Experience of Daratumumab in Relapsed/Refractory Multiple Myeloma: A Multicenter Study from Türkiye

Objective: This study aimed to evaluate patients with relapsed/refractory multiple myeloma (RRMM) who underwent daratumumab (DARA) therapy. Materials and Methods: This multicenter retrospective study included 134 patients who underwent at least two courses of DARA from February 1, 2018, to April 15, 2022. Epidemiological, disease, and treatment characteristics of patients and treatment-related side effects were evaluated. Survival analysis was performed. Results: The median age at the start of DARA was 60 (range: 35-88), with 56 patients (41.8%) being female and 48 (58.2%) being male. The median time to initiation of DARA and the median follow-up time were 41.2 (5.1-223) and 5.7 (2.1-24.1) months, respectively. The overall response rate after DARA therapy was 75 (55.9%), and very good partial response or better was observed in 48 (35.8%) patients. Overall survival (OS) and progression-free survival (PFS) for all patients were 11.6 (7.8-15.5) and 8.0 (5.1-10.9) months, respectively. OS was higher for patients undergoing treatment with DARA and bortezomib-dexamethasone (DARA-Vd) compared to those undergoing treatment with DARA and lenalidomide-dexamethasone (DARA-Rd) (16.9 vs. 8.3 months; p=0.014). Among patients undergoing DARA-Rd, PFS was higher in those without extramedullary disease compared to those with extramedullary disease (not achieved vs. 3.7 months; odds ratio: 3.4; p<0.001). The median number of prior therapies was 3 (1-8). Initiation of DARA therapy in the early period provided an advantage for OS and PFS, although it was statistically insignificant. Infusion-related reactions were observed in 18 (13.4%) patients. All reactions occurred during the first infusion and most reactions were of grade 1 or 2 (94.5%). The frequency of neutropenia and thrombocytopenia was higher in the DARA-Rd group (61.9% vs. 24.7%, p<0.001 and 42.9% vs. 15.7%, p<0.001). Conclusion: Our study provides real-life data in terms of DARA therapy for patients with RRMM and supports the early initiation of DARA therapy.

Utility of Different Scoring Systems for the Diagnosis of Thrombotic Microangiopathies.

OBJECTIVE:  To investigate the appropriateness of Bentley and plasmic scores and ADAMTS-13 activity to distinguish between primary thrombotic microangiopathies (TMA) syndromes and other thrombotic microangiopathies, as well as primary thrombotic microangiopathies (TTP, complement-related TMA, etc). STUDY DESIGN:  Descriptive study. Place and Duration of the Study: Department of Hematology, Faculty of Medicine, from February 2013 to February 2020. METHODOLOGY: Data of patients with non-immune hemolytic anaemia (MAHA) and thrombocytopenia who had ADAMTS-13 test, were analysed. Clinical and laboratory findings, Bentley and plasmic scores, and ADAMTS activity levels were compared. RESULTS: The patients were grouped as primary (n = 27) and secondary (n = 28) TMA, the age was median 38.0 (18-63) years in the primary TMA group and 49.5 (20-84) years in the secondary TMA group. Neurological findings were less in the secondary TMA group (p = 0.008). Plasmic score, lactate dehydrogenase, and total and indirect bilirubin levels were high and D-dimer levels were low in the primary TMA group. In the primary TMA group, a greater number of patients with high plasmic scores were found, whereas all patients in the secondary TMA group had low risk according to Bentley score. Calcium levels were high and platelet levels were low in those with ADAMTS activity level <10% (p = 0.006). The evaluation of primary TMAs demonstrated significant differences in platelet, urea, creatinine, and sodium values between the two groups. CONCLUSION: Laboratory data and clinical scores are valuable in differentiating primary and other TMA. KEY WORDS: Bentley score, Complement, Plasmic score, Thrombotic microangiopathy, Thrombotic thrombocytopenic purpura, ADAMTS-13.

International Forum: The Turkish perspective on apheresis activity: The Turkish apheresis registry report.

