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  • American Society of Hematology  (2)
  • Abildgaard, Niels  (2)
  • 1
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 601-601
    Kurzfassung: Background: Salvage autologous stem cell transplantation (ASCT) is used in selected patients with relapsed multiple myeloma after up-front ASCT. However, there are limited data on the optimal induction therapy before salvage ASCT. There is strong support for the use of maintenance therapy after upfront ASCT in newly diagnosed multiple myeloma whereas data on maintenance therapy after salvage ASCT are sparse. The Nordic Myeloma Study Group (NMSG) initiated the CARFI trial (NCT02572492), an open randomized phase II study, to investigate the efficacy and safety of carfilzomib as part of induction and conditioning in salvage ASCT and to evaluate the role of carfilzomib/dexamethasone maintenance after salvage ASCT. Methods: Patients with first relapse after up-front ASCT were treated with an induction regime containing four cycles of CAR-CY-DEX (iv carfilzomib 20 mg/sqm → 36 mg/sqm on days 1, 2, 8, 9, 15 and 16, tablet cyclophosphamide 300 mg/sqm on days 1, 8 and 15 and tablet dexamethasone 20 mg on days 1, 2, 8, 9, 15 and 16 in each 28-days cycle). The subsequent conditioning regimen contained iv carfilzomib 27 mg/sqm on day -2 and -1, and iv melphalan 200 mg/sqm on day -2. The patients had not received any maintenance therapy after upfront ASCT. Two months after ASCT patients were randomized (1:1) to observation or maintenance therapy with iv carfilzomib 27 mg/sqm → 56 mg/sqm every second week and tablet dexamethasone 20 mg every second week. The randomization was stratified according to relapse 1 - 2 year or & gt; 2 years after up-front ASCT, ISS stage and standard versus high-risk cytogenetics. Primary endpoint was comparison of time to progression (TTP) after up-front ASCT and TTP after salvage ASCT with CAR-CY-DEX induction. Another primary endpoint was to compare TTP between carfilzomib-dexamethasone maintenance and observation in patients treated with salvage ASCT. Results: 200 patients were enrolled in the study and 32 of these went off study during the induction and after ASCT. The remaining 168 patients were randomized to carfilzomib-dexamethasone (82 patients) or observation (86 patients). The median age was 62 (interquartile range: 56; 66) years and the median follow-up from time of inclusion was 20.1 (14.1 - 27.6) months. The median TTP after up-front ASCT was 33.2 (31.0-37.8) months compared with 28.1 (24.9-31.5) months after salvage ASCT. The two groups randomised to maintenance therapy or observation were balanced regarding age, time from myeloma diagnosis, treatment at diagnosis, performance status, ISS stage and high-risk cytogenetics (Table 1). The median TTP from randomisation was 28.8 (95% CI: 24.4-NR) months in the maintenance group and 18.5 (95% CI: 14.3-22.0) months in the observation group (hazard ratio 0.42 (95% CI: 0.26-0.68, P = 0.0003)) (Figure I). For the maintenance group TTP from inclusion was 35.4 (30.9-NR) months compared with TTP of 31.3 (29.4-37.8) months (P = 0.71) after up-front ASCT for these patients. A total of 53 serious adverse events (SAE) were reported in 25 patients on carfilzomib-dexamethasone maintenance and 33 SAEs in 21 patients in the observation group. The majority of the SAEs were infections; 39 in the maintenance group and 25 in the observation group, divided into viral infection (10 versus 3), septicemia (2 versus 0) and pneumonia (12 versus 7). Three SAEs classified as cardiac-pulmonary were observed in the maintenance group (syncope, atrial fibrillation and pulmonary embolism) in contrast to three in the observation group (atrial fibrillation and dyspnea(2)). Conclusion: In this randomized phase 2 trial, maintenance therapy with carfilzomib and dexamethasone prolonged median TTP with approximately 10 months following salvage ASCT in multiple myeloma. The difference between TTP after upfront ASCT and TTP after salvage ASCT with carfilzomib based induction therapy was small which supports the use of salvage ASCT followed by maintenance in selected patients at first relapse. Disclosures Remes: Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees, Other: Congress Support; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Congress Support; Amgen: Other: Congress Support; Celgene: Other: Congress Support; Sanofi: Other: Congress Support. Schjesvold:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; 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; Novartis: Honoraria; MSD: 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; SkyliteDX: Honoraria; Oncopeptides: Membership on an entity's Board of Directors or advisory committees. Abildgaard:Amgen: Research Funding; Celgene: Research Funding; Janssen: Research Funding; Takeda: Research Funding. Vangsted:Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria; Jansen: Honoraria. Blimark:Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2019
