Daratumumab is a human anti-CD38 monoclonal antibody used in the treatment of refractory and relapsed multiple myeloma. We investigated the efficacy and safety of daratumumab therapy in a real-world setting. Ninety-nine Hungarian patients were included; 48 received monotherapy, while lenalidomide and bortezomib combinations were administered in 29 and 19 cases, respectively. Overall response rate was assessable in 88 patients, with 12 complete, 10 very good partial, 34 partial, and seven minor responses. At a median duration of follow-up of 18.6 months, median progression-free survival (PFS) among all patients was 17.0 months. These values were inferior in the bortezomib combination and monotherapy groups. Patients with early-stage disease (ISS1) had better survival results than those with stage 2 or 3 myeloma (p = 0.009). Heavily pretreated patients had inferior PFS compared to those with 1-3 therapies (p = 0.035). Patients with impaired renal function had PFS results comparable with those having no kidney involvement. There were 10 fatal infections, and the most frequent adverse events were mild infusion-associated reactions and hematologic toxicities. Our results confirm that daratumumab is an effective treatment option for relapsed/refractory MM with an acceptable safety profile in patients with normal and impaired renal function.

Because of the widespread use of immunosuppressive drugs, CMV infection is one of the most important causes of morbidity and mortality in patients with haematological malignancies worldwide. The aim of the study was to retrospectively analyse the epidemiology of CMV infection in haematological patients. Between 2008 and 2014, 1238 quantitative CMV DNA detections from plasma specimens were performed. These specimens were collected from 271 patients with haematological malignancy. Patients were grouped on the basis of underlying diseases (lymphoid and myeloid malignancies and other haematological diseases). In the lymphoid and myeloid groups, we distinguished ASCT and non-ASCT groups. During the studied period, the majority of examined patients (82.6 %) were treated with lymphoproliferative disease. A total of 126 (46.5 %) patients underwent ASCT, while 145 (53.5 %) did not have stem cell transplantation. A total of 118 (9.5 %) of 1238 plasma specimens proved to be positive for CMV DNA; these specimens were collected from 66 (24.4 %) patients. Twenty-four (16.6 %) of 145 non-ASCT patients had CMV PCR positive specimens. Among non-ASCT patients with positive CMV PCR results, 10 patients were asymptomatic, 14 had symptomatic reactivation, while 2 had CMV disease. In the ASCT group, 42 (33.3 %) patients had CMV PCR positive samples. CMV reactivation was asymptomatic in 34 (81 %) cases, and 8 (19 %) patients had symptomatic reactivation. In the non-ASCT group, the rate of CMV infection is low. In the ASCT group, the prevalence of CMV infection was higher than in the non-ASCT group, but the majority of CMV infection was asymptomatic and only small number of patients had symptomatic reactivation. Thus, our results also showed that the use of routine CMV DNA monitoring is not necessary in patients with haematological malignancies not receiving fludarabine-containing regimen or alemtuzumab, in spite of this to decrease the mortality we have to consider the use of molecular tests in case of suspected infectious conditions.

Background and Objectives:Therapy-resistant immune thrombocytopenia (ITP) is the most frequent indication of laparoscopic splenectomy (LS). It ensures the best results for this disease compared with possible second-line pharmacologic therapies. Therefore, learning about the safety of the surgical method and its long-term efficacy is important, as is selecting patients who respond to surgical treatment. Our purpose was to analyze the safety of LS and the short-and long-term prognostic significance of known perioperative parameters.Methods:We performed 40 LSs for ITP from January 1, 2000, to January 1, 2015. We analyzed the roles of the perioperative parameters by using evidence-based guidelines.Results:Complete response (CR; platelet count over 100 × 109/L) occurred in 28 cases (70%) and partial response (PR; platelet count between 30 and 100 × 109/L) in 5 cases (12.5%). Below the age of 50, 9% (2/22) of the patients had no response (NR; platelet count not increasing over 30 × 109/L), 28% (5/18) over the age of 50 (P = .023) had no response. In the steroid-refractory group, 30% did not respond, whereas 100% of the steroid-dependent patients had a CR (NR: 7/23 steroid refractory vs 0/17 steroid dependent; P = .027). The patients were followed up for a mean of 10.9 ± 6.9 years, and a long-term response (LTR) was detected in 21 of the responders (n = 33). Of the patients who originally had a CR, 71% also achieved LTR, whereas only 20% of the PR patients did.Conclusion:LS is safe and remains the most effective second-line treatment for ITP. In our study, younger age and response to preoperative steroids were predictive factors for the long-term success of splenectomy.

