Association of patient activity bio-profiles with health-related quality of life in patients with newly diagnosed multiple myeloma: a prospective observational cohort study.

Background: Due to the nature of their disease, patients with multiple myeloma (MM) often have bone disease-related pain that limits physical activity and diminishes health-related quality of life (HRQOL). Digital health technology with wearables and electronic patient reported outcome (ePRO) tools can provide insights into MM HRQoL. Methods: In this prospective observational cohort study conducted at Memorial Sloan Kettering Cancer in NY, NY, USA, patients with newly diagnosed MM (n = 40) in two cohorts (Cohort A - patients <65 years; Cohort B - patients ≥65 years) were passively remote-monitored for physical activity at baseline and continuously for up to 6 cycles of induction therapy from Feb 20, 2017 to Sep 10, 2019. The primary endpoint of the study was to determine feasibility of continuous data capture, defined as 13 or more patients of each 20-patient cohort compliant with capturing data for ≥16 h of a 24-hr period in ≥60% of days of ≥4 induction cycles. Secondary aims explored activity trends with treatment and association to ePRO outcomes. Patients completed ePRO surveys (EORTC - QLQC30 and MY20) at baseline and after each cycle. Associations between physical activity measurements, QLQC30 and MY20 scores, and time from the start of treatment were estimated using a linear mixed model with a random intercept. Findings: Forty patients were enrolled onto study, and activity bioprofiles were compiled among 24/40 (60%) wearable user participants (wearing the device for at least one cycle). In an intention to treat feasibility analysis, 21/40 (53%) patients [12/20 (60%) Cohort A; 9/20 (45%) Cohort B] had continuous data capture. Among data captured, overall activity trended upward cycle over cycle for the entire study cohort (+179 steps/24 h per cycle; p = 0.0014, 95% CI: 68-289). Older patients (age ≥65 years) had higher increases in activity (+260 steps/24 h per cycle; p < 0.0001, 95% CI: -154 to 366) compared to younger patients (+116 steps/24 h per cycle; p = 0.21, 95% CI: -60 to 293). Activity trends associated with improvement of ePRO domains, including physical functioning scores (p < 0.0001), global health scores (p = 0.02), and declining disease burden symptom scores (p = 0.042). Interpretation: Our study demonstrates that feasibility of passive wearable monitoring is challenging in a newly diagnosed MM patient population due to patient use. However, overall continuous data capture monitoring remains high among willing user participants. As therapy is initiated, we show improving activity trends, mainly in older patients, and that activity bioprofiles correlate with traditional HRQOL measurements. Funding: Grants -National Institutes of HealthP30 CA 008748, Awards - Kroll Award 2019.

Examining health related quality of life outcomes in multiple myeloma: Past and future perspectives.

Multiple myeloma (MM) is a complex hematological malignancy. Advances in therapy over the last decade have resulted in significant improvement in overall survival for patients with a diagnosis of MM, leading to a substantial number of older people living with the disease. However, patients continue to suffer from a multitude of debilitating symptoms that can significantly affect their quality of life, a problem that especially can impact patients with MM considered in the geriatric age group. In the first part of our review, we reflect on traditional measurement tools that are used to assess health related quality of life in patients living with MM, as they undergo different types of treatment regimens. In the second part, we discuss the potential role of the Internet of Medical Things in tracking and actively enhancing health related quality of life in patients with a diagnosis of MM. We conceptualize models of passive and active digital health technology platforms that are posed to transform the patient-physician relationship in the new era of advanced care.

Of mice and men: a novel dietary supplement for the treatment of ulcerative colitis.

BACKGROUND: Curcumin, green tea polyphenols and selenium possess anti-inflammatory and anti-oxidant properties. Individually they have demonstrated some efficacy in animal models and human subjects with inflammatory bowel disease (IBD). To evaluate the efficacy and safety of Coltect [Curcumin (500 mg), green tea (250 mg) and selenium (100 µg)] in vivo and in patients with ulcerative colitis (UC). METHODS: Each component was compared to placebo in a DSS mice colitis model. The efficacy was validated in a 2,4,6-trinitrobenzenesulfonic acid (TNBS) rat colitis model. Twenty patients with mild-to-moderate UC received two Coltect tablets twice daily for 8 weeks. Enrollees underwent sigmoidoscopy at study entrance and closure, and physical and laboratory evaluation at baseline, 4 and 8 weeks. RESULTS: Coltect showed a synergistic therapeutic effect in the DSS and TNBS models. Disease activity was significantly higher in the placebo versus the treated group (p < 0.05). Selenium was the more active component. The contribution of green tea was minor. In the TNBS model, the Wallace scores for macroscopic lesions were 4.8 ± 1.5 (treatment) and 8.2 ± 0.5 (placebo) (p = 0.01). In humans, Coltect was well tolerated and effective. Fourteen subjects (70%) improved: nine (45%) went into complete remission, four (20%) experienced marked improvement and one (5%) experienced moderate improvement at the end of the trial. Clinical activity index decreased significantly at 4 and 8 weeks (p < 0.001). Two patients had no change in their symptoms, and one withdrew after 4 weeks. Flare-up in four subjects caused three to withdraw from the study after less than 4 weeks. Endoscopic improvement was observed in 11 (69%) patients, and four patients (25%) achieved complete remission. CONCLUSIONS: Coltect may serve as a first-line or add-on therapy in patients with mild-to-moderate UC.

Selective eradication of cancer cells by delivery of adenovirus-based toxins.

BACKGROUND AND OBJECTIVE: KRAS mutation is an early event in colorectal cancer carcinogenesis. We previously reported that a recombinant adenovirus, carrying a pro-apoptotic gene (PUMA) under the regulation of Ets/AP1 (RAS-responsive elements) suppressed the growth of cancer cells harboring hyperactive KRAS. We propose to exploit the hyperactive RAS pathway, rather than to inhibit it as was previously tried and failed repeatedly. We aim to improve efficacy by substituting PUMA with a more potent toxin, the bacterial MazF-MazE toxin-antitoxin system, under a very tight regulation. RESULTS: A massive cell death, in a dose-dependent manner, reaching 73% at MOI 10 was seen in KRAS cells as compared to 22% in WT cells. Increase expression of MazE (the anti-toxin) protected normal cells from any possible internal or external leakage of the system and confirmed the selectivity, specificity and safety of the targeting system. Considerable tumor shrinkage (61%) was demonstrated in vivo following MazEF-encoding adenovirus treatment without any side effects. DESIGN: Efficient vectors for cancer-directed gene delivery were constructed; "pAdEasy-Py4-SV40mP-mCherry-MazF""pAdEasy-Py4-SV40mP-mCherry-MazF-IRES-TetR-CMVmp-MazE-IRES-EGFP","pAdEasy-ΔPy4-SV40mP-mCherry-MazF-IRES-TetR-CMVmp-MazE-IRES-EGFP "and "pAdEasy-mCherry". Virus particles were produced and their potency was tested. Cell death was measured qualitatively by using the fluorescent microscopy and colony formation assay, and was quantified by MTT. FACS analysis using annexin V and RedDot2 dyes was performed for measuring apoptotic and dead cells, respectively. In vivo tumor formation was measured in a xenograft model. CONCLUSIONS: A proof of concept for a novel cancer safe and effective gene therapy exploiting an aberrant hyperactive pathway is achievable.