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 1638-1638
    Kurzfassung: Background: The severe, acute respiratory syndrome, coronavirus 2 (SARS-CoV-2), leading to coronavirus-19 (COVID-19), was detected for the first time in Wuhan, China in December 2019. In general, governments and health authorities have taken precautions during the COVID-19 pandemic to reduce viral spread and protect vulnerable citizens. Patients with multiple myeloma (MM) have an increased risk of being infected with COVID-19 and developing a fatal course due to the MM-related immunodeficiency (Glenthøj, A et al. PMID: 32939853). To some extent, the COVID-19 pandemic has changed standard of care towards extended use of oral regimens and limiting hospital visits (Terpos E et al.PMID: 32444866). We aimed to investigate the quality of life (QoL) of Danish patients with MM during the COVID-19 pandemic. We hypothesized that patients living alone and those under the age of 65 years, as a consequence of the pandemic, would experience impaired QoL due to social isolation and fear of infection with SARS-CoV-2. Methods: The Danish prospective, nation-wide, observational survey "Quality of life in Danish patients with multiple myeloma" (QoL-MM) (Nielsen LK et al. PMID: 30656677) framed our study. In QoL-MM, survey data are obtained at enrolment and subsequently at 12 follow-up time points over a two-year period. The following PRO questionnaires are used; the cancer-generic instrument of European Organisation for Research and Treatment of Cancer Quality of life (EORTC) QLQ-C30 (EORTC QLQ-C30), the Multiple Myeloma module QLQ-MY20 (EORTC QLQ-MY20), the Chemotherapy-Induced Peripheral Neuropathy module (EORTC QLQ-CIPN20) and the Short-form health survey version 2 (SF12v2). In the present study, a subpopulation of the QoL-MM cohort was constructed, based on the response time of the questionnaires. QoL was compared using patient-reported outcome (PRO) data obtained before and during the COVID-19 pandemic at group level. In a Danish context, first wave was defined as April to June 2020 and the second wave as November 2020 to January 2021. The QoL data were analyzed using mixed effects linear regression, with a year-period-interaction. Pre-COVID versus COVID mean domain score difference was considered evident, if the difference was both statistically significant (p-value & lt;0.05) and clinically relevant, using minimal important difference (MID) defined as 0.3 standard deviation of the mean score. Results: The study included 616 patients (63% newly diagnosed and 37% relapsed) with a mean age of 68.2 years (standard deviation, 9.2); 40% were females; 76% were married/cohabiting, and 24% single. Questionnaire completion rates during the investigated periods were between 96% and 97%. In total, 1,685 completed sets of questionnaires were included in the analyses. The patients reported no statistically significant and clinically relevant difference in QoL during the first and second waves of the COVID-19 pandemic, compared to one year earlier, see table 1. When analyzing the subpopulations, we found that patients below 65 years reported improved physical health summaries (p-value 0.016), decreased fatigue (p-value & lt; 0.001), less insomnia (p-value 0.002) and improved role functioning (p-value & lt;0.001) during the first wave, reaching both statistical significance and the threshold of MID. The group of patients living alone reported improved role functioning during the first wave, reaching both statistical significance (p-value & lt;0.001) and the threshold of MID. These findings were not evident during the second wave, see table 1. Conclusion: As a group, Danish patients with MM did not report impaired QoL during the COVID-19 pandemic. In contrary, we observed improvements in some domains in patients below 65 years. Our observations indicate that the patients with MM have felt cared for and in good hands during the first and second waves of the COVID-19 pandemic. However, part of the reason for our finding of no negative impact on QoL by the pandemic could be that the questionnaires used were not developed to capture the impact of the pandemic on QoL. Importantly, our results suggest that QoL data collected in clinical trials during the pandemic allow interpretation without adjusting for the impact of the pandemic. Figure 1 Figure 1. Disclosures Redder: Janssen-Ciliag: Research Funding. Frederiksen: Alexion: Research Funding; Gilead: Research Funding; Abbvie: Research Funding; Janssen Pharmaceuticals: Research Funding; Novartis: Research Funding.
    Materialart: Online-Ressource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Society of Hematology
    Publikationsdatum: 2021
    ZDB Id: 1468538-3
    ZDB Id: 80069-7
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
    BibTip Andere fanden auch interessant ...
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