Kooperativer Bibliotheksverbund

In: Blood Cancer Journal, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2023-01-04)

Abstract: Mass spectrometry (MS) is a promising tool for monitoring monoclonal protein in plasma cell dyscrasias. We included 480 transplant-eligible newly-diagnosed multiple myeloma (MM) patients from the GMMG-MM5 trial (EudraCT No. 2010-019173-16) and performed a retrospective MS analysis at baseline (480 patients) and at the pre-defined, consecutive time points after induction (444 patients), prior to maintenance (305 patients) and after one year of maintenance (227 patients). We found that MS negativity was significantly associated with improved progression-free survival (PFS) even in patients with complete response (CR) at all investigated follow-up time points. The prognostic impact was independent of established risk factors, such as the revised International Staging System. Combining MS and baseline cytogenetics improved the prediction of outcome: MS-positive patients with high-risk cytogenetics had a dismal PFS of 1.9 years (95% confidence interval [CI] : 1.6–2.3 years) from the start of maintenance. Testing the value of sequential MS prior to and after one year of maintenance, patients converting from MS positivity to negativity had an excellent PFS (median not reached) while patients converting from MS negativity to positivity progressed early (median 0.6 years, 95% CI: 0.3-not reached). Among patients with sustained MS positivity, the baseline high-risk cytogenetic status had a significant impact and defined a group with poor PFS. Combining minimal residual disease (MRD) in the bone marrow and MS allowed the identification of double negative patients with a favorable PFS (median 3.33 years, 95% CI: 3.08-not reached) and no overall survival events. Our study provides strong evidence that MS is superior to conventional response monitoring, highlighting the potential of MS to become a new standard. Our data indicate that MS should be performed sequentially and combined with baseline disease features and MRD to improve its clinical value. Clinical Trials Register: EudraCT No. 2010-019173-16

Type of Medium: Online Resource

ISSN: 2044-5385

URL: Article

DOI: 10.1038/s41408-022-00772-9

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2023

detail.hit.zdb_id: 2600560-8

In: Blood, American Society of Hematology, Vol. 141, No. 14 ( 2023-04-06), p. 1685-1690

Abstract: Activating BRAF mutations are found in a small subset of patients with newly diagnosed multiple myeloma, but prevalence increases in late-stage, refractory disease, and the mutations are associated with adverse outcome. This prospective single-arm, open-label, multicenter phase 2 trial assessed the efficacy and safety of combined BRAF/MEK inhibition, using encorafenib and binimetinib, in patients with relapsed/refractory multiple myeloma (RRMM) carrying a BRAFV600E mutation. Patients received 450 mg encorafenib once daily and binimetinib 45 mg twice daily. The primary end point was the overall response rate achieved within the first year after start of treatment according to International Myeloma Working Group criteria. Twelve RRMM patients with a median of 5 prior lines of therapy were enrolled. The overall response rate was 83.3%, with 10 patients achieving at least a partial response. The median progression-free survival was 5.6 months, and overall survival was 55% at 24 months. Emerging resistance to therapy was driven by RAS mutations and structural variants involving the BRAF locus. This is the first prospective clinical trial to demonstrate that combined BRAF/MEK inhibition is highly effective in patients with BRAFV600E-mutated RRMM, and it represents a successful targeted precision medicine approach in this disease. This trial was registered at www.clinicaltrials.gov as #NCT02834364.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.2022017789

