Kooperativer Bibliotheksverbund

In: HemaSphere, Ovid Technologies (Wolters Kluwer Health), Vol. 7, No. S3 ( 2023-08), p. e23759a8-

Materialart: Online-Ressource

ISSN: 2572-9241

URL: Article

DOI: 10.1097/01.HS9.0000973640.23759.a8

Sprache: Englisch

Verlag: Ovid Technologies (Wolters Kluwer Health)

Publikationsdatum: 2023

ZDB Id: 2922183-3

In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 28-29

Kurzfassung: The goal of treatment of relapsed/refractory multiple myeloma (RRMM) is to control the disease, prolong survival, reduce disease-related symptoms, and improve quality of life (QoL). Comprehensive evaluation of new treatment regimens in RRMM pts is worthwhile. We aimed to evaluate QoL, treatment satisfaction, response to treatment and safety during Ixazomib-Lenalidomide-Dexamethasone (IRd) treatment as ≥ 2nd line in RRMM pts in a real world setting. Adult pts with RRMM who have been assigned IRd as ≥2nd line treatment were enrolled in multicenter observational prospective study. Treatment response was evaluated by IMWG 2011, adverse events (AEs) - by CTCAE v.4.0. Pts filled out RAND SF-36 and ESAS-R at baseline and at 1 and 3 mos, and thereafter every 3 mos till 18 mos after IRd treatment start; Patient Treatment Satisfaction Cheklist (PTSC) - at each time-point after IRd treatment start. For analysis of meaningful QoL changes during IRd treatment the proportion of pts with baseline significant QoL impairment who experienced meaningful QoL improvement during IRd treatment was evaluated as well as the number of pts without baseline QoL impairment who maintained it during IRd treatment. For statistical analysis GLM paired test and GEE were employed with adjustment to age, gender and baseline QoL. In total, 40 pts with RRMM were enrolled into the pilot study: median age - 64 years (range, 33-80), 29% males, Durie-Salmon stage at study entry: I/II/III - 3/41/56%, ECOG status 0/1 - 68.7%, 2/3 - 31.6%. Median time since initial MM diagnosis - 51.4 mos (range, 2.9-100.7), disease status at study entry: relapsed - 26%, refractory - 21%, relapsed and refractory - 53%. Median number of lines of prior therapy is 3 (range, 1-3). At the time of analysis the median number of IRd cycles administered is 5, median follow-up - 4.6 (0.4-13.7) mos. Treatment response was not evaluated in 11 pts: 1 - death (at 3 months), 1- refusal, 9 - too early for evaluation. Out from 29 pts one patient achieved complete response (CR), seven pts achieved partial response (PR) and one patient - very good partial response (VGPR), 12 - minor response (MR). Thus, a clinical benefit rate was 70%. Also, seven pts achieved stable disease (23%), one patient was primary refractory to IRd (3.5%), one patient died (3.5%). At the time of analysis all the pts with CR/PR/VGPR (30%) maintained their response to treatment, 4 pts (13%) maintained stable disease and 9 pts (30%) maintained minor response; 7 pts (23%) experienced disease progression. AEs were revealed in 47% pts: grades 1-2 AEs - 12 pts; grades 3-4 AEs - 4 pts; SAEs - 3 pts (neurological toxicity, gastric bleeding, hypotension), all pts with SAEs discontinued IRd treatment. Baseline QoL was dramatically impaired by the majority of SF-36 scales with significant QoL impairment in 42% pts. The most worsening was revealed for physical functioning, role functioning, general health and vitality (Mean scores varied from 24.6 to 47.0 out from 100 scores). At baseline 88% pts had moderate-to severe symptoms (≥4 scores on the scale from 0 to 10); moderate-to severe worse wellbeing, tiredness, pain and shortness of breath had 72,5%, 67,5%, 61,5% and 45% pts, respectively. At 1 month of IRd treatment QoL meaningfully improved or was stable without significant impairment in 61% pts, at 3 months - in 50% pts. In 1 mos of IRd treatment significant improvement was revealed for physical functioning (GLM, 44.9 vs 54.7, p=.01) and general health (GLM, 47.8 vs 56.3, p & lt;.001). Further during IRd treatment no significant QoL worsening was identified (GEE, p & gt;.05). At 1 month of treatment, meaningful decrease of shortness of breath (in 42% pts), tiredness (36%), and pain (28%) was revealed; at 3 months of IRd treatment this proportion was 33%, 27%, and 13%, accordingly. Regarding treatment satisfaction pts reported the following: at 1 month after treatment start 94% of pts were satisfied with symptoms decrease due to IRd, 89% pts confirmed that IRd was convenient and 97% pts reported global satisfaction with IRd; at 3 months of treatment all the pts confirmed the convenience of IRd regimen, 84% pts were satisfied with IRd treatment. The results obtained in a real-world setting demonstrate clinical benefits of IRd regimen in RRMM pts, which were achieved without negatively affecting QoL and with satisfactory symptom control in these heavily pretreated patients. IISR funded by Takeda Disclosures Ionova: BMS: Research Funding; Takeda: Research Funding. Vinogradova:Novartis: Honoraria, Research Funding.