Therapeutic apheresis is an extracorporeal treatment that selectively removes abnormal cells or harmful substances in the blood that are associated with or cause certain diseases. During the last decades the application of therapeutic apheresis has expanded to a broad spectrum of hematological and non-hematological diseases due to various studies on the clinical efficacy of this procedure. In this context there are more than 30 centers performing therapeutic apheresis and registered in the apheresis database in Turkey. Herein, we, The Turkish Apheresis Registry, aimed to analyze some key articles published so far from Turkey regarding the use of apheresis for various indications.

Rituximab-induced severe acute thrombocytopenia in a patient with splenic marginal zone lymphoma.

INTRODUCTION: Rituximab, which is widely used in the treatment of B-cell lymphoma, is a chimeric monoclonal antibody directed against the CD20 antigen. Rituximab has many side effects, mainly allergic and neurological. Rituximab may cause thrombocytopenia in the long term after administration. Rare cases of rituximab-induced acute thrombocytopenia have been reported in the literature. CASE REPORT: A 51-year-old female patient who was newly diagnosed with splenic marginal zone lymphoma received rituximab as first-line therapy. Petechiae occurred in the lower extremities on the day following rituximab administration. The blood test showed a severe drop in the platelet count from 112,000/µL to 5000/µL. Blood peripheral smear evaluation confirmed severe thrombocytopenia. MANAGEMENT AND OUTCOME: There was no change in hemoglobin or white blood cell levels. After the diagnosis of rituximab-induced acute thrombocytopenia, thrombocyte suspension was administered due to the risk of bleeding. Close clinical and laboratory observations were made. The platelet count began to rise gradually in the following period. Before the second week of rituximab administration, the platelet count was 122,000/µL. No complications developed after premedication and slow rituximab administration, and subsequent treatments were continued in the same way. DISCUSSION: Rituximab has widespread use, especially in malignancies and autoimmune diseases. Like many monoclonal antibodies, rituximab has several side effects. Thrombocytopenia is a long-term side effect associated with rituximab, and rituximab-induced severe acute thrombocytopenia has been rarely reported. Therefore, it should be kept in mind that severe acute thrombocytopenia may develop after rituximab administration.

Effects of idiopathic erythrocytosis on the left ventricular diastolic functions and the spectrum of genetic mutations: A case control study.

BACKGROUND: We have aimed at exposing left ventricular diastolic functions and the presence of known genetic mutations for familial erythrocytosis, in patients who exhibit idiopathic erythrocytosis. METHODS: Sixty-four patients with idiopathic erythrocytosis (mean age, 46.4 ± 2.7 years) and 30 age-matched healthy subjects were prospectively evaluated. The regions of interest of the erythropoietin receptor, hemoglobin beta-globin, von Hippel-Lindau, hypoxia-inducible factor 2 alpha, and Egl-9 family hypoxia-inducible factor genes were amplified by PCR. Left ventricular (LV) mass was measured by M-mode and 2-dimensional echocardiography. LV diastolic functions were assessed by conventional echocardiography and tissue Doppler imaging. RESULTS: As a result of genetic analyses, genetic mutations for familial erythrocytosis were detected in 5 patients. It has been observed in our study that the risk of cardiovascular disorders is higher in patients. Interventricular septum thickness, left atrial diameter, and some diastolic function parameters such as deceleration time and isovolumetric relaxation time have been found to be significantly higher in idiopathic erythrocytosis group than in the controls. CONCLUSION: This study has shown that LV diastolic functions were impaired in patients with idiopathic erythrocytosis. In this patient group with increased risk of cardiovascular disorders, the frequent genetic mutations have been detected in 5 patients only. Therefore, further clinical investigations are needed as novel genetic mutations may be discovered in patients with idiopathic erythrocytosis because of cardiovascular risk.

Anaplastic Multiple Myeloma with Multiple Genetic Anomalies.

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The Real-World Experience With Single Agent Ibrutinib in Relapsed/Refractory CLL.

