Whimsical (Waldenström's Macroglobulinemia Study Involving CArt-wheeL): Empowering Patients Internationally to Contribute Patient-Derived Data for Observational Research

Introduction

Waldenström's Macroglobulinemia (WM), a rare cancer with easily trackable disease parameters, is difficult to study in large trials. Patient-derived data are an attractive option to increase breadth of knowledge. The value of patient reported outcomes (PROs) is increasingly evident, with integration of electronic reporting of symptoms in cancer care shown to improve health outcomes and survival (Baasch, 2017).

WM patients are well connected through the International Waldenström's Macroglobulinemia Foundation (IWMF) and its affiliates, using internet and social media. As a patient group, they are relatively well informed about their disease, its parameters (IgM, hemoglobin) and available treatments.

This study utilised www.cart-wheel.org, an ethically-approved online rare cancer database for patient-derived data, and the digital connectedness of WM patients to develop a continuously expanding patient-derived dataset, providing foundation for hypothesis generation around WM PROs and improving our understanding of this rare disease.

Methods

An ethics committee-approved WM-specific extension to www.cart-wheel.org's questionnaire, developed by clinician and patient investigators, went online June 2016. Participants complete an online consent form and provide data on symptoms, pathology results, treatments, their tolerance and how they were accessed. Following development of online consent and demonstration of feasibility with Australian recruitment, international promotion by the IWMF was undertaken through utilisation of multiple social media platforms, including online discussion forums, Facebook, email mailing lists and community newsletters. Patients are encouraged to print out their personal www.cart-wheel.org report and review any missing data with their clinician. Data analysis will be conducted utilising independent samples t-test, cross-tabulation and Pearson Chi-squared.

Results

The local recruitment drive demonstrated initial project feasibility with 69 participants. Following international promotion in May 2017, 137 further participants were recruited in 10 weeks. The 206 participants were predominantly from USA (45%), Australia and New Zealand (30%), Canada (10%), UK (7%) and Netherlands (4%), with median age 67 years (43-85) and male predominance (62%). Median age at diagnosis was 60 (41-83) with 22 (11%) diagnosed under 50 years of age. Of the 123 (60%) patients who provided symptom data at diagnosis, fatigue was most common (56%), correlating with median hemoglobin 11.1 g/dL (5.2-12.9 g/dL, n=39) compared to 12.4 g/dL (4.4-15.4 g/dL, n=44) in those without fatigue (p=0.005), and trend to higher IgM (median IgM 3410 mg/dL, non-fatigued 2875 mg/dL, p=0.33). Other common symptoms were B-symptoms (entered as weight loss >10%, fever or night sweats, 28%), peripheral neuropathy (documented specifically or as numbness/tingling, 28%), leg cramps (15%) and epistaxis (nose bleeding, 14%). Median IgM at diagnosis was 3190 mg/dL (30-10300 mg/dL, n=79) and hemoglobin 11.6 g/dL (4.4-16.6 g/dL, n=86), whereas at first treatment, medians were 3814 mg/dL (50-6800 mg/dL, n=58) and 10.2 g/dL (4.4-15.4 g/dL, n=64), respectively (p=0.27 and p=0.003, respectively). Thirty-two different first-line therapeutic combinations were documented by 125 participants. From diagnosis, median time to first treatment was 82 days (0-8803 days, n=119), with median time for USA patients being 59.5 days (0-8803, n=54) and Rest of World (ROW) patients 106 days (0-5765, n=66), (p=0.23). Treatment access data was available for 121 (91%) of 133 therapies provided by USA patients, with 32 (26%) therapies government funded, whereas in ROW patients, access data was available for 120 (85%) of 141 therapies, 69 (58%) being government funded.

Conclusion

This study demonstrates a robust data-collection platform via www.cart-wheel.org and the feasibility of its use globally for WM patient-derived data. Upon further recruitment and encouragement of more complete and continuous data entry, an expanding and increasingly robust body of data will increase knowledge of the range of presentations and treatment experiences of WM patients. Future graduated database additions will include validated PROs (e.g. EuroQol EQ-5D-5L). WhiMSICAL has the potential to map real-world therapeutic efficacy, along with international patterns of treatment access.