Materialart: Online-Ressource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-134415

Sprache: Englisch

Verlag: American Society of Hematology

Publikationsdatum: 2020

ZDB Id: 1468538-3

ZDB Id: 80069-7

In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 5296-5296

Kurzfassung: There is a continued unmet medical need in pts with relapsed/refractory Hodgkin's lymphoma (RR HL). Curing HL pts who have refractory disease after salvage chemotherapy, who relapse after ASCT, or those who are not candidates for ASCT, remains a clinical challenge due to limited effective treatments. There are data available indicating that brentuximab vedotin (BV) brings considerable promise for the treatment of pts with RR HL. Information about BV treatment effectiveness and tolerability both from physician's and patient's perspective is worthwhile in this difficult patient population. We aimed to evaluate clinical and patient-reported outcomes in RR HL patients receiving BV as 〉 2nd treatment line. Here we report the outcomes with respect to clinical response, tolerability, quality of life (QoL) and symptoms after 3 mos of BV treatment. The total number of pts to be included in the multicenter observational real-world study is 70 pts with RR HL who received BV 1.8 mg/kg q3w till disease progression, intolerance toxicity of BV or refusal. Treatment response was assessed using RECIST criteria v. 1.0. Adverse events (AEs) were assessed in accordance with NCI CTCAE v. 4.03. For QoL assessment pts filled out RAND SF-36, for symptom assessment - ESAS questionnaire; also pts filled out PGIC scale for self-assessment of changes in their health. For QoL analysis paired t-test, Mann-Whitney test, Wilcoxon test and χ2 were used. The analysis was performed in the group of 55 pts RR HL (median age - 28 years, range 18-67, 54.5% males) who were involved in the study: 63.6% pts had advanced stage (III-IV) at diagnosis; ≥50% pts had B-symptoms (58.2%); 82% pts - ECOG 0-1. All the pts received a median of 3 previous treatment lines; among them 14 pts (25.5%) failed to ASCT in the past; half of pts were primary chemotherapy resistant (49%). Before BV treatment start QoL was dramatically worsened for all SF-36 scales (p 〈 0.05). All the pts experienced symptoms, 83.3% pts had moderate-to-severe symptoms. The most frequent ( 〉 70% pts) symptoms were drowsiness, tiredness, anxiety, and worse wellbeing. More than half pts had moderate-to-severe drowsiness,tiredness, depression, lack of appetite and worsened wellbeing before BV treatment start. After 3 mos of BV treatment objective response was registered in 55% pts with 27.5% complete response. Adverse events of grade I-II were reported in 8 pts (20%) and were consistent with known toxicities. Most common adverse events (≥10%) were increasing ALT and AST (each 4/8), peripheral neuropathy, fatigue, skin itch (each 3/8). Severe adverse event (III grade) not related with BV occurred in one patient (2.5%) - sepsis, respiratory insufficiency due to agranulocytosis (BV was temporary stopped). During BV treatment meaningful QoL improvement was revealed for all SF-36 scales (p 〈 0.05), excluding mental health. IQoLI significantly increased at 3 mos after treatment start as compared to baseline: 0.260 at baseline vs 0.390 at 3 mos (p 〈 0.001). Proportion of pts with significant Integral QoL Index (IQoLI) impairment dramatically decreased during treatment as compared to baseline: 60% before treatment vs 35% at 3 mos (χ2, p=0.05). The most pronounced meaningful improvement was revealed for role functioning scales (∆ 〉 20.0). The severity of the vast majority of symptoms excluding depression significantly decreased during 3 mos of treatment (p 〈 0.05). Total Symptom Score by ESAS significantly decreased at 3 mos after BV treatment start (35.8 vs 25.4, p=0.001). Also according to PGIC, 90% pts noted the improvement of their health. The first results obtained in this multicenter observational real world study demonstrate notable activity of BV as a treatment modality for RR HL. BV showed a safety profile consistent with known toxicities. BV treatment was accompanied with dramatic QoL improvement and significant decrease of symptom burden already after 3 mos of treatment. Evaluation of BV treatment outcomes both from physician's and patient's perspective may provide unique information which will be helpful in decision making for patients with RR HL. Disclosures Ionova: Takeda, BMS: Other: Principal Investigator of IISR, Research Funding. Baryakh:Takeda: Consultancy, Honoraria, Speakers Bureau.

