denotes an abstract that is clinically relevant.
denotes that this is a recommended PHD Trainee Session.
denotes that this is a ticketed session.Session: 653. Multiple Myeloma: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Combination therapy, Adult, Diseases, Treatment Considerations, Myeloid Malignancies, Study Population, Human
Methods. The European Organization for Research and Treatment of Cancer core questionnaire (EORTC QLQ-C30) and the multiple myeloma module (MY20) were administered on day 1 of every treatment cycle (C), at the end of treatment (EOT), and at one follow-up visit after EOT. Longitudinal analyses of change from baseline (BL) using mixed models for repeated measures were conducted through C63, with a threshold of 5 points for interpreting differences between treatment arms. Time to first deterioration (TTFD) and time to confirmed deterioration (TTCD) were assessed using Kaplan-Meier estimates and Cox models. All analyses were prespecified and conducted in the intent-to-treat (ITT) population. No adjustment for multiplicity was made and all reported p-values are nominal.
Results. A total of 446 patients were randomized 3:2 to Isa-VRd (n=265) or VRd (n=181). Completion rates were >90% at BL and remained high during treatment (approximately 70% at EOT) in both arms. At BL, patient reported functioning and symptom burden were similar in both arms. During a median follow-up of ~5 years (59.73 months [mo]), improvement from BL was observed in the Isa-VRd arm in most HRQoL symptom scales and functional domains. The overall positive impact of Isa-VRd on HRQoL was reflected in global health status/QoL (GHS/QoL) scores. GHS/QoL improved until C19 and then remained stable in both treatment arms at all time points thereafter (overall LS mean change [95% CI]: 3.45 [1.51, 5.40] in Isa-VRd, 2.41 [0.24, 4.59] in VRd; p=0.3587). Additionally, patients receiving Isa-VRd reported clinically meaningful better physical functioning vs. VRd (overall LS mean difference [95% CI]: 5.92 [2.76, 9.08]; p=0.0003). The median TTFD in physical functioning trended to be longer in the Isa-VRd arm vs. VRd (median TTFD [95% CI]: 5.78 [4.27, 7.43] mo in Isa-VRd, 4.27 [3.06, 5.75] mo in VRd; p=0.0720) with a similar trend observed for TTCD (median TTCD [95% CI]: 34.23 [26.55, 54.14] mo in Isa-VRd, 22.47 [11.24, 59.60] mo in VRd; p=0.1599). Cognitive functioning declined over time in both arms (p>0.05).
Improvements in certain disease-related symptoms such as pain and dyspnea were also observed in the Isa-VRd arm. Despite relatively low pain levels at BL, patients in both arms reported reduction in pain as early as C2 which was sustained throughout the study. Pain reduction showed a trend towards being numerically greater with Isa-VRd vs. VRd (overall LS mean difference: ‑2.78, 95% CI [-6.36, 0.80]; p=0.1281). Isa-VRd significantly delayed TTFD in the pain subscale (median TTFD [95% CI]: 6.51 [4.76, 8.41] mo in Isa-VRd vs. 4.24 [2.92, 5.59] mo in VRd; HR [95% CI]: 0.75 [0.59, 0.94]; p=0.0146). Median TTCD in pain was also numerically longer in the Isa-VRd arm (p>0.05). Notably greater improvement in dyspnea was reported by patients in the Isa-VRd arm vs. those in VRd arm (overall LS mean difference: -3.20, 95% CI [-6.33, -0.08]; p=0.0447). Moreover, Isa-VRd delayed TTFD and TTCD in dyspnea vs VRd (p<0.05).
While patients in both arms reported a modest worsening in side effects of treatment as measured by MY20, the magnitude of change was numerically lower with Isa-VRd suggesting no additional toxicity with the addition of Isa to VRd (overall LS mean change [95% CI]: 2.75 [0.90, 4.59] in Isa-VRd, 4.76 [2.71, 6.81] in VRd; p=0.0680). Median TTCD in side effects of treatment was longer in Isa-VRd arm (p>0.05).
Conclusions. Isa-VRd was associated with faster and durable improvement in HRQoL vs. VRd, including physical functioning, pain, and dyspnea, throughout a follow-up period of ~5 years. The improved efficacy reported previously for Isa-VRd, together with this evidence of maintained or improved HRQoL supports the overall benefit of Isa-VRd for patients with NDMM who are ineligible for transplantation.
