republic]
- Author
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I, Spicka, R, Hájek, M, Vytrasová, V, Maisnar, E, Gregora, M, Schutzova, J, Straub, V, Scudla, Z, Adam, and P, Klener
- Subjects
Adult ,Aged, 80 and over ,Male ,Antineoplastic Agents ,Middle Aged ,Boronic Acids ,Bortezomib ,Recurrence ,Pyrazines ,Humans ,Female ,Protease Inhibitors ,Multiple Myeloma ,Aged - Abstract
Multiple myeloma is the second most prevalent and mostly fatal hematologic cancer. Further advances have been made in understanding the mechanisms involved in the myeloma pathogenesis and elucidation of critical signalling pathways as therapeutical targets. Proteasome inhibitors are the example of this new approach and bortezomib is the first agent in this class to enter clinical trials.In 6 hematological centers in Czech Republic 29 patients with refractory/relapsed myeloma had been treated with bortezomib (Velcade, Millennium Pharmaceuticals) in 2004. The initial dose 1.3 mg/m2 of Velcade was given, in 1 case the dose was adjusted due to pre-existing renal failure to 1 mg/m2. The response was achieved in 17 patients (59%). Four patients had complete, 11 partial and two minor responses. In 5 cases stabilization of disease was observed and 6 patients progressed during the therapy.Unfortunately, one patient died immediately after the start of therapy due to sepsis. The most common adverse events were thrombocytopenia, anaemia, neuropathy, gastrointestinal complication, renal failure and fatigue. Grade 4 adverse events occurred in 37.9% of patients (4x thrombocytopenia, 2x gastrointestinal, 2x renal failure, 1x sepsis, leucopenia, hepatopathy and anaemia, respectively). Peripheral neuropathic pain of grade 3 was reported in 4 cases, in one patient therapy had to be interrupted due to this complication. We confirmed promising results of phase II trials.
- Published
- 2005
20. Whole Exome Sequencing of Aberrant Plasma Cells in a Patient with Multiple Myeloma Minimal Residual Disease.
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M., Zatopkova, J., Filipova, T., Jelinek, P., Vojta, T., Sevcikova, M., Simicek, L., Rihova, R., Bezdekova, K., Growkova, Z., Kufova, J., Smejkalova, M., Hajduch, L., Pour, J., Minarik, A., Jungova, V., Maisnar, F., Kryukov, and R., Hajek
- Published
- 2017
- Full Text
- View/download PDF
21. Asymp tomatic and Treatment-requiring Multiple Myeloma - Data from the Czech Registry of Monoclonal Gammopathies.
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L., Brozova, J., Jarkovsky, L., Pour, J., Minarik, A., Jungova, E., Gregora, I., Spicka, V., Maisnar, and R., Hajek
- Published
- 2017
- Full Text
- View/download PDF
22. Czech Registry of Monoclonal Gammopathies - Technical Solution, Data Collection and Visualisation.
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L., Brozova, D., Schwarz, I., Snabl, J., Kalina, B., Pavlickova, M., Komenda, J., Jarkovsky, P., Nemec, D., Horinek, Z., Stefanikova, L., Pour, R., Hajek, and V., Maisnar
- Published
- 2017
- Full Text
- View/download PDF
23. Epidemiology of Multiple Myeloma in the Czech Republic.
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D., Maluskova, I., Svobodova, M., Kucerova, L., Brozova, J., Muzik, J., Jarkovsky, R., Hajek, V., Maisnar, and L., Dusek
- Published
- 2017
- Full Text
- View/download PDF
24. [Angiogenesis and antiangiogenic cancer therapy]
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L, Pour, R, Hájek, T, Buchler, V, Maisnar, and L, Smolej
- Subjects
Neovascularization, Pathologic ,Neoplasms ,Humans ,Angiogenesis Inhibitors - Abstract
Physiologic angiogenesis takes place during tissue growth and repair, during the female reproductive cycle, and during fetal development. Angiogenesis is also required for tumor growth and metastasis and, therefore, represents an exciting target for cancer treatment. Angiogenesis is a complex process that is tightly regulated by pro- and antiangiogenic growth factors. Pathologic angiogenesis is characterized by either excessive (eg. cancer) or inadequate (eg. coronary artery disease) neovascularization. Avascular tumors are severely restricted in their growth potential because of the lack of a blood supply. For tumors to develop in size and metastatic potential they must make an "angiogenic switch" through perturbing the local balance of proangiogenic and antiangiogenic factors. Frequently, tumors overexpress proangiogenic factors, such as vascular endothelial growth factor, allowing them to make this angiogenic switch. Two strategies used in the development of antiangiogenic agents involve the inhibition of proangiogenic factors (eg. anti-vascular endothelial growth factor monoclonal antibodies) as well as therapy with endogenous inhibitors of angiogenesis. Emerging antiangiogenic agents currently in clinical studies are discussed in this review.
- Published
- 2005
25. Treatment of associated anemia in different hematological disorders with epoetin alpha
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V, Maisnar and K, Chroust
- Subjects
Epoetin Alfa ,Male ,Treatment Outcome ,Hematologic Neoplasms ,Hematinics ,Quality of Life ,Humans ,Anemia ,Female ,Erythropoietin ,Recombinant Proteins - Abstract
The communication is summarizing results of study aimed to ascertain the efficacy of treatment with epoetin alpha in patients with different hematological disorders and, at the same time to evaluate the impact of this treatment on quality of their lives. Treatment efficacy in separate patients of the monitored population has been evaluated not only according to hemoglobin level increase, but also according to its effect on erythrocyte products consumption needed to control anemic syndrome. Overall 134 patients with different lymphoproliferative disorders were included in the evaluation. Full-extended monitoring, i.e. at least 3-month treatment with epoetin alpha, was passed by 127 (94.8%) patients. Favorable effect of epoetin alpha administration was most often reported in patients with multiple myeloma (85.7%), Waldenstrom s macroglobulinemia (80%) and chronic lymphatic leukemia (76.7%). Conversely the lowest efficacy was reported in the group of patients with myelodysplastic syndrome. Administration of epoetin alpha within treatment of underlying anemia in numerous hematological disorders represents suitable alternative to the substitution therapy via erythrocyte transfusions. Approximately 75% of monitored patients showed improvement of life quality, in some cases irrespective of results of treatment of their underlying disorder.
- Published
- 2005
26. [The treatment of multiple myeloma with an allogeneic peripheral blood stem cell transplantation using a non-myeloablative conditioning regimen]
- Author
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M, Kmonícek, L, Jebavý, M, Lánská, P, Zák, J, Malý, and V, Maisnar
- Subjects
Male ,Immunocompromised Host ,Peripheral Blood Stem Cell Transplantation ,Transplantation Conditioning ,Cytomegalovirus Infections ,Graft vs Host Disease ,Humans ,Transplantation, Homologous ,Female ,Middle Aged ,Multiple Myeloma ,Aged - Abstract
Between November 1998 and October 1999 authors treated five multiple myeloma patients with an allogeneic peripheral blood stem cell transplantation from HLA-identical sibling using a non-myeloablative conditioning regimen. The median age at the time of transplantation was 58 (range: 47-65) years. In all patients one (n = 3) or two (n = 2) autologous peripheral blood stem cell transplantations were already performed. Conditioning was performed with fludarabine, oral busulfan and anti-T-lymphocyte globulin. All patients engrafted from 13 to 18 (median: 17) days from transplantation. The duration of neutropenia (absolute neutrophiles count500/microl) and thrombocytopenia (platelets20,000/microl) ranged between 4 and 19 (median: 18) and between 13 and 18 (median: 17) days, respectively. In the period of posttransplant pancytopenia two patients developed mild gastrointestinal mucositis and two pulmonary complications (bronchopneumonia and dyspnoe of unknown etiology). Two patients had grade III-IV acute graft-versus-host disease (GvHD), none had extensive chronic GvHD. Two patients received prophylactic donor-lymphocytes infusions 200 and 225 days from transplantation. One of them developed grade III acute GvHD. All patients responded. One achieved complete and four partial remission of the disease. One patient died 111 days from transplantation due to bronchopneumonia, four are alive and well, in the stable disease, 35, 36, 51 and 52 weeks after transplantation. It can be concluded that allogenic peripheral blood stem cell transplantation using a non-myeloablative conditioning regimen is an effective way of the multiple myeloma treatment with an acceptable toxicity.