Materialart: Online-Ressource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2019-121997

Sprache: Englisch

Verlag: American Society of Hematology

Publikationsdatum: 2019

ZDB Id: 1468538-3

ZDB Id: 80069-7

In: Terapevticheskii arkhiv, Consilium Medicum, Vol. 94, No. 7 ( 2022-08-12), p. 827-835

Kurzfassung: Aim. The primary objective of the interim analysis of the MULTISPECT study was to evaluate the short-term efficacy of the treatment and long-term outcomes in cohorts of primary and pretreated patients with multiple myeloma (MM) receiving treatment in actual clinical practice in various regions of the Russian Federation. Secondary objectives were a description of the main characteristics of patients; analysis of the most commonly used therapy regimens of the 1st and later lines and the sequence of their changes; evaluation of the response to therapy. Additional objectives included evaluation of the effect of the new COVID-19 coronavirus infection on the course of MM in patients. Materials and methods. The study is an observational retrospective-prospective multicenter cohort study. For its implementation, a structured database of patients with MM was used, provided by hematologists of the centers affiliated for the study. Results. The study included 1,294 patients (cohort 1 806, cohort 2 488). In both cohorts, patients aged 6069 years were in the majority. 3 lines of therapy (L1, L2, L3) were used for cohort 1; in cohort 2, the 4th line of therapy was also used in 2 patients. The therapy regimens were analyzed for 290 (22.41%) of all patients in the study. Responses to therapy were analyzed for 214 patients of cohort 1 and 109 patients of cohort 2. Autologous and allogeneic hematopoietic stem cell transplantations were carried out for a limited proportion of patients in both cohorts. At the end of the study and upon presentation of its results, the status of patients was the following: 96% of patients in cohort 1 and 89% in cohort 2 were alive. The therapy regimens in both cohorts were characterized by variability. The most commonly used regimens in each of the lines of therapy have been identified. The most used therapy regimen in patients with MM of both cohorts was the VCD-regime. Rd-regime in cohort 1 and RD-regime in cohort 2 were the second most frequent used regimens. In patients of both cohorts, the therapy regimens including Bortezomib were most often used. Conclusion. The variety of therapy regimens used to treat MM in actual clinical practice may be due to the factors of availability of new medicines and updated recommendations for the treatment of the disease. Further, in the context of this study, a more detailed analysis of the efficacy of certain therapy regimens in the 1st and later lines on progression free survival and overall survival of MM patients should be carried out.

Materialart: Online-Ressource

ISSN: 2309-5342 , 0040-3660

URL: Article

DOI: 10.26442/00403660.2022.07.201718

Sprache: Unbekannt

Verlag: Consilium Medicum

Publikationsdatum: 2022

In: Experimental and Molecular Pathology, Elsevier BV, Vol. 116 ( 2020-10), p. 104524-

Materialart: Online-Ressource

ISSN: 0014-4800

URL: Article

DOI: 10.1016/j.yexmp.2020.104524

Sprache: Englisch

Verlag: Elsevier BV

Publikationsdatum: 2020

ZDB Id: 1466769-1

In: Journal of Modern Oncology, Consilium Medicum, Vol. 24, No. 1 ( 2022-04-30), p. 80-88