Language: English

Publisher: American Society of Hematology

Publication Date: 2023

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 14-14

Abstract: Introduction: Despite improvements in the prognosis of multiple myeloma (MM), most patients ultimately relapse and undergo multiple lines of therapy. Due to the immunocompromising effects of virtually all anti-myeloma agents as well as the disease itself, infections are a frequent complication during therapy and the most important cause of mortality in patients with MM. Establishment of clear predictors of infectious complications, especially under therapy with novel agents, is therefore of major clinical importance to identify patients at risk and to guide anti-infective prophylaxis. Methods: In this prospective, observational cohort study we examined the development of CD4+ T-cell numbers during anti-myeloma therapies which were based on the novel agents daratumumab, carfilzomib, elotuzumab, or pomalidomide and their impact on infectious complications in 96 patients with relapsed/refractory MM (median prior lines of therapy: 2 [1-13], median age: 70 years of age [42-90] ). Data on infectious events including CTC-AE severity grading, antimicrobial prophylaxis strategies and vaccination status was collected before start of therapy, after 3 months and after 6 months of therapy. Flow cytometry was used to identify T-cell subsets at all three timepoints. Results: Before start of therapy, 25 patients (26%) had CD4+ cell counts & lt; 200/µl, 75 patients (78%) had CD4+ cell counts & lt; 500/µl. In a multivariate linear regression model the number of previous lines of therapy had a significant negative impact on CD4+-cell numbers at start of relapse therapy (p=0.03), whereas age and active therapy within in the last 6 months did not. With regard to relapse therapy, both pomalidomide and carfilzomib led to a significant reduction in CD4+ cell count after 3 months of therapy (p=0.03 and p= 0.04, resp.) in a multivariate linear regression model. This effect was not noticeable in treatments based on daratumumab. In a multivariate logistic regression analysis with regard to the occurrence of infections ≥ CTC II° within the first 3 cycles of therapy, CD4+ cell count at start of relapse therapy was the only predictor with borderline statistical significance (p=0.06). Conclusions: A significant proportion of patients with relapsed refractory MM show a severe reduction of CD4+ T-cells already at start of relapse therapy, especially after multiple lines of therapy. CD4+ cell count at start of relapse therapy might indicate an increased risk of infectious complications. Additional studies with a larger number of patients are warranted to further elucidate the impact of CD4+ cell count at start of relapse therapy as a predictor of infectious complications in MM and whether it might serve to better identify patients at risk of infectious complications and steer antimicrobial prophylaxis strategies. Disclosures John: Proteona: Research Funding. Mueller-Tidow:Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Daiichi Sankyo: Research Funding; Jose-Carreras-Siftung: Research Funding; Bayer AG: Research Funding; BiolineRx: Research Funding; Wilhelm-Sander-Stiftung: Research Funding; BMBF: Research Funding; Deutsche Krebshilfe: Research Funding; Janssen-Cilag Gmbh: Membership on an entity's Board of Directors or advisory committees; Deutsche Forschungsgemeinschaft: Research Funding. Jordan:priME Oncology: Speakers Bureau; Shire: Membership on an entity's Board of Directors or advisory committees; G1 Therapeutics: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Voluntis: Membership on an entity's Board of Directors or advisory committees; Pomme-med: Speakers Bureau; Hexal: Speakers Bureau; Merck: Membership on an entity's Board of Directors or advisory committees; Merck Sharp & Dome: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; medupdate: Speakers Bureau; Helsinn: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Tesaro: Membership on an entity's Board of Directors or advisory committees; ClinSolResearch: Membership on an entity's Board of Directors or advisory committees; Riemser: Research Funding, Speakers Bureau; Amgen: Speakers Bureau; Kreussler: Membership on an entity's Board of Directors or advisory committees; art-tempi: Speakers Bureau. Goldschmidt:Dietmar-Hopp-Foundation: Other: Grants and/or provision of Investigational Medicinal Product:; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product:, Research Funding; Incyte: Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product:, Research Funding; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; Johns Hopkins University: Other: Grants and/or provision of Investigational Medicinal Product; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product:, Research Funding; Novartis: Honoraria, Research Funding; Mundipharma GmbH: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Molecular Partners: Research Funding; Merck Sharp and Dohme (MSD): Research Funding; University Hospital Heidelberg, Internal Medicine V and National Center for Tumor Diseases (NCT), Heidelberg, Germany: Current Employment; GlaxoSmithKline (GSK): Honoraria; Adaptive Biotechnology: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product, Research Funding; Chugai: Honoraria, Other: Grants and/or provision of Investigational Medicinal Product:, Research Funding. Raab:Heidelberg Pharma: Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-136686