- Published
- 2005
27. [Monoclonal gammopathies in a series of 1683 plasma donors]
- Author
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M, Tichý, V, Rehácek, V, Maisnar, K, Dominiková, and V, Palicka
- Subjects
Adult ,Male ,Adolescent ,Paraproteinemias ,Humans ,Blood Donors ,Female ,Middle Aged ,Blood Protein Electrophoresis - Abstract
Monoclonal gammopathies are very heterogenic groups of disorders characterized by the proliferation of a single clone of plasma cells producing a monoclonal immunoglobulin (paraprotein). Monoclonal gammopathies (Kyle) are classified as malignant monoclonal gammopathies and monoclonal gammopathy of the undetermined significance. The prevalence of paraproteinemias is about 1% in people up to the age of 60 and about 10% in persons older than 80 years of age.We examined blood serum from 1683 plasma donors (18-60 years) by electrophoretic analysis during the period 1999-2003. We determined monoclonal immunoglobulins in 10 of them (0.6%). The presence of monoclonal gammopathies of undetermined significance was the most frequent (6x), one case was a transient monoclonal gammopathy, two patients were not examined and one patient (46 years old man) had the diagnosis of multiple myeloma. The immunoglobulin class of six paraproteins IgG were observed (4x kappa, 2x lambda), paraprotein IgA was found in two patients (1x kappa, 1x lambda), paraproteinemia IgM-kappa in one patient and double paraproteinemia IgG-kappa + IgA-kappa was proved in another one. M-gradient was determined in nine cases by screening electrophoretic analysis on the agarose gel (SEBIA, France). One M-protein (IgA-lambda) was hidden in beta-globulin region and the diagnosis of multiple myeloma was determined after clinical manifestation this disease.Our study shows, that electrophoretic analysis of serum is necessary to do in all types of blood donors (plasma, blood, thrombocytes). Reliable proof of monoclonal immunoglobulins in blood serum or urine is given only by immunofixation electrophoresis.
- Published
- 2004
28. Successful radiotherapy treatment of lacrimal gland infiltration in patient with Sjögren΄s syndrome
- Author
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R Slezak, I Sirak, S Brokesova, V Maisnar, J Petera, and H Langrova
- Subjects
Adult ,Economics and Econometrics ,medicine.medical_specialty ,medicine.medical_treatment ,Lacrimal gland ,stomatognathic system ,Materials Chemistry ,Media Technology ,medicine ,Humans ,In patient ,Diplopia ,Lacrimal Apparatus Diseases ,business.industry ,Forestry ,medicine.disease ,eye diseases ,Radiation therapy ,stomatognathic diseases ,Sjogren's Syndrome ,medicine.anatomical_structure ,Local radiotherapy ,Female ,Radiotherapy treatment ,Radiology ,Sjogren s ,medicine.symptom ,business ,Infiltration (medical) - Abstract
Objective To present a single case report on successful radiotherapy treatment of lacrimal gland infiltration in patient with Sjogren΄s syndrome. Background Radiotherapy is occasionally used for the treatment of benign disorders. There is no report on use of radiotherapy for local treatment of the Sjogren΄s syndrome in the literature. Methods Female patient with lacrimal gland involvement as a part of Sjogren΄s syndrome with diplopia and visus deterioration was treated by radiotherapy with eye shielding. Results Regression of the infiltration with full restoration of visus and minimal acute radiation reaction was achieved. Conclusion A case report of successful use of local radiotherapy in the treatment of lacrimal gland affected by Sjogren΄s syndrome is presented (Fig. 3, Ref. 6). Full Text in PDF www.elis.sk.
- Published
- 2012
- Full Text
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29. [Importance of selected laboratory indicators in the differential diagnosis and monitoring of multiple myeloma]
- Author
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V, Maisnar, M, Tousková, J, Malý, J, Krejsek, M, Kmonícek, and O, Kopecký
- Subjects
Male ,Membrane Glycoproteins ,Syndecans ,Paraproteinemias ,Middle Aged ,Neopterin ,Diagnosis, Differential ,Bone Marrow ,Biomarkers, Tumor ,Humans ,Female ,Proteoglycans ,Syndecan-1 ,Multiple Myeloma ,beta 2-Microglobulin - Abstract
Multiple myeloma is one of the most common haematologic malignancies. Currently there are numerous studies looking for new prognostic markers in multiple myeloma. The most important of them are the markers related to proliferative activity of neoplastic cells or to size of tumor mass. The subject of this paper are the results obtained from investigation of some such laboratory markers in a group of patients with monoclonal gammopathies diagnosed at our department in the last 3 years. We analyzed blood and bone marrow samples from 51 patients with new diagnosed monoclonal gammopathies, 14 of them were patients with monoclonal gammopathy of undetermined significance and 37 patients had multiple myeloma. 17 patients with multiple myeloma were treated by high-dose chemotherapy regimen. We assessed significance of selected laboratory markers for differential diagnosis of monoclonal gammopathies and for monitoring of activity of multiple myeloma. Among the investigated parameters, we verified the significance of cell cycle analysis of bone marrow plasmatic population and of the determination of the number of circulating myeloma cells in differential diagnosis of monoclonal gammopathies. In our opinion, the determination of soluble CD138, beta 2-microglobulin and neopterin serum levels can be also recommended as helpful markers for a solution of this problem. Except of beta 2-microglobulin serum level we did not find statistically significant correlation with activity of multiple myeloma in any of the investigated parameters.
- Published
- 2002
30. [Detection of multiple myeloma cells using multicolor immunofluorescence and flow cytometry]
- Author
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M, Tousková, V, Maisnar, J, Krejsek, and O, Kopecký
- Subjects
Neoplasm, Residual ,Antigens, CD ,Biomarkers, Tumor ,Fluorescent Antibody Technique ,Humans ,Flow Cytometry ,Multiple Myeloma - Abstract
The advent of new therapeutic approaches to multiple myeloma made necessary the introduction of novel methods for detection of minimal residual disease. Among others approaches residual disease can be detected by the immunofluorescence using flow cytometry. We have examined the co-expression of CD19, CD38, CD45, CD54, CD56, and CD138 molecules in cells of peripheral blood and bone marrow aspirates in patients with multiple myeloma by 3-color flow cytometry. For the detection and characterization of multiple myeloma cells, combinations of following antibodies were used: anti-CD19 FITC, anti-CD38 FITC, anti-CD38 PE, anti-CD54 FITC, anti-CD56 PE-Cy5, anti-CD45 PE, anti-CD45 PE-Cy5 (Immunotech) and anti CD138 PE (Serotec). The samples were analyzed using EPICS XL (Coulter) flow cytometer, and the analysis was based on at least 10,000 events. Samples from 17 patients were analyzed. The percentage of multiple myeloma cells ranged between 0.3% and 54.2% in bone marrow aspirates and between 0.0 and 11.8% in periferal blood. The expression of CD138, CD38, CD54 and CD56 molecules was found in 100%, 100%, 85% and 68% of examined cases, respectively. In our opinion, multiple myeloma cells are best characterized by following combinations of antibodies: CD38 FITC/CD138 PE/CD45 PE-Cy5, CD54 FITC/CD138 PE/CD56 PE-Cy5 or CD54 FITC/CD38 PE/CD 56 PE-Cy5. The identification of a malignant clone is the first and the most important step in the characterization of the disease, determination of its prognosis and the detection of residual disease after treatment. Three-color flow cytometry represents a method which can meet these goals.