Disclosures: Dimopoulos: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; Menarini: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; Swixx: 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, Other: Consulting fee; BeiGene Inc: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consulting fee; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen, Abbvie, Takeda, Beigene, BMS, GSK, Janssen, Menarini, Regeneron, Sanofi: Other: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events. Beksac: BMS, Takeda, Janssen, Menarini, Amgen, GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS, Janssen, Takeda, Sanofi: Speakers Bureau. Hajek: Takeda: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy; BMS: Consultancy, Honoraria, Research Funding; PharmaMar: Consultancy, Honoraria; Novartis: Consultancy, Research Funding. Minarik: Amgen: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: 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; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Moreau: Celgene, Janssen, Takeda, Amgen, Pfizer, AbbVie, Sanofi: Consultancy; Celgene, Janssen, Takeda, Amgen, Pfizer, AbbVie, Sanofi: Honoraria; Celgene, Janssen, Takeda, Amgen, Pfizer, AbbVie, Sanofi: Other: Participation on a Data Safety Monitoring Board or advisory board . Romejko-Jarosinska: AstraZeneca, Gilead, Roche, Janssen, Celgene, Sanofi, Takeda: Honoraria, Speakers Bureau; Gilead, Roche, Takeda: Other: Support for attending meetings and/or travel; Swixx: Other: Participation on a Data Safety Monitoring Board or advisory board. Špička: Charles University and General University Hospital in Prague, Czech republic: Current Employment; BMS: Honoraria; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria; Johnson and Johnson: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Besemer: Takeda: Honoraria; Janssen: Honoraria; Oncopeptides: Honoraria; AMGEN: Honoraria; Pfizer: Honoraria; GlaxoSmithKline: Honoraria. Parmar: Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grant; Janssen Biotech: Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Other: travel grants. Zamagni: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Menarini Stemline: 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; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees. Goldschmidt: Chugai: Honoraria, Other: Grants and/or provision of Investigational Medicinal Product; Celgene: Research Funding; GlaxoSmithKline (GSK): Honoraria, Other: Support for attending meetings and/or travel, Research Funding; GlycoMimetics Inc.: Research Funding; Heidelberg Pharma: Research Funding; Hoffmann-La Roche: Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product; support for attending meetings and/or travel, Research Funding; Incyte Corporation: Research Funding; Karyopharm: Research Funding; Merck Sharp and Dohme (MSD): Research Funding; Millennium Pharmaceuticals Inc.: Research Funding; Molecular Partners: Research Funding; MorphoSys AG: Research Funding; Novartis: Honoraria, Other: Support for attending meetings and/or travel, Research Funding; Pfizer: Honoraria, Other: Support for attending meetings and/or travel, Research Funding; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants and/or provision of Investigational Medicinal Product; support for attending meetings and/or travel, Research Funding; Takeda: Research Funding; Array Biopharma/Pfizer: Other: Grants and/or provision of Investigational Medicinal Product; Bristol Myers Squibb/Celgene: Other: Grants and/or provision of Investigational Medicinal Product; Dietmar Hopp Foundation: Other: Grants and/or provision of Investigational Medicinal Product; Johns Hopkins University: Other: Grants and/or provision of Investigational Medicinal Product; Adaptive Biotechnologies: 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, Other: Support for attending meetings and/or travel, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel; grants and/or provision of Investigational Medicinal Product, Research Funding; Mundipharma GmbH: Other: Grants and/or provision of Investigational Medicinal Product. Martin: Pfizer: Honoraria; Roche: Honoraria; GSK: Honoraria; BMS: Research Funding; Sanofi: Research Funding; Janssen: Research Funding; AMGEN: Research Funding. Manier: Abbvie: Consultancy; Adaptive Biotechnology: Consultancy; Amgen: Consultancy; Celgene/BMS: Consultancy; GlaxoSmithKline: Consultancy; Janssen: Consultancy; Novartis: Consultancy; Regeneron: Consultancy; Roche: Consultancy; Sanofi: Consultancy; Takeda: Consultancy. Mohty: Novartis: Honoraria; Takeda: Honoraria; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Honoraria; Pfizer: Consultancy, Current holder of stock options in a privately-held company, Honoraria, Research Funding, Speakers Bureau; GSK: Honoraria; Jazz: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria; Adaptive: Honoraria; Stemline Menarini: Honoraria; MaaT Pharma: Current equity holder in publicly-traded company. Orlowski: Bristol Myers Squibb, CARsgen Therapeutics, Exelixis Inc, Heidelberg Pharma, Janssen Biotech Inc, Sanofi, Takeda Pharmaceuticals USA Inc; Laboratory Research Funding: Asylia Therapeutics Inc, BioTheryX Inc, Heidelberg Pharma: Research Funding; AbbVie Inc, Adaptive Biotechnologies Corporation, Asylia Therapeutics Inc, BioTheryX Inc, Bristol Myers Squibb, Karyopharm Therapeutics, Meridian Therapeutics, Monte Rosa Therapeutics, Nanjing IASO Biotherapeutics, Neoleukin Therapeutics, Oncopeptides, Pf: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; DEM BioPharma, Inc., Karyopharm Therapeutics, Lytica Therapeutics, Meridian Therapeutics, Monte Rosa Therapeutics, Myeloma 360, Nanjing IASO Biotherapeutics, Neoleukin Corporation, Oncopeptides AB, Pfizer, Inc., Regeneron Pharmaceuticals, Inc., Sporos Bio: Membership on an entity's Board of Directors or advisory committees; BioTheryX: Membership on an entity's Board of Directors or advisory committees, Research Funding; Asylia Therapeutics Inc.: Current equity holder in private company, Patents & Royalties; Sanofi, Takeda Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding. Comerford: Sanofi: Other: Employee of Sanofi and may hold stock/stock options in Sanofi.. Msihid: Sanofi: Other: Employee of Sanofi and may hold stock/stock options in Sanofi.. Lin: Sanofi: Current Employment, Other: Employee of Sanofi and may hold stock/stock options in Sanofi.. Leleu: GSK, Novartis, BMS, Takeda Pharmaceuticals, Abbvie: Honoraria, Other: Consulting Fee, Speakers Bureau; Janssen, Sanofi, Pfizer: Honoraria, Other: Consulting fee, support for attending meetings and travel, Speakers Bureau.
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