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Cells, MDPI AG, Vol. 11, No. 15 ( 2022-08-08), p. 2462-

Abstract: We recently derived and validated a serum-based microRNA risk score (miR-score) which predicted colorectal cancer (CRC) occurrence with very high accuracy within 14 years of follow-up in a large population-based cohort. Here, we aimed to assess and compare the distribution of the miR-score among participants of screening colonoscopy at various stages of colorectal carcinogenesis. MicroRNAs (miRNAs) were profiled by quantitative-real-time-polymerase-chain-reaction in the serum samples of screening colonoscopy participants with CRC (n = 52), advanced colorectal adenoma (AA, n = 100), non-advanced colorectal adenoma (NAA, n = 88), and participants free of colorectal neoplasms (n = 173). The mean values of the miR-score were compared between groups by the Mann–Whitney U test. The associations of the miR-score with risk for colorectal neoplasms were evaluated using logistic regression analyses. MicroRNA risk scores were significantly higher among participants with AA than among those with NAA (p = 0.027) and those with CRC (p = 0.014), whereas no statistically significant difference was seen between those with NAA and those with no colorectal neoplasms (p = 0.127). When comparing adjacent groups, miR-scores were inversely associated with CRC versus AA and positively associated with AA versus NAA [odds ratio (OR), 0.37 (95% confidence interval (CI), 0.16–0.86) and OR, 2.22 (95% CI, 1.06–4.64) for the top versus bottom tertiles, respectively]. Our results are consistent with the hypothesis that a high miR-score may be indicative of an increased CRC risk by an increased tendency of progression from non-advanced to advanced colorectal neoplasms, along with a change of the miR-patterns after CRC manifestation.

Type of Medium: Online Resource

ISSN: 2073-4409

URL: Article

DOI: 10.3390/cells11152462

Language: English

Publisher: MDPI AG

Publication Date: 2022

detail.hit.zdb_id: 2661518-6

In: The Lancet Haematology, Elsevier BV, Vol. 11, No. 2 ( 2024-02), p. e101-e113

Type of Medium: Online Resource

ISSN: 2352-3026

URL: Article

DOI: 10.1016/S2352-3026(23)00366-6

Language: English

Publisher: Elsevier BV

Publication Date: 2024

In: Leukemia, Springer Science and Business Media LLC, Vol. 35, No. 12 ( 2021-12), p. 3636-3636

Type of Medium: Online Resource

ISSN: 0887-6924 , 1476-5551

URL: Article

DOI: 10.1038/s41375-021-01357-4

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2021

detail.hit.zdb_id: 2008023-2

In: British Journal of Surgery, Oxford University Press (OUP), Vol. 108, No. 12 ( 2021-12-01), p. 1448-1464

Abstract: This study aimed to determine the impact of pulmonary complications on death after surgery both before and during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Methods This was a patient-level, comparative analysis of two, international prospective cohort studies: one before the pandemic (January–October 2019) and the second during the SARS-CoV-2 pandemic (local emergence of COVID-19 up to 19 April 2020). Both included patients undergoing elective resection of an intra-abdominal cancer with curative intent across five surgical oncology disciplines. Patient selection and rates of 30-day postoperative pulmonary complications were compared. The primary outcome was 30-day postoperative mortality. Mediation analysis using a natural-effects model was used to estimate the proportion of deaths during the pandemic attributable to SARS-CoV-2 infection. Results This study included 7402 patients from 50 countries; 3031 (40.9 per cent) underwent surgery before and 4371 (59.1 per cent) during the pandemic. Overall, 4.3 per cent (187 of 4371) developed postoperative SARS-CoV-2 in the pandemic cohort. The pulmonary complication rate was similar (7.1 per cent (216 of 3031) versus 6.3 per cent (274 of 4371); P = 0.158) but the mortality rate was significantly higher (0.7 per cent (20 of 3031) versus 2.0 per cent (87 of 4371); P  & lt; 0.001) among patients who had surgery during the pandemic. The adjusted odds of death were higher during than before the pandemic (odds ratio (OR) 2.72, 95 per cent c.i. 1.58 to 4.67; P  & lt; 0.001). In mediation analysis, 54.8 per cent of excess postoperative deaths during the pandemic were estimated to be attributable to SARS-CoV-2 (OR 1.73, 1.40 to 2.13; P  & lt; 0.001). Conclusion Although providers may have selected patients with a lower risk profile for surgery during the pandemic, this did not mitigate the likelihood of death through SARS-CoV-2 infection. Care providers must act urgently to protect surgical patients from SARS-CoV-2 infection.