- Published
- 2000
31. [Recurrent spontaneous dislocation of the catheter in a venous vascular access port system]
- Author
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P, Zák, V, Maisnar, A, Lojík, and M, Tauchman
- Subjects
Male ,Catheterization, Central Venous ,Catheters, Indwelling ,Vena Cava, Superior ,Recurrence ,Humans ,Equipment Failure ,Infusion Pumps, Implantable ,Jugular Veins ,Middle Aged - Abstract
The authors describe the problem of spontaneous changes of the position of the catheter in venous vascuports with a cannula inserted via the vena subclavia or internal jugular vein into the vena cava superior, used most frequently for repeated administration of chemotherapy. The correct position of the catheter is important in the venous port system for the proper function of the whole system. During dislocation of the catheter the function is impaired to a varying extent and the number of inflammatory and thrombotic complications increases and dislocations beyond the venous system lead to extravasal administration of the drug. Possible diagnosis of this condition and subsequent correction of the position of the cannula is described in a 48-year old man who developed spontaneous dislocation of the position of the cannula from the vena cava superior into the internal jugular vein. Correction by means of a hook inserted via the ipsilateral femoral vein into the vena cava inferior and via the vena cava superior into the internal jugular vein was successful only temporarily. Because of repeated dislocation the port system was removed.
- Published
- 1998
32. [A fully implantable port system for venous access. Personal experience with 91 patients]
- Author
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P, Zák, M, Tauchman, V, Maisnar, K, Podzimek, S, Mirová, J, Voglová, P, Dulícek, S, Filip, and L, Chrobák
- Subjects
Male ,Catheterization, Central Venous ,Catheters, Indwelling ,Time Factors ,Humans ,Female - Abstract
A fully implantable venous port system with a cannula inserted into the central venous system was implanted to 91 patients. The system was used for the administration of different types of intravenous preparations, incl. transfusions of erythrocyte mass and parenteral nutrition. With in the framework of autologous transplantation via the port system haematopoietic progenitor cells from the peripheral blood stream were administered. Part of the introduced systems was used for monitoring of the central venous overpressure and for collecting blood samples. The system was introduced on an average for 289 days, with a median of 245 days, range 82-872 days. During the implantation seven complications developed, in three instances the port was removed prematurely. During treatment 16 complications were observed, which in six instances led to early explantation of the venous port. The number of complications in total amounted to 0.87 per 1000 treatment days. The system was well tolerated by the patients because of its functional effectiveness and minimal cosmetic changes, and because it is not demanding it was also accepted well by the nursing staff.
- Published
- 1997
33. Rizikové monoklonální gamapatie nejasného významu -- léčit nebo neléčit?
- Author
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V., Maisnar and R., Hájek
- Subjects
- *
ACUTE myeloid leukemia , *LEUKEMIA , *CYTOGENETICS , *ACUTE leukemia , *CHROMOSOME abnormalities , *PATIENTS - Abstract
Monoclonal gammopathy of undetermined significance (MGUS) is defined as a clinically silent, symptom-free state that does not meet the diagnostic criteria of multiple myeloma (MM), Waldenstrom macroglobulinemia, AL-amyloidosis or any other malignant lymphoproliferative disease. Long-term follow-up has demonstrated that this may be a pre-cancerous state with transformation into a malignant monoclonal gammopathy in approximately 1% of cases annually. Probably all cases of MM arise as a transformation of MGUS. In this overview, the author attempts to answer the key question, namely whether it is currently possible in some way to prevent the transformation of MGUS into MM or to at least to slow this down. The answer in MGUS patients is currently unequivocally NO. In view of the significantly higher risk of transformation in patients with asymptomatic multiple myeloma than in patients with MGUS, further analysis by the CMG will focus on this group of patients with the goal of selecting the group at highest risk and to subject this group to early and if possible nontoxictreatment. [ABSTRACT FROM AUTHOR]
- Published
- 2013
34. Kazuistika závaŽné pancytopenie s dominující megaloblastovou anémií malnutriční etiologie.
- Author
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P., Papouček, V., Maisnar, P., BĚlohlávková, I., Fátorová, J., Malý, and V., Řeháček
- Abstract
A case of severe pancytopenia in a 20-year-old immobile retarded boy is described. The perfunctory clinical findings on admission to a regional hospital raised suspicion of aplastic anaemia of drug aetiology or acute leukaemia. On admission, the initial haemoglobin value was 26 g/l with macrocytosis (MCV 122 fl). Biochemistry examinations revealed immeasurably low levels of vitamin B12 and folate. Elevated LDH and the low reticulocyte count also indicated a diagnosis of impaired erythropoiesis. The bone marrow showed significant hyperplasia of erythropoiesis with signs of megaloblastic transformation. Insufficient intake of food by the patient of low intellect was the cause of this condition. Rapid correction of the blood count occurred following nutritional support with vitamin substitution. Key words: pancytopenia, megaloblastic anaemia, malnutrition [ABSTRACT FROM AUTHOR]
- Published
- 2011
35. [Treatment of severely depressed hematopoiesis]
- Author
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M, Bláha, V, Maisnar, L, Jebavý, J, Malý, and O, Siroký
- Subjects
Adult ,Aged, 80 and over ,Male ,Adolescent ,Anemia, Aplastic ,Humans ,Female ,Middle Aged ,Child ,Aged - Abstract
Severe inhibition of haematopoiesis is a serious disease from the prognostic aspect. The authors evaluated a group of 26 patients of whom one survived for more than five years. The mean life span is 154 days. The most frequent cause of death are infectious complications, in particular septicaemia. Investigation of the aetiology of the disease was negative in 46% of the cases, in the remainder drugs were suspected most frequently, in particular antibiotics. It is very important to prevent the development of secondary inhibition of haematopoiesis, in particular by careful indication of myelotoxic drugs. In case of necessity, these drugs should be administered for a short time, in the lowest effective doses with check-ups of the haemogram. Hope for affected patients in future is transplantation of bone marrow and the early administration of antilymphocytic globulin.
- Published
- 1989
36. [Granulocyte transfusion therapy]
- Author
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M, Bláha, L, Jebavý, J, Vanásek, V, Maisnar, J, Malý, M, Pecka, and O, Siroký
- Subjects
Adult ,Male ,Adolescent ,Humans ,Blood Transfusion ,Female ,Middle Aged ,Infections ,Agranulocytosis ,Granulocytes - Published