Kurzfassung: Aim. To assess effectiveness and safety of Extimia BIOCAD (INN: empegfilgrastim) used to decrease the rate and duration of neutropenia, the rate of febrile neutropenia and infections that manifest in febrile neutropenia in patients with lymphoproliferative diseases who receive myelosuppressive therapy. Materials and methods. The paper presents the results of the second interim analysis of multicenter retrospective-and-prospective observational post-marketing study of effectiveness and safety of Extimia BIOCAD (INN: empegfilgrastim) in patients with lymphoproliferative diseases who receive cytotoxic therapy. The second stage of the interim analysis describes patient characteristics, therapy used in 221 patients with morphologically confirmed lymphoma who received one or more cycles of chemotherapy as part of LEGERITY study. The endpoints of interest included the rate of Grade 3/4 neutropenia in patients, after the first cycle of any therapy line; the rate of febrile neutropenia; the rate of Grade 3/4 infectious complications; the rate of antibacterial therapy prescriptions; and the assessment of the relative dose-intensity of received chemotherapy. Additionally, the incidence rate of all adverse drug reactions (ADRs) was assessed in patients who received at least one dose of the study drug; the incidence rate of all serious ADRs was assessed in patients who received at least one dose of the study drug; the incidence rate of Common Terminology Criteria for Adverse Events (CTCAE) 5.0 Grade 3/4 ADRs in patients who received at least one dose of the study drug; the rate of study drug discontinuations due to ADRs was also assessed. Results. As of the second interim analysis, LEGERITY included 221 patients with various indolent and aggressive lymphomas. Median age of the patients was 53 years (1982). A group of older patients (over 60 years of age) accounted for 34% of the study population. Patients received 1 injection of Extimia per chemotherapy cycle. Grade 3/4 neutropenia was registered in 6.7% (n=14) patients. Overall, all-grade neutropenia was reported in 21.4% (n=44) patients. Febrile neutropenia was reported in 2.9% cases. Severe infections and the use of antimicrobials were reported in no patients throughout the CT period and after each cycle of therapy. Most commonly reported adverse reactions included mild-to-moderate ossalgias (6.8%) and myalgias, back pain, and arthralgias (3.2%), that did not require pharmaceutical therapy. One (0.5%) patient had a severe adverse drug reaction a CTCAE 5.0 Grade 4 hypotension episode. Conclusion. Interim analysis results support high effectiveness and safety of the Russian original pegylated granulocyte colony-stimulating factor of empegfilgrastim (Extimia) in patients both with indolent and aggressive lymphomas. Real world evidence demonstrates a favourable safety and tolerability profile of empegfilgrastim in all age groups, including in the aging population. As of the moment of the interim analysis publication, the study is ongoing. Final conclusions on the safety and effectiveness of empegfilgrastim (Extimia) are to be drawn upon the study completion.

Materialart: Online-Ressource

ISSN: 1815-1442 , 1815-1434

URL: Article

DOI: 10.26442/18151434.2022.1.201493

Sprache: Unbekannt

Verlag: Consilium Medicum

Publikationsdatum: 2022

In: The Lancet Oncology, Elsevier BV, Vol. 22, No. 1 ( 2021-01), p. 142-154

Materialart: Online-Ressource

ISSN: 1470-2045

URL: Article

DOI: 10.1016/S1470-2045(20)30680-X

Sprache: Englisch

Verlag: Elsevier BV

Publikationsdatum: 2021

ZDB Id: 2049730-1

In: Pathobiology, S. Karger AG, Vol. 87, No. 6 ( 2020), p. 367-374

Kurzfassung: 〈 b 〉 〈 i 〉 Introduction: 〈 /i 〉 〈 /b 〉 There is some evidence suggesting a link between 〈 i 〉 BRCA1/2 〈 /i 〉 germline mutations and increased risk of gastric cancer. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Endoscopic screening for stomach malignancies was performed in 120 〈 i 〉 BRCA1 〈 /i 〉 mutation carriers in order to evaluate the probability of detecting the tumor disease. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 No instances of gastric cancer were revealed at the first visit. The analysis of atrophic changes performed by OLGA (Operative Link for Gastritis Assessment) criteria revealed that OLGA stages I–IV alterations were observed in 26 of 41 (63%) subjects aged & #x3e;50 years as compared to 29 of 79 (37%) in younger subjects ( 〈 i 〉 p 〈 /i 〉 = 0.007, χ 〈 sup 〉 2 〈 /sup 〉 test). One 〈 i 〉 BRCA1 〈 /i 〉 mutation carrier developed gastric cancer 4 years after the first visit for endoscopic examination. We performed next-generation sequencing analysis for this tumor and additional 4 archival gastric cancers obtained from 〈 i 〉 BRCA1/2 〈 /i 〉 mutation carriers. Somatic loss of the remaining 〈 i 〉 BRCA1/2 〈 /i 〉 allele was observed in 3 out of 5 tumors analyzed; all of these carcinomas, but none of the malignancies with the retained 〈 i 〉 BRCA1/2 〈 /i 〉 copy, showed chromosomal instability. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 Taken together, these data justify further studies on the relationships between the 〈 i 〉 BRCA1/2 〈 /i 〉 and gastric cancer.