Type of Medium: Online Resource

ISSN: 0007-1323 , 1365-2168

URL: Article

DOI: 10.1093/bjs/znab336

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2021

detail.hit.zdb_id: 2006309-X

In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 44-45

Abstract: Introduction: The treatment of patients (pts) with rrMM remains challenging and response is often limited in depth and duration. In contrast to many other malignant diseases, targeted therapy in MM is hampered by the limited number of actionable targets. Activating mutations of BRAF have been found in 2-4% of newly diagnosed MM and in up to 8% of rrMM. Several case reports have reported clinical efficacy of downstream pathway inhibition in MM. This phase II trial is evaluating the safety and efficacy of combined BRAF/MEK inhibition in rrMM pts with BRAF V600E mutation. Aims: The primary objective of this study was to demonstrate the therapeutic efficacy of encorafenib in combination with binimetinib. The primary endpoint was the overall response rate (ORR), defined as best response within 1 year of treatment. Main secondary endpoints included progression-free survival (PFS) and duration of response. Safety analyses included all adverse events (AEs) with those of grade 1/2 only being assessed further if considered to be related to study medications by the investigator. Methods: A total of 15 pts with rrMM who have failed at least 2 prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMID), were planned to be enrolled in this open-label phase II multicenter trial. Key inclusion criteria were presence of a BRAF V600E/K mutation confirmed by both mutation-specific immunohistochemistry (IHC) and next-generation sequencing in more than 50% of MM cells. Exclusion criteria included plasma cell leukemia, CNS involvement, cardiac dysfunction, or a history of retinal vein occlusion. Pts received encorafenib 450mg p.o. daily and binimetinib 45mg p.o. twice daily. Responses were assessed using IMWG 2016 criteria. The primary endpoint was analyzed by testing the one-sided null hypothesis of ORR & lt;= 20% using a one-sided binomial test at a significance level of 5%. Exploratory biomarker assessments include cytogenetics, genomic analysis (WGS, RNAseq) and phospho-IHC. Results: As of July 2020, 12 pts have been enrolled and were evaluable for safety and 11 pts were evaluable for response as 1 pt had just completed cycle 1 with confirmation of response pending at the time of data lock. Subtypes of MM were IgG in 6 pts, IgA in 2 pts, and Bence Jones in 4 pts. Pts had received a median of 5 prior lines of therapy (range 2-14). All pts had failed previous treatment with both a PI and an IMID and in addition carfilzomib, pomalidomid, and/or anti-CD38 antibodies in 8/4/6 pts, respectively. The study already reached its primary endpoint. The ORR was 82% (lower limit of the 95% CI 56.4%, one-sided exact binomial test, p & lt;0.0001) with 9/11 pts achieving partial response (PR) or better, 6/11 pts had at least a very good partial response (VGPR, 55%) and 3 pts reached (near) complete response (nCR/CR, 27%). Responses occurred rapidly with 8/11 pts achieving at least a PR or better already after cycle 1. PFS remains immature and will be reported at the conference. Duration of response exceeding 1 year has been observed in individual pts. Adverse events of all grades, assessed to be at least possibly related to a study drug, occurred in 9/12 pts and included blurred vision, macula edema, cramps, arthralgia, diarrhea, skin rash, and decreased left ventricular function. Grade 3 or 4 AEs irrespective of causality occurring in more than 1 pt were reported in 8 pts with anemia, hypertension and thrombocytopenia (3/ 3/ 2 pts, respectively). SAEs were reported in 2 pts, respiratory tract infection in both pts and tooth decay in 1 pt that was not related to the study medication. No deaths occurred while on treatment or within 30 days of the end of treatment. Preliminary results of biomarker assessments reveal new RAS mutations and amplification of the BRAF locus at the time of relapse while on study treatment as potential markers of resistance. Analysis of pharmacodynamic markers by phospho-IHC reveals suppression of BRAF/MEK signaling at cycle 1 / day 28 and restoration of expression at the time of relapse. Conclusion: Targeting activating BRAF mutations in rrMM by combining the BRAF inhibitor, encorafenib, and the MEK inhibitor, binimetinib, induces rapid and deep responses in the majority of pts. No new safety signal has been observed when compared to prior reports on these compounds. The study reached its primary endpoint with fewer pts than expected. The primary efficacy and safety analysis will be presented at the conference. Disclosures Raab: Janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Heidelberg Pharma: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Scheid:BMS: Honoraria; Amgen: Honoraria; Novartis: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Besemer:GSK: Honoraria; Janssen: Honoraria. Metzler:Janssen: Consultancy; Amgen: Consultancy; Takeda: Consultancy; GSK: Consultancy; BMS: Consultancy. Khandanpour:Astra Zeneca: Research Funding; Sanofi: Consultancy; Janssen: Consultancy; Amgen: Consultancy; Celgene: Consultancy. Trautmann-Grill:Janssen: Consultancy; Celgene: Consultancy; Sanofi: Consultancy; Takeda: Consultancy, Honoraria; GSK: Consultancy; BMS: Honoraria. Goldschmidt:Mundipharma GmbH: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck Sharp and Dohme (MSD): Research Funding; Chugai: Honoraria, Other: Grants and/or provision of Investigational Medicinal Product:, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product:, Research Funding; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product:, Research Funding; University Hospital Heidelberg, Internal Medicine V and National Center for Tumor Diseases (NCT), Heidelberg, Germany: Current Employment; GlaxoSmithKline (GSK): Honoraria; Adaptive Biotechnology: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product:, Research Funding; Novartis: Honoraria, Research Funding; Molecular Partners: Research Funding; Incyte: Research Funding; Johns Hopkins University: Other: Grants and/or provision of Investigational Medicinal Product; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; Dietmar-Hopp-Foundation: Other: Grants and/or provision of Investigational Medicinal Product:. Weisel:Abbvie: Consultancy, Honoraria; Adaptive: Consultancy, Honoraria; GlaxoSmithKline: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. OffLabel Disclosure: Encorafenib and Binimetinib in BRAF V600E mutant multiple myeloma

