Abstract
Background: Performance status (PS) is used to estimate patients' general well-being and functional status. It is considered an important factor in clinical treatment decisions and determining eligibility for clinical trials, but there are limited data on how PS assessment by clinicians correlates with what patients are experiencing. We are conducting a prospective observational study (NCT03816683) of patients with mantle cell lymphoma (MCL) who are treated with a novel agent in 42 centers in the United States to track data on toxicities and outcomes. The study includes a patient portal used to prospectively collect information on patient-reported outcomes (PROs). The purpose of this study is to compare Eastern Cooperative Oncology Group (ECOG) PS as determined by clinicians with PROs recorded by patients.
Methods: This observational prospective cohort study is enrolling patients with MCL who have initiated any one of several predefined novel agents within the previous 3 months. The target sample size is 250 patients who will be followed for 5 years. Retrospective data from each patient's medical history and all prospective data will be collected and entered into a physician portal, including clinician-estimated ECOG PS at each time point. A separate portal will be used to concurrently collect information from patients on their disease and treatment, in addition to validated PRO questionnaires (EQ-5D-5L and EORTC QLQ-C30). Data are entered into the portals on a quarterly basis. Descriptive analyses of the PROs and ECOG PS scores at study entry were conducted by stratifying each PRO summary and/or domain score by the ECOG PS scale score. The distribution of PRO scores with continuous measures was compared between the distribution of ECOG categories using the Kruskal-Wallis test. For PROs with ordinal scales, the association of patient-reported functioning with physician assessments of functional status (ECOG PS) was analyzed using the Jonckheere-Terpstra test. The association between baseline PROs and ECOG PS was measured using Spearman correlation coefficients.
Results: Up to July 2021, we enrolled 88 patients with MCL who had ECOG PS and PRO measures recorded at baseline. Median age was 70.0 years (interquartile range [IQR]: 64.5-75.5), with 78% having past lymphoma therapy for MCL. Median number of prior therapies was 2 (IQR: 1-3). The numbers (percentages) of patients in ECOG categories 0, 1, 2, and 3 were 44/88 (50%), 35/88 (40%), 7/88 (8%), and 2/88 (2%), respectively. For EORTC QLQ-C30, we noted that physical functioning and role functioning scales were associated with ECOG PS; median physical functioning and role functioning scale scores differed between the ECOG PS categories (p=0.012 and 0.017, respectively) (Table 1). Corresponding significant inverse correlations were observed between these domains (−0.32 for physical functioning and −0.33 for role functioning). Emotional, cognitive, and social functional scales and symptom scales relating to fatigue, nausea/vomiting, pain, and dyspnea did not show this association with ECOG PS. For the EQ-5D-5L, increasing severity of problems with mobility and with usual activities was associated with worsening ECOG PS (p=0.049 and 0.001, respectively) and displayed statistically significant but weak correlations of 0.22 and 0.35, respectively. Self-care, pain/discomfort, and anxiety/depression were not associated with ECOG PS.
Conclusions: In patients with MCL enrolled in a prospective observational trial, this ad hoc interim analysis of baseline ECOG PS as determined by clinicians correlated well with physical function/mobility issues reported by patients but not with other PROs such as emotional well-being or symptoms including fatigue, pain, or dyspnea that might impact patient tolerance to treatment. These very preliminary data seem to raise the question of whether PROs might be incorporated into clinician-based assessments to better predict treatment tolerance and guide treatment selection and eligibility for trials.