Materialart: Online-Ressource

ISSN: 1015-2008 , 1423-0291

URL: Article

DOI: 10.1159/000511323

Sprache: Englisch

Verlag: S. Karger AG

Publikationsdatum: 2020

ZDB Id: 1483541-1

SSG: 12

In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 156-156

Kurzfassung: Introduction Daratumumab (DARA) is a human IgGκ anti-CD38 monoclonal antibody with a direct on-tumor and immunomodulatory mechanism of action. In combination with standard of care (SOC) regimens, DARA has consistently demonstrated a doubling of complete response (CR) rates, tripling of minimal residual disease (MRD)-negative rates, and reduction in the risk of progression or death by ≥50% vs SOC alone in relapsed/refractory MM and NDMM pts. In the prespecified interim analysis of ALCYONE, a phase 3 study of D-VMP versus VMP in transplant ineligible NDMM (Mateos MV, N Engl J Med 2018. 378[6]:518-528), significant progression-free survival (PFS) benefit (median not reached [NR] vs 18.1 mo; hazard ratio [HR], 0.50; P 〈 0.001) and a higher rate of MRD negativity (10-5 threshold: 22% vs 6%; P 〈 0.001) were observed without increased overall toxicity for D-VMP versus VMP after a median follow-up of 16.5 months. This report provides updated efficacy and safety findings from ALCYONE after 1 year of additional follow-up. Methods Pts were ≥65 years of age or ineligible for high-dose chemotherapy with autologous stem cell transplantation. Pts were randomized 1:1 to receive up to nine 6-week cycles of VMP (V 1.3 mg/m2 SC on Days 1, 4, 8, 11, 22, 25, 29, 32 [Cycle 1] and Days 1, 8, 22, and 29 [Cycles 2-9] ; M 9 mg/m2 PO and P 60 mg/m2 PO on Days 1-4 [Cycles 1-9]) with or without DARA (16 mg/kg IV QW for Cycle 1, Q3W for Cycles 2-9, and Q4W for Cycles 10+ until disease progression). PFS was the primary endpoint. PFS on the subsequent line of therapy (PFS2), overall response rate (ORR), CR or better rate, very good partial response (VGPR) or better rate, MRD-negative rate (10-5 threshold: clonoSEQ® V2.0, Adaptive), overall survival (OS), and safety were secondary endpoints. PFS2 was defined as the duration from randomization to progression on the next line of subsequent antimyeloma therapy or death, whichever occurred first. Results A total of 706 pts were randomized (350 D-VMP; 356 VMP). Median (range) age was 71 (40-93) years, with 29.9% being ≥75 years of age. Of the 616 pts evaluable for cytogenetic risk assessment via fluorescence in-situ hybridization/karyotyping, 84.1% had standard-risk and 15.9% had high-risk (del17p, t[14;16], and/or t[4;14] positive) disease. At the updated clinical cutoff date (June 12, 2018), all pts in both arms had either completed or discontinued from 9 treatment cycles of VMP, with 194 (56%) pts in the D-VMP arm remaining on the study to receive DARA monotherapy in Cycles 10+. After median follow-up of 27.8 months, median PFS was NR for D-VMP vs 19.1 months for VMP (HR, 0.43; 95% confidence interval [CI], 0.35-0.54; P 〈 0.0001; Figure). All prespecified subgroups showed a PFS benefit of D-VMP vs VMP, including pts ≥75 years of age (median: 32.2 mo vs 20.1 mo; HR, 0.51; 95% CI, 0.34-0.75). Significantly higher ORR and rates of deeper responses were observed for D-VMP vs VMP (Table). Median duration of response among responders was NR for D-VMP vs 21.1 months for VMP. Median PFS2 was NR in either arm (unstratified HR, 0.59; 95% CI, 0.43-0.82; P = 0.0013); 24-month PFS2 rates were 84.1% vs 78.5%, respectively. Updated MRD results will be presented. Grade 3/4 treatment-emergent adverse events (TEAEs; D-VMP/VMP) occurring in ≥10% of pts were neutropenia (39.9%/39.0%), thrombocytopenia (34.7%/37.9%), anemia (17.1%/19.8%), and pneumonia (12.4%/4.0%); grade 3/4 infection rates were 25.1% vs 14.7%, respectively. Among D-VMP pts who received D monotherapy (Cycles 10+; n = 278), 66 (23.7%) pts reported grade 3/4 TEAEs; the most common were anemia (3.6%), pneumonia (2.5%), neutropenia (1.8%), and thrombocytopenia (1.4%). Two pts in the D-VMP arm and 1 pt in the VMP arm discontinued treatment due to pneumonia, and treatment discontinuations due to infection occurred in 1.4% vs 1.7% for D-VMP vs VMP. Conclusions With 1 year of additional follow-up, the combination of DARA and VMP in transplant ineligible NDMM pts continues to demonstrate a significant PFS benefit, including in pts ≥75 years of age, and allows for maintenance of PFS benefit during the subsequent line of therapy. Improvements in duration and depth of response continue to be observed with D-VMP with longer follow-up. No new safety signals emerged following the addition of DARA to VMP, and grade 3/4 infections continue to be manageable with no notable increase in rates. These results continue to support the use of D-VMP in the first line of treatment in transplant ineligible NDMM. Disclosures Dimopoulos: Amgen: Honoraria; Bristol-Myers Squibb: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Takeda: Honoraria. Mateos:GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Cavo:Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees. Suzuki:Sanofi Aventis: Consultancy, Honoraria; Ono: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; SRL.Inc: Employment. Jakubowiak:Bristol-Myers Squibb: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Adaptive Biotechnologies: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; SkylineDx: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Knop:Takeda: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Doyen:Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees. Lucio:Janssen: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau. Cook:Chugai: Honoraria; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Jazz: Honoraria; YAkeda: Honoraria; Amgem: Honoraria. Grosicki:Affimed: Research Funding. Garg:Novartis: Other: travel support, Research Funding; Janssen: Honoraria; Takeda: Other: Travel Grant; Amgen: Honoraria, Other: Travel Support. Chiu:Janssen Research & Development, LLC: Employment. Wang:Janssen Research & Development, LLC: Employment. Kudva:Janssen Research & Development: Employment. Kobos:Janssen Research & Development: Employment. Wroblewski:Janssen Research & Development: Employment. Qi:Janssen Research & Development, LLC: Employment. San-Miguel:Celgene: Honoraria; Sanofi: Honoraria; Novartis: Honoraria; BMS: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Roche: Honoraria. Bladé:Janssen: Honoraria.