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-142600

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 486-486

Abstract: Background: Treatment regimens including a proteasome inhibitor, immunomodulating agent and a monoclonal antibody (moAb) play an emerging role in the treatment of newly-diagnosed multiple myeloma (NDMM). This multicenter phase III trial of the German-speaking Myeloma Multicenter Group (GMMG HD6) investigated the addition of the anti-SLAMF7 moAb elotuzumab to lenalidomide / bortezomib / dexamethasone (RVd) in induction and consolidation therapy as well as to lenalidomide maintenance treatment in transplant-eligible NDMM. Patients and Methods: Patients were equally randomized into four treatment arms, stratified by International Staging System (ISS). Treatment consisted of four 21-day cycles of RVd (arms A1/A2) or elotuzumab-RVd (arms B1/B2) induction therapy, respectively. High-dose melphalan (HDM) and autologous blood stem cell transplantation (ASCT) were followed by two 21-day cycles of RVd or elotuzumab-RVd consolidation and lenalidomide or elotuzumab-lenalidomide maintenance for two years (arms A1/B1 vs. A2/B2). Primary objective of the trial was determination of the best of four treatment strategies regarding progression-free survival (PFS) from randomization. Secondary endpoints included overall survival (OS), response rates and safety. Results: Between 06/2015 and 09/2017, 564 patients were included in the trial. The evaluable intention-to-treat (ITT) and safety population comprised 559 and 555 patients (A1: n=139/137; A2: n=141/138; B1: n=137/138; B2: n=142/142). Median age at randomization was 59 (range 27-70) years. Baseline characteristics were well balanced between the four treatment arms. Four cycles of induction therapy were completed by 517 patients (92.5% of ITT). At least one HDM/ASCT was applied in 495 (88.6%), of which 116 patients (20.8%) received tandem HDM/ASCT. Consolidation and maintenance therapy were initiated in 469 (83.9%) and 454 (81.2%) patients, respectively. Rates of very good partial response or better (≥VGPR) prior to start of consolidation therapy were 78.9%, 78.2%, 81.5% and 80.7% in arms A1, A2, B1 and B2, respectively (p=0.95). With a median follow-up time of 49.8 months, PFS was not significantly different between the four treatment arms (adjusted log-rank p value stratified by ISS, p=0.86; primary endpoint). OS was similar in all treatment arms (stratified log-rank p=0.43). 3-year PFS/OS rates are 68.8%/89.4%, 68.5%/89.1%, 66.2%/92.5% and 67.2%/89.7% in arm A1, A2, B1 and B2, respectively. Multivariate analyses including age, sex, ISS stage, performance status, serum lactate dehydrogenase level, renal impairment at diagnosis, adverse cytogenetics (del17p, t[4;14] and t[14;16] ) and treatment arms identified ISS stages II and III (hazard ratio [HR]=1.42/2.04, 95% conf idence interval [95% CI]= 1.00-2.02/1.36-3.07, p=0.048/ & lt;0.001) and adverse cytogenetics (HR=1.63, 95% CI: 1.19-2.25, p=0.003) as significant predictors for shortened PFS. On induction, consolidation and maintenance treatment, at least one (serious) adverse event (grade ≥3 for all AE or ≥2 for infections and infestations, neuropathy, cardiac disorders and thromboembolic events, and any grade for serious AE) occurred in 95.6%, 91.3%, 92.8% and 89.4% of patients in arm A1, A2, B1 and B2, respectively (p=0.25). Most common system organ classes (SOCs) were "infections and infestations", "neurological disorders", "blood and lymphatic system disorders", and "investigations" with no significant differences between the four treatment arms (p=0.39/0.64/0.13/0.42). Overall AE/SAE during lenalidomide vs. elotuzumab-lenalidomide maintenance were comparable (A1/B1: 65.5% vs. A2/B2: 66.4%,p=0.86), though SOC "infections and infestations" was increased in the elotuzumab-lenalidomide arms (A1/B1: 42.9% vs. A2/B2: 51.4%, p=0.05). Conclusions: This is the first phase III trial evaluating elotuzumab in patients with transplant-eligible NDMM. The addition of elotuzumab to RVd induction/consolidation therapy