Svoboda: TG: Research Funding; Seattle Genetics: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Merck: Research Funding; Incyte: Research Funding; Imbrium: Consultancy; Genmab: Consultancy; Atara: Consultancy; BMS: Consultancy, Research Funding; Astra Zeneca: Consultancy, Research Funding; Adaptive: Consultancy, Research Funding. Cohen: Janssen, Adicet, Astra Zeneca, Genentech, Aptitude Health, Cellectar, Kite/Gilead, Loxo, BeiGene, Adaptive: Consultancy; Genentech, BMS/Celgene, LAM, BioINvent, LOXO, Astra Zeneca, Novartis, M2Gen, Takeda: Research Funding. Ujjani: ACDT: Honoraria; Gilead: Honoraria; TG Therapeutics: Honoraria; Adaptive Biotechnologies: Research Funding; Atara Bio: Consultancy; Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; Kite, a Gilead Company: Honoraria; Loxo: Research Funding; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding. Andorsky: AstraZeneca: Other: served on steering committees; Celgene/Bristol Myers Squibb: Consultancy; AbbVie: Research Funding; Epizyme: Research Funding; AbbVie: Consultancy; Celgene/Bristol Myers Squibb: Research Funding. Goy: LLC(Targeted Oncology): Consultancy; Janssen: Research Funding; COTA (Cancer Outcome Tracking Analysis): Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Other: Leadership role; Bristol Meyers Squibb: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Vincerx pharma: Membership on an entity's Board of Directors or advisory committees; Genomic Testing Cooperative: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Other: Leadership role; Infinity/Verastem: Research Funding; Rosewell Park: Consultancy; Elsevier's Practice Update Oncology, Intellisphere, LLC(Targeted Oncology): Consultancy; Hoffman la Roche: Consultancy; Xcenda: Consultancy; Michael J Hennessey Associates INC: Consultancy; Janssen: Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; AbbVie/Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Acerta: Consultancy, Research Funding; Genentech/Hoffman la Roche: Research Funding; Karyopharm: Research Funding; Phamacyclics: Research Funding; Vincerx: Honoraria, Membership on an entity's Board of Directors or advisory committees; Physicians' Education Resource: Consultancy, Other: Meeting/travel support; AbbVie/Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Honoraria; Novartis: Consultancy, Honoraria; MorphoSys: Honoraria, Other; Medscape: Consultancy; Xcenda: Consultancy, Honoraria; OncLive Peer Exchange: Honoraria; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Elsevier PracticeUpdate: Oncology: Consultancy, Honoraria; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Constellation: Research Funding; Bristol Meyers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Hackensack Meridian Health, Regional Cancer Care Associates/OMI: Current Employment. Kumar: Seattle Genetics: Research Funding; Pharmacyclics: Research Funding; Abbvie Pharmaceuticals: Research Funding; Astra Zeneca: Honoraria, Other: Advisory Board, Research Funding; Kite Pharmaceuticals: Other: advisory board , Research Funding; Adaptive Biotechnologies, Celgene, Abbvie Pharmaceticals, Pharmacyclics, Seattle Genetics: Research Funding; Celgene: Honoraria, Other: advisory board, Research Funding. Ramsey: AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees. Wallington: AstraZeneca: Current Employment; Open Health: Ended employment in the past 24 months. Eudicone: Astrazeneca: Current Employment, Divested equity in a private or publicly-traded company in the past 24 months. Hermann: AstraZeneca: Current Employment, Current equity holder in publicly-traded company. Wang: Clinical Care Options: Honoraria; The First Afflicted Hospital of Zhejiang University: Honoraria; OMI: Honoraria; Mumbai Hematology Group: Honoraria; Newbridge Pharmaceuticals: Honoraria; Physicians Education Resources (PER): Honoraria; Lilly: Research Funding; Molecular Templates: Research Funding; CStone: Consultancy; Janssen: Consultancy, Honoraria, Research Funding; Anticancer Association: Honoraria; BeiGene: Consultancy, Honoraria, Research Funding; Moffit Cancer Center: Honoraria; BioInvent: Research Funding; Juno: Consultancy, Research Funding; Bayer Healthcare: Consultancy; Kite Pharma: Consultancy, Honoraria, Research Funding; Hebei Cancer Prevention Federation: Honoraria; Imedex: Honoraria; Epizyme: Consultancy, Honoraria; CAHON: Honoraria; DTRM Biopharma (Cayman) Limited: Consultancy; AstraZeneca: Consultancy, Honoraria, Research Funding; Loxo Oncology: Consultancy, Research Funding; Oncternal: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; VelosBio: Consultancy, Research Funding; Genentech: Consultancy; Dava Oncology: Honoraria; Scripps: Honoraria; Miltenyi Biomedicine GmbH: Consultancy, Honoraria; Celgene: Research Funding; BGICS: Honoraria; InnoCare: Consultancy, Research Funding; Chinese Medical Association: Honoraria; Acerta Pharma: Consultancy, Honoraria, Research Funding. Pagel: Epizyme: Consultancy; Incyte/MorphoSys: Consultancy; Pharmacyclics/AbbVie: Consultancy; MEI Pharma: Consultancy; BeiGene: Consultancy; AstraZeneca: Consultancy; Gilead: Consultancy; Actinium Pharmaceuticals: Consultancy; Kite, a Gilead Company: Consultancy.