- 1987
37. Real-World Evidence on Prognostic Value of MRD in Multiple Myeloma Using Flow Cytometry.
- Author
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Muronova L, Soucek O, Zihala D, Sevcikova T, Popkova T, Plonkova H, Venglar O, Pour L, Stork M, Rihova L, Bezdekova R, Minarik J, Látal V, Novak M, Jungova A, Dekojova T, Straub J, Spacek M, Rezacova V, Maisnar V, Radocha J, Hajek R, and Jelinek T
- Subjects
- Humans, Prognosis, Female, Male, Middle Aged, Aged, Retrospective Studies, Adult, Hematopoietic Stem Cell Transplantation methods, Transplantation, Autologous, Treatment Outcome, Neoplasm Staging, Lenalidomide administration & dosage, Lenalidomide therapeutic use, Multiple Myeloma diagnosis, Multiple Myeloma mortality, Multiple Myeloma therapy, Multiple Myeloma pathology, Neoplasm, Residual diagnosis, Flow Cytometry methods
- Abstract
Minimal residual disease (MRD) is one of the most important prognostic factors in multiple myeloma (MM) and a valid surrogate for progression-free survival (PFS) and overall survival (OS). Recently, MRD negativity was approved as an early clinical endpoint for accelerated drug approval in MM. Nevertheless, there is limited evidence of MRD utility in real-world setting. In this retrospective multicenter study, we report outcomes of 331 newly diagnosed MM patients with MRD evaluation at Day+100 after autologous stem cell transplantation using flow cytometry with a median limit of detection of 0.001%. MRD negativity was reached in 47% of patients and was associated with significantly prolonged median PFS (49.2 months vs. 18.4 months; hazard ratios (HR) = 0.37; p < 0.001) and OS (not reached vs. 74.9 months; HR = 0.50; p = 0.007). Achieving MRD negativity was associated with PFS improvements regardless of age, International Staging System (ISS) stage, lactate dedydrogenase (LDH) level, or cytogenetic risk. Importantly, MRD positive patients benefited from lenalidomide maintenance versus no maintenance (18-months PFS: 81% vs. 46%; HR = 0.24; p = 0.002) while in MRD negative patients such benefit was not observed (p = 0.747). The outcomes of our real-world study recapitulate results from clinical trials including meta-analyses and support the idea that MRD positive patients profit more from lenalidomide maintenance than MRD negative ones., (© 2024 The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.)
- Published
- 2025
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- View/download PDF
38. ANCHOR: melflufen plus dexamethasone and daratumumab or bortezomib in relapsed/refractory multiple myeloma: final results of a phase I/IIa study.
- Author
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Ocio EM, Efebera YA, Hájek R, Straub J, Maisnar V, Eveillard JR, Karlin L, Mateos MV, Oriol A, Ribrag V, Richardson PG, Norin S, Obermüller J, Bakker NA, and Pour L
- Subjects
- Humans, Bortezomib therapeutic use, Dexamethasone therapeutic use, Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antibodies, Monoclonal, Melphalan analogs & derivatives, Multiple Myeloma diagnosis, Multiple Myeloma drug therapy, Neoplasms, Plasma Cell, Neutropenia chemically induced, Phenylalanine analogs & derivatives, Thrombocytopenia
- Abstract
Melphalan flufenamide (melflufen), a first-in-class, alkylating peptide-drug conjugate, demonstrated clinical benefit in combination with dexamethasone in triple-class refractory multiple myeloma (MM). The phase I/IIa ANCHOR study evaluated melflufen (30 or 40 mg) and dexamethasone (40 mg with daratumumab; 20 mg followed by 40 mg with bortezomib; dose reduced if aged ≥75 years) in triplet combination with daratumumab (16 mg/kg; daratumumab arm) or bortezomib (1.3 mg/m2; bortezomib arm) in patients with relapsed/refractory MM refractory to an immunomodulatory agent and/or a proteasome inhibitor and who had received one to four prior lines of therapy. Primary objectives were to determine the optimal dose of melflufen in triplet combination (phase I) and overall response rate (phase IIa). In total, 33 patients were treated in the daratumumab arm and 23 patients received therapy in the bortezomib arm. No dose-limiting toxicities were reported at either melflufen dose level with either combination. With both triplet regimens, the most common grade ≥3 treatment-emergent adverse events were thrombocytopenia and neutropenia; thrombocytopenia was the most common treatment-emergent adverse event leading to treatment discontinuation. In the daratumumab arm, patients receiving melflufen 30 mg remained on treatment longer than those receiving the 40-mg dose. In the daratumumab arm, the overall response rate was 73% and median progression-free survival was 12.9 months. Notably, in the bortezomib arm, the overall response rate was 78% and median progression-free survival was 14.7 months. Considering the totality of the data, melflufen 30 mg was established as the recommended dose for use with dexamethasone and daratumumab or bortezomib for future studies in relapsed/refractory MM.
- Published
- 2024
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39. Efficacy and safety of melflufen plus daratumumab and dexamethasone in relapsed/refractory multiple myeloma: results from the randomized, open-label, phase III LIGHTHOUSE study.
- Author
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Pour L, Szarejko M, Bila J, Schjesvold FH, Spicka I, Maisnar V, Jurczyszyn A, Grudeva-Popova Z, Hájek R, Usenko G, Thuresson M, Norin S, Jarefors S, Bakker NA, Richardson PG, and Mateos MV
- Subjects
- Humans, Dexamethasone therapeutic use, Proteasome Inhibitors, Transplantation, Autologous, United States, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antibodies, Monoclonal, Hematopoietic Stem Cell Transplantation, Melphalan analogs & derivatives, Multiple Myeloma diagnosis, Multiple Myeloma drug therapy, Neoplasms, Plasma Cell, Neutropenia, Phenylalanine analogs & derivatives
- Abstract
Melphalan flufenamide (melflufen), a first-in-class alkylating peptide-drug conjugate, plus dexamethasone was approved in Europe for use in patients with triple-class refractory relapsed/refractory multiple myeloma (RRMM) with ≥3 prior lines of therapy and without prior autologous stem cell transplantation (ASCT) or with a time to progression >36 months after prior ASCT. The randomized LIGHTHOUSE study (NCT04649060) assessed melflufen plus daratumumab and dexamethasone (melflufen group) versus daratumumab in patients with RRMM with disease refractory to an immunomodulatory agent and a proteasome inhibitor or who had received ≥3 prior lines of therapy including an immunomodulatory agent and a proteasome inhibitor. A partial clinical hold issued by the US Food and Drug Administration for all melflufen studies led to financial constraints and premature study closure on February 23rd 2022 (data cut-off date). In total, 54 of 240 planned patients were randomized (melflufen group, N=27; daratumumab group, N=27). Median progression-free survival (PFS) was not reached in the melflufen group versus 4.9 months in the daratumumab group (Hazard Ratio: 0.18 [95% Confidence Interval, 0.05-0.65]; P=0.0032) at a median follow-up time of 7.1 and 6.6 months, respectively. Overall response rate (ORR) was 59% in the melflufen group versus 30% in the daratumumab group (P=0.0300). The most common grade ≥3 treatment-emergent adverse events in the melflufen group versus daratumumab group were neutropenia (50% vs. 12%), thrombocytopenia (50% vs. 8%), and anemia (32% vs. 19%). Melflufen plus daratumumab and dexamethasone demonstrated superior PFS and ORR versus daratumumab in RRMM and a safety profile comparable to previously published melflufen studies.
- Published
- 2024
- Full Text
- View/download PDF
40. Clinical characteristics and outcomes in risk-stratified patients with smoldering multiple myeloma: data from the Czech Republic Registry of Monoclonal Gammopathies.