and lenalidomide maintenance did not result in improved PFS or OS. This is in line with previous reports from the ELOQUENT-1 and SWOG-1211 trials, investigating elotuzumab in non-transplant-eligible and high-risk NDMM, while elotuzumab-based combination therapies are effective in relapsed MM (ELOQUENT-2/-3 trials). Further analyses to identify potential subgroups that benefit from elotuzumab-based treatment in our trial are ongoing. Disclosures Goldschmidt: Incyte: Research Funding; BMS: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Celgene: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Chugai: Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; GSK: Honoraria; Janssen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Johns Hopkins University: Other: Grant; Molecular Partners: Research Funding; MSD: Research Funding; Mundipharma: Research Funding; Novartis: Honoraria, Research Funding; Dietmar-Hopp-Foundation: Other: Grant; Sanofi: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Takeda: Consultancy, Research Funding; Adaptive Biotechnology: Consultancy; Amgen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding. Mai: Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations and expenses, Research Funding; Glaxo Smith Kline: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations and expenses, Research Funding; Celgene / BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations and expenses, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations and expenses, Research Funding. Besemer: GSK: Honoraria; Janssen: Honoraria; Takeda: Honoraria. Haenel: Jazz: Consultancy, Honoraria; GSK: Consultancy; Bayer Vital: Honoraria; Takeda: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Amgen: Consultancy; Celgene: Consultancy, Honoraria. Fenk: Janssen: Honoraria; Amgen: Honoraria; GSK: Honoraria; Takeda: Honoraria; BMS/Celgene: Honoraria. Munder: Janssen: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Abbvie: Consultancy; Takeda: Consultancy, Honoraria; Amgen: Honoraria; Sanofi: Consultancy; GSK: Consultancy; Incyte: Research Funding. Dürig: Celgene: Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Hose: LamKap Bio: Consultancy, Current Employment; BMS: Research Funding. Scheid: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Schroers: BMS/Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Takeda: Honoraria. Metzler: GSK: Consultancy; Amgen: Consultancy; Janssen: Consultancy; AstraZeneca: Consultancy; Pfizer: Consultancy; Sanofi: Consultancy; BMS: Consultancy; Takeda: Consultancy. Schieferdecker: Sebia: Consultancy. Mahlberg: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria; BMS: Honoraria; GSK: Honoraria. Graeven: Amgen: Honoraria; Sanofi Aventis: Honoraria; Celgene: Honoraria, Research Funding; Johnson & Johnson: Honoraria; Astra Zeneca: Honoraria; MSD: Consultancy; Boehringer Ingelheim: Honoraria; BMS: Honoraria; Fujifilm: Honoraria; Roche: Research Funding; Gilead: Research Funding; Ipsen Bioscience: Research Funding; MacroGenics: Research Funding. Martens: Celgene: Consultancy; Sanofi-Aventis: Consultancy. Weisel: Adaptive Biotechnologies: 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, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy; Novartis: Honoraria; Pfizer: Honoraria. Raab: Roche: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees. Salwender: Takeda: Honoraria; Sanofi: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; GlaxoSmithKline: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Oncopeptides: Honoraria; Chugai: Honoraria; Amgen: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; AbbVie: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Janssen-Cilag: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Bristol-Myers Squibb/Celgene: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Pfizer: Honoraria. OffLabel Disclosure: Lenalidomide and ELotuzumab in first line therapy prior to autologous stem cell transplantation, Elotuzumab in maintenance after autologous transplantation.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2021-147323

