7 research outputs found
Addition of elotuzumab to lenalidomide and dexamethasone for patients with newly diagnosed, transplantation ineligible multiple myeloma (ELOQUENT-1): an open-label, multicentre, randomised, phase 3 trial
On improving environmental protection of associated formation water return in the interior of the Eart
The decrease in the concentration of iron ions (II) in the preparation of iodine from the fossil groundwater of oil/gas-condensate fields of Ukraine by ozonation has been studied, the degree of conversion of iron (II) to iron (III) has been estimated and it has been established that at ozonizing a mixture of Fe2+ ions with J- ions on the dependence of the degree of Fe2+/J- iodine formation the maximum is observed upon reaching of which J- ions mainly enter into a reaction, which indicates the possibility of extraction of iodine from the fossil groundwater, the ozonation accelerates the process of conversion of iron ions (II) into iron ions (III), which after coagulation are precipitating with suspended substances, which improves the process of preparing the associated fossil groundwater before the return and has an impact on the environmental safetyИсследовано уменьшение концентрации ионов железа (ІІ) при получении йода из попутно-пластовых вод нефтегазоконденсатных месторождений Украины озонированием, оценено степень превращения железа (ІІ) в железо (ІІІ), установлено, что при озонировании смеси ионов Fe2+ с ионами J- на зависимость степени образования йода Fe2+/J- наблюдается максимум, по достижению которого преимущественно в реакцию вступают ионы J-, что указывает на возможность извлечения йода из ППВ, озонирование ускоряет процесс превращения ионов железа (ІІ) в ионы железа (ІІІ), которые коагулируя выпадают в осадок вместе со взвешенными веществами, что улучшает процесс подготовки попутно-пластовых вод до возврата и влияет на экологическую безопасностьДосліджено зменшення концентрації іонів заліза (ІІ) при одержанні йоду з супутньо-пластових вод нафтогазоконденсатних родовищ України озонуванням, оцінено ступінь перетворення заліза (ІІ) в залізо (ІІІ), встановлено, що при озонуванні суміші іонів Fe2+ з іонами J- на залежності ступеня утворення йоду від співвідношенні Fe2+/J- спостерігається максимум, до досягнення якого переважно в реакцію вступають іони йоду, що вказує на можливість вилучення йоду з СПВ, озонування прискорює процес перетворення іонів заліза (ІІ) в іони заліза (ІІІ), які коагулюючи випадають у осад разом з завислими речовинами, що покращує процес підготовки супутньо-пластових вод до повернення та впливає на екологічну безпеку
Neurolymphomatosis: An International Primary CNS Lymphoma Collaborative Group report
Neurolymphomatosis (NL) is a rare clinical entity. The International Primary CNS Lymphoma Collaborative Group retrospectively analyzed 50 patients assembled from 12 centers in 5 countries over a 16-year period. NL was related to non-Hodgkin lymphoma in 90% and to acute leukemia in 10%. It occurred as the initial manifestation of malignancy in 26% of cases. The affected neural structures included peripheral nerves (60%), spinal nerve roots (48%), cranial nerves (46%), and plexus (40%) with multiple site involvement in 58%. Imaging studies often suggested the diagnosis with 77% positive magnetic resonance imaging, and 84% (16 of 19) positive computed tomography-positron emission tomography studies. Cerebrospinal fluid cytology was positive in 40%, and nerve biopsy confirmed the diagnosis in 23 of 26 (88%). Treatment in 47 patients included systemic chemotherapy (70%), intra-cerebrospinal fluid chemotherapy (49%), and radiotherapy (34%). Response to treatment was observed in 46%. The median overall survival was 10 months, with 12- and 36-month survival proportions of 46% and 24%, respectively. NL is a challenging diagnosis, but contemporary imaging techniques frequently detect the relevant neural invasion. An aggressive multimodality therapy can prevent neurologic deterioration and is associated with a prolonged survival in a subset of patients
MDS-Related Anemia Is Associated with Impaired Quality of Life but Improvement Is Not Always Achieved by Increased Hemoglobin Level
Quality of life is impaired in MDS, but the role of hemoglobin level is unclear. To study the Hb–QoL correlation at diagnosis and 1 year later, patients filled out the EQ-5D questionnaire, assessing their mobility, self care, daily activities, pain/discomfort, and anxiety/depression, using scores of 0 (normal), 1 (mild/moderate), or 2 (poor). They also evaluated their health using a visual analogue scale, scoring from 0 (poor) to 100 (excellent). The anemia subgroups were: none/normal (Hb ≥ 12.5 g/dL), mild (10 ≤ Hb < 12.5), moderate (9 ≤ Hb < 10), severe (8 ≤ Hb < 9), or very severe (Hb < 8). LR-MDS patients (n = 127) and inpatient controls (n = 141) participated. The anemic patients had a poor QoL and the MDS patients had a lower QoL with a lower Hb. The controls had no QoL difference among the various anemia subgroups. In addition, the MDS QoL sharply decreased with an Hb of < 9. The MDS patients showed a wide QoL variability, i.e., different QoL scores in the same Hb subgroup, suggesting that other factors affect QoL (e.g., age and comorbidities). After 1 year (n = 61), the QoL was still poor for most MDS patients (including 27 patients with an increased Hb). In summary: (1) a poor QoL in MDS-anemia is non-linear, suggesting other influencing factors on QoL. (2) The sharp QoL drop with Hb < 9 g/dL challenges the transfusion Hb threshold. (3) The QoL in anemic MDS patients might differ from that in non-MDS patients. (4) Raising Hb, while recommended, does not guarantee an improved QoL