- Author
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Sandecka V, Popkova T, Stork M, Maisnar V, Minarik J, Jungova A, Pavlicek P, Stejskal L, Pospisilova L, Heindorfer A, Obernauerova J, Gregora E, Sykora M, Ullrychova J, Wrobel M, Kessler P, Jelinek T, Kunovszki P, Bathija S, Gros B, Wilbertz S, Cai Q, Lam A, and Spicka I
- Subjects
- Humans, Czech Republic epidemiology, Progression-Free Survival, Registries, Smoldering Multiple Myeloma diagnosis, Smoldering Multiple Myeloma epidemiology, Smoldering Multiple Myeloma therapy, Multiple Myeloma diagnosis, Multiple Myeloma epidemiology, Multiple Myeloma therapy
- Abstract
Smoldering multiple myeloma (SMM) is an asymptomatic precursor to active multiple myeloma (MM). The aim of this study was to report clinical characteristics and outcomes of patients with SMM stratified based on their risk of progression to MM using the Mayo 20/2/20 criteria. Data were leveraged from the Czech Myeloma Group Registry of Monoclonal Gammopathies (RMG). Key outcomes included progression-free survival from SMM diagnosis to active MM diagnosis or death (PFS), progression-free survival from SMM diagnosis to progression on first line (1 L) MM treatment or death (PFS2), and overall survival (OS). Of 498 patients, 174 (34.9%) were classified as high risk and 324 (65.1%) as non-high risk. Median follow-up was approximately 65 months. During follow-up, more patients in the high-risk vs non-high-risk group received 1 L MM treatment (76.4% vs 46.6%, p < 0.001). PFS, PFS2, and OS were significantly shorter in high-risk vs non-high-risk patients (13.2 vs 56.6 months, p < 0.001; 49.9 vs 84.9 months, p < 0.001; 93.2 vs 131.1 months, p = 0.012, respectively). The results of this study add to the growing body of evidence that patients with high-risk vs non-high-risk SMM have significantly worse outcomes, including OS., (© 2023. Springer Nature Limited.)
- Published
- 2023
- Full Text
- View/download PDF
41. Definition and Clinical Significance of the Monoclonal Gammopathy of Undetermined Significance-Like Phenotype in Patients With Monoclonal Gammopathies.
- Author
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Burgos L, Tamariz-Amador LE, Puig N, Cedena MT, Guerrero C, Jelínek T, Johnson S, Milani P, Cordon L, Perez JJ, Lasa M, Termini R, Oriol A, Hernandez MT, Palomera L, Martinez-Martinez R, de la Rubia J, de Arriba F, Rios R, Gonzalez ME, Gironella M, Cabañas V, Casanova M, Krsnik I, Perez-Montaña A, González-Calle V, Rodriguez-Otero P, Maisnar V, Hajek R, Van Rhee F, Jimenez-Zepeda V, Palladini G, Merlini G, Orfao A, de la Cruz J, Martinez-Lopez J, Lahuerta JJ, Rosiñol L, Blade J, Mateos MV, San-Miguel JF, and Paiva B
- Subjects
- Humans, Clinical Relevance, Disease Progression, Phenotype, Monoclonal Gammopathy of Undetermined Significance diagnosis, Monoclonal Gammopathy of Undetermined Significance therapy, Immunoglobulin Light-chain Amyloidosis, Paraproteinemias diagnosis, Paraproteinemias therapy, Multiple Myeloma diagnosis
- Abstract
Purpose: The existence of patients with multiple myeloma (MM) and light-chain (AL) amyloidosis who present with a monoclonal gammopathy of undetermined significance (MGUS)-like phenotype has been hypothesized, but methods to identify this subgroup are not standardized and its clinical significance is not properly validated., Patients and Methods: An algorithm to identify patients having MGUS-like phenotype was developed on the basis of the percentages of total bone marrow (BM) plasma cells (PC) and of clonal PC within the BM PC compartment, determined at diagnosis using flow cytometry in 548 patients with MGUS and 2,011 patients with active MM. The clinical significance of the algorithm was tested and validated in 488 patients with smoldering MM, 3,870 patients with active MM and 211 patients with AL amyloidosis., Results: Patients with smoldering MM with MGUS-like phenotype showed significantly lower rates of disease progression (4.5% and 0% at 2 years in two independent series). There were no statistically significant differences in time to progression between treatment versus observation in these patients. In active newly diagnosed MM, MGUS-like phenotype retained independent prognostic value in multivariate analyses of progression-free survival (PFS; hazard ratio [HR], 0.49; P = .001) and overall survival (OS; HR, 0.56; P = .039), together with International Staging System, lactate dehydrogenase, cytogenetic risk, transplant eligibility, and complete remission status. Transplant-eligible patients with active MM with MGUS-like phenotype showed PFS and OS rates at 5 years of 79% and 96%, respectively. In this subgroup, there were no differences in PFS and OS according to complete remission and measurable residual disease status. Application of the algorithm in two independent series of patients with AL predicted for different survival., Conclusion: We developed an open-access algorithm for the identification of MGUS-like patients with distinct clinical outcomes. This phenotypic classification could become part of the diagnostic workup of MM and AL amyloidosis.
- Published
- 2023
- Full Text
- View/download PDF
42. Daratumumab with lenalidomide and dexamethasone in relapsed or refractory multiple myeloma patients - real world evidence analysis.
- Author
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Stork M, Spicka I, Radocha J, Minarik J, Jelinek T, Jungova A, Pavlicek P, Pospisilova L, Sedlak F, Straub J, Pika T, Knechtova Z, Fidrichova A, Boichuk I, Sevcikova S, Maisnar V, Hajek R, and Pour L
- Subjects
- Humans, Lenalidomide therapeutic use, Dexamethasone adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Multiple Myeloma diagnosis, Multiple Myeloma drug therapy
- Abstract
We performed real world evidence (RWE) analysis of daratumumab, lenalidomide and dexamethasone (Dara-Rd) versus lenalidomide and dexamethasone (Rd) treatment in relapsed/refractory multiple myeloma patients (RRMM). In total, 240 RRMM patients were treated with Dara-Rd from 2016 to 2022 outside of clinical trials in all major Czech hematology centers. As a reference, 531 RRMM patients treated with Rd were evaluated. Patients' data were recorded in the Czech Registry of Monoclonal Gammopathies (RMG). Partial response (PR) or better response (ORR) was achieved in significantly more patients in Dara-Rd than in Rd group (91.2% vs. 69.9%; p < 0.001). The median progression free survival (PFS) was 26.9 months in the Dara-Rd and 12.8 months in the Rd group (p < 0.001). Median overall survival (OS) was not reached in the Dara-Rd compared to 27.2 months in the Rd group (p = 0.023). In patients with 1-3 previous treatment lines, there was significant PFS benefit of Dara-Rd compared to Rd (median PFS not reached vs. 13.2 months; p < 0.001). In patients with > 3 previous treatment lines, there was no significant PFS benefit of Dara-Rd treatment (7.8 months vs. 9.9 months; p = 0.874), similarly in patients refractory to PI + IMIDs (11.5 months vs. 9.2 months; p = 0.376). In RWE conditions, the median PFS in RRMM patients treated with Dara-Rd is shorter when compared to clinical trials. In heavily pretreated RRMM patients, efficacy of Dara-Rd treatment is limited; best possible outcomes of Dara-Rd are achieved in minimally pretreated patients., (© 2023. The Author(s).)
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- 2023
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43. Patient Characteristics, Treatment Patterns, and Outcomes in Triple-Class Exposed Relapsed/Refractory Multiple Myeloma Patients, a Retrospective Observational Study Using Czech Registry Data.