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Frontiers in Oncology, Frontiers Media SA, Vol. 13 ( 2023-4-21)

Abstract: Infections are a leading cause of morbidity and mortality in patients with multiple myeloma (MM). Methods To examine the effects of modern second-generation novel agent therapy on immune cell subsets, in particular CD4+-T-cells, and infectious complications in patients with relapsed/refractory MM (RRMM), we conducted a prospective cohort study in 112 RRMM patients. Results Substantially decreased CD4+-T-cells & lt;200/µl before initiation of relapse therapy were detected in 27.7% of patients and were associated with a higher number of previous lines of therapy. Relapse therapy with carfilzomib or pomalidomide showed a significant further decrease of CD4+-T-cells. All novel agents led to a significant decrease of B-cell counts. Overall, infections were frequent with 21.3% of patients requiring antibacterial therapy within the first 3 months of relapse therapy, 5.6% requiring hospitalization. However, in the setting of standard antimicrobial prophylaxis in RRMM patients with very low CD4+-T-cells, no significant association of CD4+T-cell count and an increased risk of infection could be detected. Discussion Our findings imply that reduced CD4+-T-cell numbers and infections are common in patients with RRMM. We also demonstrate an association with the number of previous therapies and certain substances suggesting an increased need for personalized prophylaxis strategies for opportunistic infections in this patient cohort.

Type of Medium: Online Resource

ISSN: 2234-943X

URL: Article

URL: Article

DOI: 10.3389/fonc.2023.1078725

DOI: 10.3389/fonc.2023.1078725.s001

Language: Unknown

Publisher: Frontiers Media SA

Publication Date: 2023

detail.hit.zdb_id: 2649216-7