INTRODUCTION/BACKGROUND: The emergence of novel agents targeting the B-cell receptor pathway and BCL-2 has significantly changed the therapeutic landscape of CLL. We evaluated the safety and efficacy of single-agent ibrutinib in relapsed/refractory CLL in real-world settings. PATIENTS/METHODS: A total of 200 relapsed/refractory CLL patients with a median age of 68 were included in this retrospective, multicenter, non-interventional study. Data of the study were captured from the patient charts of the participating centers. RESULTS: The median for lines of previous chemotherapy was 2 (1-6); 62 (31.8%) patients had del17p and/or p53 mutations (del17p+/p53mut). Of the study group, 146 (75%) patients achieved at least PR, while 16 (8.7%) patients discontinued ibrutinib due to TEA. The most common drug-related adverse events were neutropenia (n: 31; 17.4%) and thrombocytopenia (n: 40; 22.3%), which were ≥ grade 3 in 9 (5%) and 5 (3.9%) patients, respectively. Pneumonia (n: 42; 23.7%) was the most common nonhematologic TEA. Atrial fibrillation (n: 5; 2.8%) and bleeding (n: 11; 6.3%) were relatively rare during the study period. Within a median follow-up period of 17 (1-74) months, 42 (21%) patients died. The estimated median OS of the study cohort was 52 months. Only the response to ibrutinib (CR/PR vs. SD/PD) was significantly associated with OS. CONCLUSION: Our results indicate good safety and efficacy for single-agent ibrutinib in R/R CLL in daily practice.

Treatment with doxorubicin-based protocol in cardiac involvement diffuse large B-cell lymphoma: A case report.

INTRODUCTION: Cardiac involvement in diffuse large B-cell lymphoma is a rare entity in non-Hodgkin lymphomas. Symptoms are usually related to heart failure. Patients who are severely symptomatic due to cardiac mass could be considered treatment as soon as possible. In this report, we present a patient diagnosed with diffuse large B-cell lymphoma with cardiac involvement. CASE REPORT: A 61-year-old female patient was admitted to our unit with gastric biopsy diffuse large B-cell lymphoma. Computerized tomography of the chest and positron emission tomography/computed tomography demonstrated a neoplastic mass in the intra-atrial septum extended to inferior vena cava (5 × 4 cm in size and standardized uptake value maximum 24.6). She was in stage III and in the high-risk group. Because of pronounced heart failure findings associated with the mass-specific chemotherapy was planned early. MANAGEMENT & OUTCOME: Although a fraction of ejection was 60% by echocardiography before the treatment, she had a cardiac risk for doxorubicin due to being over 60 years old and hypertension. Complete remission was achieved after three cycles of rituximab-cyclophosphamide-doxorubicin-vincristine and methylprednisolone protocol including doxorubicin. Treatment was completed with six cycles and she was followed up for three months. DISCUSSION: Because of the cardiotoxicity of doxorubicin-based protocols, patients should be evaluated according to cardiac functions before and during the chemotherapy.

A Real-life Turkish Experience of Venetoclax Treatment in High-risk Myelodysplastic Syndrome and Acute Myeloid Leukemia.

INTRODUCTION: Venetoclax is a selective B-cell lymphoma 2 (BCL2) inhibitor, which is approved to treat elderly patients with newly diagnosed acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) in combination with either low-dose cytarabine (ARA-C) or hypomethylating agents. We aimed to collect and share data among the efficacy and safety of venetoclax both as a monotherapy or in combination with other drugs used to treat high-risk MDS or AML. MATERIALS AND METHODS: A total of 60 patients with a median age of 67 (30-83) years from 14 different centers were included in the final analysis. Thirty (50%) of the patients were women; 6 (10%) of the 60 patients were diagnosed with high-risk MDS and the remaining were diagnosed with AML. RESULTS: The best objective response rate (complete remission [CR], complete remission with incomplete hematological recovery (CRi), morphological leukemia-free state [MLFS], partial response [PR]) was 35% in the entire cohort. Best responses achieved during venetoclax per patient number were as follows: 7 CR, 1 CRi, 8 MLFS, 5 PR, and stable disease. Median overall survival achieved with venetoclax was 5 months in patients who relapsed and not achieved in patients who were initially treated with venetoclax. Nearly all patients (86.7%) had experienced a grade 2 or more hematologic toxicity. Some 36.7% of these patients had received granulocyte colony stimulating factor (GCSF) support. Infection, mainly pneumonia (26.7%), was the leading nonhematologic toxicity, and fatigue, diarrhea, and skin reactions were the others reported. CONCLUSION: Our real-life data support the use of venetoclax in patients with both newly diagnosed and relapsed high-risk MDS and AML.