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Maisnar V, Pour L, Spicka I, Jelinek T, Minarik J, Jungova A, Stork M, Straub J, Radocha J, Pika T, Pospisilova L, Nair S, Kunovszki P, and Hajek R
- Subjects
- Humans, Czech Republic epidemiology, Progression-Free Survival, Retrospective Studies, Registries, Multiple Myeloma drug therapy
- Abstract
Background: Although novel therapies improved prognosis of multiple myeloma (MM) patients, clinical outcomes in the multi-refractory population are still poor., Patients and Methods: We reviewed data from the Czech Registry of Monoclonal Gammopathies, identified and characterized triple-class exposed (3CE) relapsed/refractory MM patients, treatment patterns after 3CE, assessed overall survival (OS), progression-free survival (PFS), time to next treatment (TTNT), explored cohorts with and without triple- and penta-refractoriness., Results: In 83 3CE patients who started subsequent therapies, the median OS was 14.2 months (95% CI, 8.5-19.9), PFS 6.2 months (95% CI, 3.9-8.5), and TTNT 7.2 months (95% CI, 4.6-9.8). Triple- and penta-class refractory patients had a significantly worse prognosis in all outcomes. Their life expectancy was shorter, the disease progression started earlier, and the TTNT was shorter, which increased likelihood of becoming refractory to more therapies. Time-to-event results from the first index date and all index dates analyses were very similar., Conclusion: Similar to previous studies from the US and Europe, our results show a high disease burden. Introduction of novel therapies, such as CAR-T cells, new bispecific and trispecific monoclonal antibodies, and other drugs, is expected to bring significant benefits to these patients., (Copyright © 2022. Published by Elsevier Inc.)
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- 2023
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44. Real-world evidence of efficacy and safety of pomalidomide and dexamethasone in relapsed/refractory multiple myeloma patients: Czech registry data.
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Sandecka V, Pour L, Špička I, Minařík J, Radocha J, Jelínek T, Pavlíček P, Jungová A, Kessler P, Wróbel M, Štork M, Štraub J, Pika T, Čápková L, Ševčíková S, Maisnar V, and Hájek R
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- Humans, Czech Republic epidemiology, Dexamethasone therapeutic use, Routinely Collected Health Data, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Multiple Myeloma drug therapy
- Abstract
We assessed the outcomes of pomalidomide and dexamethasone treatment in relapsed/refractory multiple myeloma (RRMM) patients with ≥1 prior line of therapy. We analyzed the data of all RRMM patients treated with pomalidomide and dexamethasone at nine Czech centers between 2013 and 2018. The source of the data was the Registry of Monoclonal Gammopathies of the Czech Republic. Primary endpoints included response rates based on International Myeloma Working Group criteria and survival measures, including progression-free survival (PFS) and overall survival (OS). Secondary endpoints were toxicities and previous treatment patterns, including refractory to lenalidomide, and their impact on final outcomes. The overall response rate was 51.8% and the clinical benefit rate (including patients with minimal response) was 67.1%, with 0.6% of complete responses, 8.5% of very good partial responses, and 42.1% of partial responses (PR). Overall, 16.5% of patients had a minimal response, and 32.3% had stable disease /progression. Median PFS was 8.8 months and the median OS was 14.2 months. In patients who achieved ≥PR, the median PFS and OS were significantly longer compared to non-responders (median PFS (12.1 vs. 4.5 months, p≤0.001 respectively), median OS (22.1 vs. 7.7 months, p≤0.001, respectively). The most frequent adverse events (AEs) were neutropenia (29.9%) and anemia (18.9%), non-hematological AEs included infections (14.6%) and fatigue (7.3%). Our analysis confirmed the effectiveness of pomalidomide and dexamethasone in a real-world setting. This therapy achieved reasonable outcomes comparable to the data from clinical trials even though this was an unbiased cohort of patients.
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- 2022
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45. Ixazomib, Lenalidomide and Dexamethasone in Relapsed and Refractory Multiple Myeloma in Routine Clinical Practice: Extended Follow-Up Analysis and the Results of Subsequent Therapy.
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Minarik J, Radocha J, Jungova A, Straub J, Jelinek T, Pika T, Pour L, Pavlicek P, Harvanova L, Pospisilova L, Krhovska P, Novakova D, Jindra P, Spicka I, Plonkova H, Stork M, Bacovsky J, Maisnar V, and Hajek R
- Abstract
Background: We confirmed the benefit of addition of ixazomib to lenalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma (RRMM) in unselected real-world population. We report the final analysis for overall survival (OS), second progression free survival (PFS-2), and the subanalysis of the outcomes in lenalidomide (LEN) pretreated and LEN refractory patients., Methods: We assessed 344 patients with RRMM, treated with IRD (N = 127) or RD (N = 217). The data were acquired from the Czech Registry of Monoclonal Gammopathies (RMG). With prolonged follow-up (median 28.5 months), we determined the new primary endpoints OS, PFS and PFS-2. Secondary endpoints included the next therapeutic approach and the survival measures in LEN pretreated and LEN refractory patients., Results: The final overall response rate (ORR) was 73.0% in the IRD cohort and 66.8% in the RD cohort. The difference in patients reaching ≥VGPR remained significant (38.1% vs. 26.3%, p = 0.028). Median PFS maintained significant improvement in the IRD cohort (17.5 vs. 12.5 months, p = 0.013) with better outcomes in patients with 1-3 prior relapses (22.3 vs. 12.7 months p = 0.003). In the whole cohort, median OS was for IRD vs. RD patients 40.9 vs. 27.1 months ( p = 0.001), with further improvement within relapse 1-3 (51.7 vs. 27.8 months, p ˂ 0.001). The median PFS of LEN pretreated (N = 22) vs. LEN naive (N = 105) patients treated by IRD was 8.7 vs. 23.1 months ( p = 0.001), and median OS was 13.2 vs. 51.7 months ( p = 0.030). Most patients in both arms progressed and received further myeloma-specific therapy (63.0% in the IRD group and 53.9% in the RD group). Majority of patients received pomalidomide-based therapy or bortezomib based therapy. Significantly more patients with previous IRD vs. RD received subsequent monoclonal antibodies (daratumumab-16.3% vs. 4.3%, p = 0.0054; isatuximab 5.0% vs. 0.0%, p = 0.026) and carfilzomib (12.5 vs. 1.7%, p = 0.004). The median PFS-2 (progression free survival from the start of IRD/RD therapy until the second disease progression or death) was significantly longer in the IRD cohort (29.8 vs. 21.6 months, p = 0.016). There were no additional safety concerns in the extended follow-up., Conclusions: The IRD regimen is well tolerated, easy to administer, and with very good therapeutic outcomes. The survival measures in unsorted real-world population are comparable to the outcomes of the clinical trial. As expected, patients with LEN reatment have poorer outcomes than those who are LEN-naive. The PFS benefit of IRD vs. RD translated into significantly better PFS-2 and OS, but the outcomes must be accounted for imbalances in pretreatment group characteristics (especially younger age and stem cell transplant pretreatment), and in subsequent therapies.
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- 2022
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46. Unexpected Heterogeneity of Newly Diagnosed Multiple Myeloma Patients with Plasmacytomas.
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Stork M, Sevcikova S, Jelinek T, Minarik J, Radocha J, Pika T, Pospisilova L, Spicka I, Straub J, Pavlicek P, Jungova A, Knechtova Z, Sandecka V, Maisnar V, Hajek R, and Pour L
- Abstract
In multiple myeloma (MM), malignant plasma cells infiltrate the bone marrow. In some cases, plasma cells migrate out of the bone marrow creating either para-skeletal plasmacytomas (PS) or infiltrating soft tissues as extramedullary plasmacytomas (EMD). The aim of this study was to define risk groups in newly diagnosed MM (NDMM) patients with PS and EMD plasmacytomas. In total, 523 NDMM patients with PS plasmacytomas and 196 NDMM patients with EMD plasmacytomas were diagnosed in the Czech Republic between 2004 and 2021 using modern imaging methods. Patients’ data were analyzed from the Registry of Monoclonal Gammopathies of the Czech Myeloma Group. In NDMM patients with PS plasmacytomas, we found a subgroup with <5% of bone-marrow plasma cells to have the best prognosis (mPFS: 58.3 months (95% CI: 33.0−NA); mOS: not reached). The subgroup with >5% of bone-marrow plasma cells and ≥3 plasmacytomas had the worst prognosis (mPFS: 19.3 months (95% CI: 13.4−28.8), p < 0.001; mOS: 27.9 months (95% CI: 19.3−67.8), p < 0.001). Our results show association between tumor burden and prognosis of NDMM patients with plasmacytomas. In the case of PS plasmacytomas, NDMM patients with low BM PC infiltration have an excellent prognosis.