Materialart: Online-Ressource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2018-156

Sprache: Englisch

Verlag: American Society of Hematology

Publikationsdatum: 2018

ZDB Id: 1468538-3

ZDB Id: 80069-7

In: Pediatric Blood & Cancer, Wiley, Vol. 67, No. 5 ( 2020-05)

Kurzfassung: Inflammatory myofibroblastic tumors (IMTs) are exceptionally rare neoplasms, which are often driven by rearranged tyrosine kinases. Methods This study considered 33 consecutive patients with IMT (median age, 6.6; age range, 0.6‐15.8 years). RNA and cDNA were successfully obtained in 29 cases. The molecular analysis included sequential tests for 5′/3′‐end unbalanced gene expression, variant‐specific PCR, and next‐generation sequencing (NGS). Results 5′/3′‐end unbalanced ALK expression was revealed in 15/29 (52%) IMTs. Strikingly, all these tumors demonstrated high amount of ALK protein detected by immunohistochemistry. Variant‐specific PCR was capable of identifying the type of ALK rearrangement in 11/15 IMTs with 5′/3′‐end unbalanced ALK expression. The remaining four tumors were analyzed by NGS; two known and two novel ( CLTC ‐ins6del84‐ ALK and EEF1G ‐ ALK ) ALK rearrangements were detected. Five IMTs demonstrated 5′/3′‐end unbalanced ROS1 expression, and all these tumors carried TFG‐ROS1 fusion. Nine tumors, which were negative for 5′/3′‐end unbalanced ALK/ROS1 expression, were subjected to further analysis. Variant‐specific PCR revealed two additional tumors with gene rearrangements ( TFG‐ROS1 and ETV6‐NTRK3 ). The remaining seven IMTs were tested by NGS; single instances of TFG‐ROS1 and novel SRF‐PDGFRb translocations were detected. Conclusions Twenty‐four of 29 IMTs (83%) were shown to have druggable rearrangements involving tyrosine kinases, 20 of these 24 gene fusions were detectable by simple and inexpensive PCR assay, which is based on the detection 5′/3′‐end unbalanced gene expression.

Materialart: Online-Ressource

ISSN: 1545-5009 , 1545-5017

URL: Issue

URL: Article

DOI: 10.1002/pbc.v67.5

DOI: 10.1002/pbc.28220

Sprache: Englisch

Verlag: Wiley

Publikationsdatum: 2020

ZDB Id: 2130978-4