Frontline treatment with the combination obinutuzumab ± chlorambucil for chronic lymphocytic leukemia outside clinical trials: Results of a multinational, multicenter study by ERIC and the Israeli CLL study group
In recent years, considerable progress has been made in frontline therapy for elderly/physically unfit patients with CLL. The combination of obinutuzumab and chlorambucil (O-Clb) has been shown to prolong progression free survival (PFS, median PFS-31.5 months) and overall survival (OS) compared to chlorambucil alone. More recently, obinutuzumab given in combination with either ibrutinib or venetoclax improved PFS but not OS when compared to O-Clb. In this retrospective multinational, multicenter co-operative study, we evaluated the efficacy and safety of frontline treatment with O ± Clb in unfit patients with CLL, in a “real-world” setting. Patients with documented del (17p13.1)/TP53 mutation were excluded. A total of 437 patients (median age, 75.9 years; median CIRS score, 8; median creatinine clearance, 61.1 mL/min) were included. The clinical overall response rate was 80.3% (clinical complete and partial responses in 38.7% and 41.6% of patients, respectively). Median observation time was 14.1 months and estimated median PFS was 27.6 months (95% CI, 24.2-31.0). In a multivariate analysis, high-risk disease [del (11q22.3) and/or IGHV-unmutated], lymph nodes of diameter > 5 cm, obinutuzumab monotherapy and reduced cumulative dose of obinutuzumab, were all independently associated with shorter PFS. The median OS has not yet been reached and estimated 2-year OS is 88%. In conclusion, in a “real-world” setting, frontline treatment with O-Clb achieves PFS comparable to that reported in clinical trials. Inferior outcomes were noted in patients with del (11q22.3) and/or unmutated IGHV and those treated with obinutuzumab-monotherapy. Thus, O-Clb can be still considered as legitimate frontline therapy for unfit CLL patients with low-risk disease.Fil: Herishanu, Yair. Universitat Tel Aviv; IsraelFil: Shaulov, Adir. Hadassah Hebrew University Medical Center; IsraelFil: Fineman, Riva. Rambam Health Care Campus; IsraelFil: Basik Kinda, Sandra. University Hospital Centre Zagreb; CroaciaFil: Aviv, Ariel. Technion - Israel Institute of Technology; IsraelFil: Wasik Szczepanek, Ewa. Medical University of Lublin; PoloniaFil: Jaksic, Ozren. Dubrava University Hospital, Zagreb; CroaciaFil: Zdrenghea, Mihnea. Luliu Hatieganu University Of Medicine And Pharmacy; RumaniaFil: Greenbaum, Uri. oroka University Medical Center; Israel. Ben Gurion University; IsraelFil: Mandac, Inga. Clinical Hospital Merkur; CroaciaFil: Simkovic, Martin. University Hospital And Medical School Hradec Kralove; República ChecaFil: Morawska, Marta. St. John's Cancer Center; PoloniaFil: Benjamini, Ohad. Chaim Sheba Medical Center, Ramat Gan; IsraelFil: Spacek, Martin. Charles University And General Hospital In Prague; República ChecaFil: Nemets, Anatoly. Barzilai University Medical Center; IsraelFil: Bairey, Osnat. Universitat Tel Aviv; IsraelFil: Trentin, Livio. Università di Padova; ItaliaFil: Ruchlemer, Rosa. Shaare Zedek Medical Center; IsraelFil: Laurenti, Luca. Fondazione Policlinico Universitario Agostino Gemelli; ItaliaFil: Ciocan, Oana Stanca. Coltea Clinical Hospital; RumaniaFil: Doubek, Michael. University Hospital Brno; República Checa. Masaryk University; República ChecaFil: Shvidel, Lev. The Hebrew University of Jerusalem; IsraelFil: Dali, Nagib. Ziv Medical Center; IsraelFil: Mirás, Fátima. Hospital 12 de Octubre; EspañaFil: De Meûter, Anne. Institut Jules Bordet; BélgicaFil: Dimou, María. Laikon Hospital; GreciaFil: Mauro, Francesca R.. Università degli Studi di Roma "La Sapienza"; ItaliaFil: Coscia, Marta. Università di Torino; ItaliaFil: Bumbea, Horia. Emergency University Clinical Hospital; RumaniaFil: Slavutsky, Irma Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin
Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial
Background Maintenance therapy following autologous stem cell transplantation (ASCT) can delay disease progression and prolong survival in patients with multiple myeloma. Ixazomib is ideally suited for maintenance therapy given its convenient once-weekly oral dosing and low toxicity profile. In this study, we aimed to determine the safety and efficacy of ixazomib as maintenance therapy following ASCT. Methods The phase 3, double-blind, placebo-controlled TOURMALINE-MM3 study took place in 167 clinical or hospital sites in 30 countries in Europe, the Middle East, Africa, Asia, and North and South America. Eligible participants were adults with a confirmed diagnosis of symptomatic multiple myeloma according to International Myeloma Working Group criteria who had achieved at least a partial response after undergoing standard-of-care induction therapy followed by high-dose melphalan (200 mg/m2) conditioning and single ASCT within 12 months of diagnosis. Patients were randomly assigned in a 3:2 ratio to oral ixazomib or matching placebo on days 1, 8, and 15 in 28-day cycles for 2 years following induction, high-dose therapy, and transplantation. The initial 3 mg dose was increased to 4 mg from cycle 5 if tolerated during cycles 1–4. Randomisation was stratified by induction regimen, pre-induction disease stage, and response post-transplantation. The primary endpoint was progression-free survival (PFS) by intention-to-treat analysis. Safety was assessed in all patients who received at least one dose of ixazomib or placebo, according to treatment actually received. This trial is registered with ClinicalTrials.gov, number NCT02181413, and follow-up is ongoing. Findings Between July 31, 2014, and March 14, 2016, 656 patients were enrolled and randomly assigned to receive ixazomib maintenance therapy (n=395) or placebo (n=261). With a median follow-up of 31 months (IQR 27·3–35·7), we observed a 28% reduction in the risk of progression or death with ixazomib versus placebo (median PFS 26·5 months [95% CI 23·7–33·8] vs 21·3 months [18·0–24·7]; hazard ratio 0·72, 95% CI 0·58–0·89; p=0·0023). No increase in second malignancies was noted with ixazomib therapy (12 [3%] patients) compared with placebo (eight [3%] patients) at the time of this analysis. 108 (27%) of 394 patients in the ixazomib group and 51 (20%) of 259 patients in the placebo group experienced serious adverse events. During the treatment period, one patient died in the ixazomib group and none died in the placebo group. Interpretation Ixazomib maintenance prolongs PFS and represents an additional option for post-transplant maintenance therapy in patients with newly diagnosed multiple myeloma. Funding Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical Company
Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial
Background
Maintenance therapy following autologous stem cell transplantation (ASCT) can delay disease progression and prolong survival in patients with multiple myeloma. Ixazomib is ideally suited for maintenance therapy given its convenient once-weekly oral dosing and low toxicity profile. In this study, we aimed to determine the safety and efficacy of ixazomib as maintenance therapy following ASCT.
Methods
The phase 3, double-blind, placebo-controlled TOURMALINE-MM3 study took place in 167 clinical or hospital sites in 30 countries in Europe, the Middle East, Africa, Asia, and North and South America. Eligible participants were adults with a confirmed diagnosis of symptomatic multiple myeloma according to International Myeloma Working Group criteria who had achieved at least a partial response after undergoing standard-of-care induction therapy followed by high-dose melphalan (200 mg/m2) conditioning and single ASCT within 12 months of diagnosis. Patients were randomly assigned in a 3:2 ratio to oral ixazomib or matching placebo on days 1, 8, and 15 in 28-day cycles for 2 years following induction, high-dose therapy, and transplantation. The initial 3 mg dose was increased to 4 mg from cycle 5 if tolerated during cycles 1–4. Randomisation was stratified by induction regimen, pre-induction disease stage, and response post-transplantation. The primary endpoint was progression-free survival (PFS) by intention-to-treat analysis. Safety was assessed in all patients who received at least one dose of ixazomib or placebo, according to treatment actually received. This trial is registered with ClinicalTrials.gov, number NCT02181413, and follow-up is ongoing.
Findings
Between July 31, 2014, and March 14, 2016, 656 patients were enrolled and randomly assigned to receive ixazomib maintenance therapy (n=395) or placebo (n=261). With a median follow-up of 31 months (IQR 27·3–35·7), we observed a 28% reduction in the risk of progression or death with ixazomib versus placebo (median PFS 26·5 months [95% CI 23·7–33·8] vs 21·3 months [18·0–24·7]; hazard ratio 0·72, 95% CI 0·58–0·89; p=0·0023). No increase in second malignancies was noted with ixazomib therapy (12 [3%] patients) compared with placebo (eight [3%] patients) at the time of this analysis. 108 (27%) of 394 patients in the ixazomib group and 51 (20%) of 259 patients in the placebo group experienced serious adverse events. During the treatment period, one patient died in the ixazomib group and none died in the placebo group.
Interpretation
Ixazomib maintenance prolongs PFS and represents an additional option for post-transplant maintenance therapy in patients with newly diagnosed multiple myeloma.
Funding
Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical Company