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- 2022
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47. Identification of patients at high risk of secondary extramedullary multiple myeloma development.
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Stork M, Sevcikova S, Minarik J, Krhovska P, Radocha J, Pospisilova L, Brozova L, Jarkovsky J, Spicka I, Straub J, Pavlicek P, Jungova A, Jelinek T, Sandecka V, Maisnar V, Hajek R, and Pour L
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- Aged, Female, Humans, Male, Multiple Myeloma mortality, Prognosis, Retrospective Studies, Risk Factors, Survival Analysis, Multiple Myeloma physiopathology
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Multiple myeloma (MM) is characterized by malignant plasma cell infiltration of the bone marrow. In extramedullary multiple myeloma (EMD), a subclone of these cells migrates out of the bone marrow. Out of 4 985 MM patients diagnosed between 2005 and 2017 in the Czech Republic, we analyzed 234 secondary EMD patients to clarify risk factors of secondary EMD development. We found younger age [<65 years; odds ratio (OR) 4·38, 95% confidence interval (CI): 2·46-7·80, P < 0·0001], high lactate dehydrogenase (LDH) levels (>5 μkat/l; OR 2·07, 95% CI: 1·51-2·84, P < 0·0001), extensive osteolytic activity (OR 2·21, 95% CI: 1·54-3·15, P < 0·001), and immunoglobulin A (IgA; OR 1·53, 95% CI: 1·11-2·11, P = 0·009) or the non-secretory type of MM (OR 2·83; 95% CI: 1·32-6·04, P = 0·007) at the time of MM diagnosis to be the main risk factors for secondary EMD development. Newly diagnosed MM (NDMM) patients with subsequent EMD had inferior median progression-free (PFS) and overall (OS) survival when compared to NDMM patients without future EMD [mPFS: 13·8 months (95% CI: 11·4-16·3) vs 18·8 months (95% CI: 17·7-19·9), P = 0·006; mOS: 26·7 months (95% CI: 18·1-35·4) vs 58·7 months (95% CI: 54·8-62·6), P < 0·001]. We found that NDMM patients with specific risk factors associated with secondary EMD development have a more aggressive disease course before secondary EMD develops., (© 2021 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)
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- 2022
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48. Melflufen or pomalidomide plus dexamethasone for patients with multiple myeloma refractory to lenalidomide (OCEAN): a randomised, head-to-head, open-label, phase 3 study.
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Schjesvold FH, Dimopoulos MA, Delimpasi S, Robak P, Coriu D, Legiec W, Pour L, Špička I, Masszi T, Doronin V, Minarik J, Salogub G, Alekseeva Y, Lazzaro A, Maisnar V, Mikala G, Rosiñol L, Liberati AM, Symeonidis A, Moody V, Thuresson M, Byrne C, Harmenberg J, Bakker NA, Hájek R, Mateos MV, Richardson PG, and Sonneveld P
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- Aged, Dexamethasone adverse effects, Female, Humans, Lenalidomide adverse effects, Male, Melphalan adverse effects, Melphalan analogs & derivatives, Middle Aged, Phenylalanine adverse effects, Phenylalanine analogs & derivatives, SARS-CoV-2, Thalidomide adverse effects, Thalidomide analogs & derivatives, COVID-19 Drug Treatment, Antineoplastic Combined Chemotherapy Protocols adverse effects, Multiple Myeloma drug therapy
- Abstract
Background: Melphalan flufenamide (melflufen), an alkylating peptide-drug conjugate, plus dexamethasone showed clinical activity and manageable safety in the phase 2 HORIZON study. We aimed to determine whether melflufen plus dexamethasone would provide a progression-free survival benefit compared with pomalidomide plus dexamethasone in patients with previously treated multiple myeloma., Methods: In this randomised, open-label, head-to-head, phase 3 study (OCEAN), adult patients (aged ≥18 years) were recruited from 108 university hospitals, specialist hospitals, and community-based centres in 21 countries across Europe, North America, and Asia. Eligible patients had an ECOG performance status of 0-2; must have had relapsed or refractory multiple myeloma, refractory to lenalidomide (within 18 months of randomisation) and to the last line of therapy; and have received two to four previous lines of therapy (including lenalidomide and a proteasome inhibitor). Patients were randomly assigned (1:1), stratified by age, number of previous lines of therapy, and International Staging System score, to either 28-day cycles of melflufen and dexamethasone (melflufen group) or pomalidomide and dexamethasone (pomalidomide group). All patients received dexamethasone 40 mg orally on days 1, 8, 15, and 22 of each cycle. In the melflufen group, patients received melflufen 40 mg intravenously over 30 min on day 1 of each cycle and in the pomalidomide group, patients received pomalidomide 4 mg orally daily on days 1 to 21 of each cycle. The primary endpoint was progression-free survival assessed by an independent review committee in the intention-to-treat (ITT) population. Safety was assessed in patients who received at least one dose of study medication. This study is registered with ClinicalTrials.gov, NCT03151811, and is ongoing., Findings: Between June 12, 2017, and Sept 3, 2020, 246 patients were randomly assigned to the melflufen group (median age 68 years [IQR 60-72]; 107 [43%] were female) and 249 to the pomalidomide group (median age 68 years [IQR 61-72]; 109 [44%] were female). 474 patients received at least one dose of study drug (melflufen group n=228; pomalidomide group n=246; safety population). Data cutoff was Feb 3, 2021. Median progression-free survival was 6·8 months (95% CI 5·0-8·5; 165 [67%] of 246 patients had an event) in the melflufen group and 4·9 months (4·2-5·7; 190 [76%] of 249 patients had an event) in the pomalidomide group (hazard ratio [HR] 0·79, [95% CI 0·64-0·98]; p=0·032), at a median follow-up of 15·5 months (IQR 9·4-22·8) in the melflufen group and 16·3 months (10·1-23·2) in the pomalidomide group. Median overall survival was 19·8 months (95% CI 15·1-25·6) at a median follow-up of 19·8 months (IQR 12·0-25·0) in the melflufen group and 25·0 months (95% CI 18·1-31·9) in the pomalidomide group at a median follow-up of 18·6 months (IQR 11·8-23·7; HR 1·10 [95% CI 0·85-1·44]; p=0·47). The most common grade 3 or 4 treatment-emergent adverse events were thrombocytopenia (143 [63%] of 228 in the melflufen group vs 26 [11%] of 246 in the pomalidomide group), neutropenia (123 [54%] vs 102 [41%]), and anaemia (97 [43%] vs 44 [18%]). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]). 