Efficacy of convalescent plasma therapy in severe COVID-19 patients.

INTRODUCTION: The use of convalescent plasma (CP) transfusions is very valuable in the current COVID-19 outbreak, given that there are no specific preventive and therapeutic options. MATERIALS AND METHODS: 50 patients with severe COVID-19 disease treated with convalescent plasma transfusion were included in the study. The efficacy of CP and in which situations it was effective were investigated. CONCLUSION: 80 % of the patients recovered, and 20 % died in our study. The mean age of the patients who died was found to be higher than the patients who recovered. CRP, ferritin, D-dimer, neutrophil, MPV, and NLR counts were found to be higher, and lymphocyte and platelet counts were lower in the deceased group after CP. It was determined that patients who received CP within the first five days were hospitalized for a shorter period. DISCUSSION: Administration of CP transfusion within the first five days in severe COVID-19 patients has been shown to reduce hospital stay length.

Bing-Neel syndrome: A case reports.

INTRODUCTION: Bing-Neel syndrome (BNS) is a rare complication of of Waldenström macroglobulinemia (WM) identified by involvement of central nervous system (CNS) lymphoplasmacytic cells. CASE REPORT: We present a patient who was diagnosed with Bing-Neel syndrome four years after the diagnosis of Waldenström macroglobulinemia. MANAGEMENT & OUTCOME: The patient was admitted with neurological symptoms. There were lesions associated with WM involvement on brain imaging. The diagnosis was made by brain biopsy. High dose methotrexate treatment was given. DISCUSSION: CNS infiltrating agents such as fludarabine, methotrexate and cytarabine are often used in BNS treatment. Ibrutinib, which is a new bruton tyrosine kinase inhibitor, has recently started to be used in BNS treatment, as it has been shown to be effective and penetrate the CNS.

A Multi-Center Study on the Efficacy of Eltrombopag in Management of Refractory Chronic Immune Thrombocytopenia: A Real-Life Experience

Objective: The aim of the present study was to evaluate the efficacy and safety of eltrombopag, an oral thrombopoietin receptor agonist, in patients with chronic immune thrombocytopenia (ITP). Materials and Methods: A total of 285 chronic ITP patients (187 women, 65.6%; 98 men, 34.4%) followed in 55 centers were enrolled in this retrospective cohort. Response to treatment was assessed according to platelet count (/mm3) and defined as complete (platelet count of >100,000/mm3), partial (30,000-100,000/mm3 or doubling of platelet count after treatment), or unresponsive (<30,000/mm3). Clinical findings, descriptive features, response to treatment, and side effects were recorded. Correlations between descriptive, clinical, and hematological parameters were analyzed. Results: The median age at diagnosis was 43.9±20.6 (range: 3-95) years and the duration of follow-up was 18.0±6.4 (range: 6-28.2) months. Overall response rate was 86.7% (n=247). Complete and partial responses were observed in 182 (63.8%) and 65 (22.8%) patients, respectively. Thirty-eight patients (13.4%) did not respond to eltrombopag treatment. For patients above 60 years old (n=68), overall response rate was 89.7% (n=61), and for those above 80 years old (n=12), overall response rate was 83% (n=10). Considering thrombocyte count before treatment, eltrombopag significantly increased platelet count at the 1st, 2nd, 3rd, 4th, and 8th weeks of treatment. As the time required for partial or complete response increased, response to treatment was significantly reduced. The time to reach the maximum platelet levels after treatment was quite variable (1-202 weeks). Notably, the higher the maximum platelet count after eltrombopag treatment, the more likely that side effects would occur. The most common side effects were headache (21.6%), weakness (13.7%), hepatotoxicity (11.8%), and thrombosis (5.9%). Conclusion: Results of the current study imply that eltrombopag is an effective therapeutic option even in elderly patients with chronic ITP. However, patients must be closely monitored for response and side effects during treatment. Since both response and side effects may be variable throughout the follow-up period, patients should be evaluated dynamically, especially in terms of thrombotic risk factors.