Background: Daratumumab is one of the most effective new myeloma drugs recently approved for relapsed/refractory multiple myeloma (MM), first in monotherapy in heavily pretreated patients, later in triplet combinations from first relapse, based on the results of the SIRIUS, POLLUX and CASTOR trials that showed good tolerability and high effectivity of daratumumab both in monotherapy and combined with lenalidomide or bortezomib. However, clinical trials are different from real world use for many reasons including less rigorous patient selection, greater flexibility with dosing and country specific funding restrictions making real world data very important for clinicians. Real world data regarding daratumumab use is currently very limited. In the Hungarian system, funding of daratumumab was initiated in December 2016, and required individual preapproved funding requests. Initially only monotherapy was reimbursed in double-refractory patients, but from 2018 triplet combination in earlier lines could start as well. Aims and Methods: The aim of this study was to evaluate the efficacy and safety of daratumumab in the real world practice. We approached all centers in Hungary where daratumumab was used, in a retrospective analysis. The scope of this study was to analyze response rate, progression free survival (PFS), treatment duration, and adverse events (AEs). Statistical analyses were performed using the SPSS (version 20.0) software package. Results: 8 centers responded with 75 patients altogether. Patients were heavily pretreated, the median number of prior lines was 3 (1-12). All patients had prior bortezomib, and most had lenalidomide (82.6%) and thalidomide (86.6%), all but one had one of the two IMiDs. 62.6% of the patients had prior autologous transplantation, with two having prior allograft, as well. Pre-daratumumab cytogenetic FISH tests of 57 patients were available, here 33/57 had high risk cytogenetics. The majority had high international staging system (ISS) score: 8, 16 and 48 were in the ISS 1, 2 and 3 groups respectively. Treatment usually continued until progression, unacceptable toxicity or death, the mean number of cycles was 6. AEs over grade 3 were uncommon, the most frequent AEs were mild infusion associated reactions (IARs, grade 1-2) and infections (Table 1). There were 7 fatal infections, other fatal AEs were absent. Infusion related toxicities were manageable in all cases. The majority of patients (41) had monotherapy with dexamethasone only, but 17 had bortezomib and another 17 lenalidomide combination. Overall response rate was assessable in 66 patients with 7 complete, 8 very good partial, 24 partial, 5 minor responses. 14 showed stable disease, 8 progressive disease. 9 patients had no formal disease reassessment due to either early death or short follow up. There was no clear connection between the number of prior lines and the quality of the response, however those who had either bortezomib or lenalidomid combinations showed better overall response rate (p=0.045). With 43 events so far the estimated PFS and OS were 151 and 260 days, but it was much better in those who showed at least a partial response (PFS 400 days, OS nor reached; Figure 1). The only other factor that significantly affected the PFS was ISS (p=0.039), we could not demonstrate a significant connection between cytogenetics, the number of prior lines, combination therapy and survival. Conclusion: Our results highlight the differences between patients treated in routine practice and those treated in clinical trials. Here treatment protocols were dictated by funding rules, and therefore similar patients were treated with doublets and triplets. The results of the POLLUX and CASTOR trials were superior in comparison to the SIRIUS study with monotherapy, but our results do not reflect this marked difference, probably due to the almost complete absence of 2nd and 3rd line patients who dominated the Pollux and Castor trials. Importantly these heavily pretreated patients tolerated daratumumab well, IARs over grade 2 were absent. Based on our results, daratumumab is an effective treatment option for relapsed/refractory MM with good safety profile. Disclosures Masszi: Janssen-Cilag: Consultancy; Takeda: Consultancy; AbbVie: Consultancy; Pfizer: Consultancy; Novartis: Consultancy; BMS: Consultancy. Illés:Takeda: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees.

A laparoszkópos splenectomia 1991-es bevezetése óta gold standard módszer a lép sebészetében, és előnyei vitathatatlanná váltak a nyitott műtéttel szemben. A technika 1994-ben került bevezetésre a Szegedi Tudományegyetem Sebészeti Klinikáján, és az azóta eltelt időben munkacsoportunk szerezte az egyik legnagyobb tapasztalatot ezen a területen Magyarországon. Eredményeink az irodalmi adatokkal korrelálva alátámasztják, hogy a laparoszkópos lépeltávolítás biztonságos, és számos előnnyel jár a szükséges sebészi tapasztalat megszerzését követően. Vizsgálatunk során a bélpasszázs hamarabb indult be, és a hospitalizáció is rövidebb volt laparoszkópos műtétet követően. Igazoltuk, hogy a laparoszkópos splenectomia biztonságos módszer extrém nagy lépek esetében is, a lép eltávolítására a Pfannenstiel-metszés kozmetikailag is kiváló alternatíva. Habár számos új gyógyszer áll rendelkezésre az ITP második vonalbeli terápiájára, a laparoszkópos lépeltávolítás biztosítja a legtartósabb eredményeket. Saját retrospektív vizsgálatunkban mind a fiatal életkor, mind a preoperatív szteroidra adott válasz (szteroid dependens esetek), mind a perioperatív thrombocytaszám pozitív prediktív faktora volt a splenectomia hosszú távú sikerességének. Megfigyelésünk szerint a splenectomiára adott azonnali komplett válasz esetén a relapszus szignifikánsan ritkábban jelent meg.