27 [12%] patients in the melflufen group and 32 [13%] in the pomalidomide group had fatal treatment-emergent adverse events. Fatal treatment-emergent adverse events were considered possibly treatment related in two patients in the melflufen group (one with acute myeloid leukaemia, one with pancytopenia and acute cardiac failure) and four patients in the pomalidomide group (two patients with pneumonia, one with myelodysplastic syndromes, one with COVID-19 pneumonia)., Interpretation: Melflufen plus dexamethasone showed superior progression-free survival than pomalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma., Funding: Oncopeptides AB., Competing Interests: Declaration of interests FHS reports institutional grant support from Celgene, GlaxoSmithKline, Janssen, Oncopeptides AB, and Sanofi; payment or honoraria (personal) from Amgen, Bristol Myers Squibb, Celgene, Janssen, Novartis, Oncopeptides AB, Schain, Skylite DX, and Takeda; advisory board or safety monitoring board participation for AbbVie, Amgen, Celgene, Janssen, Novartis, and Oncopeptides AB; and stock or stock options from Nordic Nanovector and Oncopeptides AB outside of the submitted work. M-AD reports payment or honoraria from Amgen, BeiGene, Bristol Myers Squibb, Janssen, and Takeda outside of the submitted work. SD reports payment or honoraria from Amgen, Janssen, and Takeda outside of the submitted work. DC reports consulting fees from Amgen and Janssen, payment or honoraria from Amgen and Novartis, support for meetings or travel from Amgen and Janssen, and advisory board or safety monitoring board participation for Amgen, Janssen, and Novartis outside of the submitted work. IS reports consulting fees from Amgen, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Janssen-Cilag, Novartis, Sanofi, PharmaMar, and Takeda; payment or honoraria from Amgen, Bristol Myers Squibb, Celgene, Janssen-Cilag, Sanofi, and Takeda; support for meetings or travel from Amgen, Bristol Myers Squibb, Celgene, and Janssen-Cilag; and advisory board or safety monitoring board participation for Amgen, Bristol Myers Squibb, Celgene, GlaxoSmithKine, Janssen-Cilag, PharmaMar, Sanofi, and Takeda outside of the submitted work. TM reports advisory board participation from AbbVie, Bristol Myers Squibb, Janssen-Cilag, Novartis, Pfizer, and Takeda outside of the submitted work. JM reports consulting fees (personal) from Amgen, Bristol Myers Squibb, Celgene, Janssen, Sanofi, and Takeda; payment or honoraria from Bristol Myers Squibb, Celgene, Janssen, Sanofi, and Takeda; support for meetings or travel from Bristol Myers Squibb, Janssen, and Takeda; and safety monitoring board participation for Oncopeptides AB outside of the submitted work. VM reports consulting fees from Amgen, Bristol Myers Squibb/Celgene, Janssen, and Takeda; payment or honoraria from Amgen, Bristol Myers Squibb/Celgene, Janssen, Takeda, and The Binding Site; support for meetings or travel from Amgen, Bristol Myers Squibb/Celgene, Janssen, and Takeda; and advisory board or safety monitoring board participation for Amgen, Bristol Myers Squibb/Celgene, Janssen, and Takeda outside of the submitted work. GM reports payment or honoraria from AbbVie, Amgen, Celgene, Janssen, Krka, Novartis, Sandoz, and Takeda, and support for meetings or travel from AbbVie, Celgene, Janssen, and Takeda outside of the submitted work. LR reports payment or honoraria from Amgen, Celgene, GlaxoSmithKline, Janssen, Sanofi, and Takeda, and advisory board or safety monitoring board participation for Amgen, Celgene, GlaxoSmithKline, Janssen, Sanofi, and Takeda outside of the submitted work. AML reports institutional grant support from AbbVie, Archigen, BeiGene, Celgene, Fibrogen, GlaxoSmithKline, Incyte, Janssen, Karyopharm, Morphosys, Novartis, Onconova, Oncopeptides AB, Pfizer, Roche, Sanofi, Servier, Takeda, and Verastem; consulting fees (personal) from Incyte; payment or honoraria from AbbVie, Bristol Myers Squibb, Celgene, IQVIA, Janssen, and Servier; support for travel from AbbVie, Bristol Myers Squibb, Celgene, IQVIA, Janssen, Novartis, Roche, Sanofi, Takeda, and Verastem; and advisory board or safety monitoring board participation for Amgen and Servier outside of the submitted work. AS reports institutional grant support from AbbVie, Amgen, Astellas, Bristol Myers Squibb, Gilead, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, and Takeda; payment or honoraria from AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Gilead, Janssen, Novartis, Pfizer, Roche, Sanofi, and Takeda; and support for meetings or travel from AbbVie, Bristol Myers Squibb, Gilead, Janssen, Novartis, Pfizer, Roche, and Sanofi outside of the submitted work. VM and NAB report employment at Oncopeptides AB and stock or stock options from Oncopeptides AB outside of the submitted work. MT is an employee of Statisticon, for which Oncopeptides is a client, and owns stock options in Oncopeptides. CB reports employment at Oncopeptides AB, grants or contracts from Takeda, and stock options at Oncopeptides AB outside of the submitted work. JH reports consulting fees from Oncopeptides AB and stock or stock options from Oncopeptides AB outside of the submitted work. RH reports institutional grants or contracts from Amgen, Bristol Myers Squibb, Celgene, Janssen, Novartis, and Takeda; consulting fees (personal) from AbbVie, Amgen, Bristol Myers Squibb, Celgene, Janssen, Novartis, PharmaMar, and Takeda; payment or honoraria from Amgen, Bristol Myers Squibb, Celgene, Janssen, PharmaMar, and Takeda; support for meetings or travel from Amgen, Celgene, Janssen, and Takeda; advisory board or safety monitoring board participation for Amgen, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Oncopeptides AB, Sanofi, and Takeda outside of the submitted work. M-VM reports payment or honoraria from Amgen, Bristol Myers Squibb/Celgene, GlaxoSmithKline, Janssen, Pfizer, and Sanofi, and advisory board or safety monitoring board participation for Amgen, bluebird bio, Bristol Myers Squibb/Celgene, GlaxoSmithKline, Janssen, Oncopeptides AB, Pfizer, Regeneron, Seagen, and Sanofi outside of the submitted work. PGR reports institutional grant support from Bristol Myers Squibb/Celgene, Karyopharm, Oncopeptides AB, and Takeda; consulting fees from Bristol Myers Squibb/Celgene, Karyopharm, and Oncopeptides AB; and honoraria from GlaxoSmithKline, Janssen, Sanofi, and Takeda outside of the submitted work. PS reports grants or contracts from Amgen, Celgene, Janssen, SkylineDx, and Takeda, and payment or honoraria from Amgen, Celgene, Janssen, SkylineDx, and Takeda outside of the submitted work. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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- 2022
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49. Mutation landscape of multiple myeloma measurable residual disease: identification of targets for precision medicine.
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Zátopková M, Ševčíková T, Fanfani V, Chyra Z, Říhová L, Bezděková R, Žihala D, Growková K, Filipová J, Černá L, Broskevičova L, Kryukov F, Minařík J, Smejkalová J, Maisnar V, Harvanová Ĺ, Pour L, Jungova A, Popková T, Bago JR, Anilkumar Sithara A, Hrdinka M, Jelínek T, Šimíček M, Stracquadanio G, and Hájek R
- Subjects
- Humans, Mutation, Neoplasm, Residual, Precision Medicine, Multiple Myeloma genetics
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- 2022
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50. Limited efficacy of daratumumab in multiple myeloma with extramedullary disease.
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Jelinek T, Sevcikova T, Zihala D, Popkova T, Kapustova V, Broskevicova L, Capkova L, Rihova L, Bezdekova R, Sevcikova S, Zidlik V, Havel M, Plonkova H, Jungova A, Minarik J, Stork M, Pour L, Pavlicek P, Spicka I, Maisnar V, Radocha J, Simicek M, and Hajek R
- Subjects
- Clone Cells pathology, Follow-Up Studies, Humans, Multiple Myeloma pathology, Plasma Cells pathology, Prognosis, Retrospective Studies, Survival Rate, Antibodies, Monoclonal therapeutic use, Antineoplastic Agents therapeutic use, Clone Cells drug effects, Multiple Myeloma drug therapy, Plasma Cells drug effects
- Published
- 2022
- Full Text
- View/download PDF
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