<scp>WhiMSICAL</scp> : A global Waldenström's Macroglobulinemia patient?derived data registry capturing treatment and quality of life outcomes

To the Editor: Waldenström's Macroglobulinemia (WM) is a low-grade non-Hodgkin lymphoma with an incidence of approximately three per million-persons year,1 classifying it as rare cancer. Rare cancers are inherently difficult to study in large clinical trials, resulting paucity well-founded evidence. As such, diverse manifestations disease and response different treatments, including quality life (QoL) outcomes, less well-understood than more common cancers. Patient-derived data can facilitate generation datasets help address this gap. A small number treatment regimens for WM identified options first subsequent lines therapy international guidelines,2 however, real-world practices vary significantly.3 This disconnect between guidelines availability practice likely contributes global disparity cancer survival.4 Illuminating nature through databases will assist identifying areas which focus resource allocation. enhance understanding practices, well provide complementary view how treatments accessed, their impact on QoL other patient-reported outcomes (PROs). systematic review randomized controlled trials PROs independently prognostic overall survival,5 thus, improved capture care research essential. Here, we present WhiMSICAL (Waldenström's Study Involving CART-WHEEL), database capturing patient-derived demographic, PRO data, insights gained from contributions 453 patients. Developed by clinicians International Foundation (IWMF) patient-investigators, aims patient priorities map guide patients clinicians. Recruitment began June 2016, patient-initiated registration at www.cart-wheel.org, (Centre Analysis Tumors), online hosted secure BioGrid Australia platform, utilizing comprehensive questionnaire. The www.cart-wheel.org was approved Melbourne Health Human Research Ethics Committee (HREC 2007.260). amendment questionnaire additional points Sydney Local District – Concord Repatriation General Hospital (LNR/16/CRGH/30). Patients complete consent form following multiple levels (see supplement). total were recruited analysis cut-off, July 2020, driven social media messaging IWMF members globally. Data completion rates variable, over 80% entering diagnosis, symptoms, PROs, reducing 50% pathology results. Patient characteristics outlined Table S1. population included participants 19 countries, predominantly USA (46%) (26%). majority male (61%), median age 70 (range 27–88) years follow-up 68 months (IQR 34–117). compared Rest-of-World (ROW) marginally older, but otherwise no significant differences observed. Participants entered disease-related providing date symptom onset end, results matched documented diagnosis. Fatigue/muscle weakness (46%), B-symptoms (21%) peripheral neuropathy (19%) symptoms most frequently reported, 30% asymptomatic Interestingly, 10% reported leg cramps While close half anemic (Hb < 11.5 g/dL) few had cytopenias. 302 who received 46 unique first-line therapies after combining all trial (Figure 1(A)). variation maintained across although higher 36 used (n = 136) 27 ROW 166). remained when considering initiated since 2016 (time release last guidelines2), 125). Bendamustine rituximab (BR) therapy, 74/302 (25%) overall, 55/125 (44%) treated 2016. Evaluation demonstrated that commenced significantly earlier, time diagnosis being 48 days 15–265, n 116) 100 17–755, 131, p .04, Figure 1(B)), despite proportion smoldering (USA 19%, 13.7%). When comparing only those active 34 days, whereas 56 (p .04). treatment, hemoglobin 9.8 g/dL 8.6–11.0, 72) patients; 11 9.5–12.4, 57, .006, 1(C)). IgM not .60). 29% government-funded 5% provided ROW, 57% 13%, respectively .001 .001, respectively). Employer-purchased insurance main source funding (43% S2). evaluate next (TTNT) assessed four therapies. unmatched populations encouraging TTNT BR cohort 1(D)). Patient-reported measured using two tools: Impact Event Scale-6 (IES-6),6 measure current post-traumatic stress related EORTC QLQ-C30 Based IES-6 scores (ranging 0 24 maximal stress), 43 15–98) post-diagnosis, ?13, consistent disorder (94% positive predictive value, S1A). However, improvement score entries (separated 20 months, IQR 13–35, 157, S1B). Using scale snapshot analysis, taking BTKi scores, mean 80.1 ± 16.2 44), exposed been within 12 months: 68.3 22.6 .004, S1C). having undergone prior 1–4) non-BTKi (median 1, 1–2, .001). These findings represent largest malignancy. Note, registry information, helping bridge gap lymphoid malignancy entities. Furthermore, agile, able rapidly questions, such currently evaluating Covid-19 questions implemented 14 days. has feasible partnership community, involved sources entry, key investigators. Thus, marked persisting released 2016.2 highlights fact while exist, there may be lack familiarity with, or access to, recommended earlier counterparts, becoming before initiated. reflect geographical disparities certain So, offers platform deeper adoption financial toxicity Also, generates outcome TTNT. lacks matching baseline characteristics, many cohorts grow longer follow-up. With ongoing parallel potential continually aiding clinician decision making. Direct reporting allowed greater experiences PROs. New include high have disorder. We demonstrate burden, better never months. further entry time, these confirmed longitudinal analyses. There are, course, several limitations kind, gaps survivor bias. uptake increases anticipated become prospective comprehensive, overcoming limitations. In conclusion, demonstrates feasibility agility ethically-approved direct patients, WM-related responses diversity correlates QoL. Such rarely available routine increasingly important era novel authors would like thank acknowledge contributing strong recruitment geographic regions reflects support individual IWMF-affiliates globally, particular acknowledgements Ron Ternoway Arlene Hinchcliffe Canada (WMFC), Lea Hullett Zealand (WM-NZ), Neil Motyer WMozzies Australia, Hans Scheurer, President Myeloma Europe previously board member Hematon, Netherlands Lindsey Bennister, chief executive WMUK. also express gratitude generous Bloody Great Cause, Concord, NSW 2139 Australia. Ibrahim Tohidi-Esfahani, Andrew Warden, Elena Malunis, Peter L. DeNardis, Javier Haurat, Marita Black, Damien Kee, Carl Harrington, Clare Scott, Judith Trotman responsible design. Tohidi-Esfahani primarily draft writing manuscript finalization. All authors, Stephen Opat, Shirley D'Sa, Ruth Spearing, Marie-José Kersten, Maria Lia Palomba, Adam J. Olszewski, contributed collection, interpretation, carefully reviewed final version. I.T J.T indirect (to Australia) initial WM-specific Janssen-Cilag. JT reports institutional Pharmacyclics, Beigene, Roche, BMS, Takeda, Janssen-Cilag Celgene. A.W personal fees (event photoshoot) Janssen-Cilag, outside submitted work. S.O consultancy, honoraria, membership advisory AbbVie, Merck, AstraZeneca; BeiGene Gilead; CSL Behring; Epizyme, S.D honoraria Janssen-Cilag; Sanofi, M.K (travel grant board) Roche (including presentation), MSD, Janssen/Cilag, Amgen, Novartis Kite/Gilead Celgene Miltenyi Biotech; grants institution Takeda M.L.P speaker A.J.O Genentech/Roche, TG Therapeutics, Spectrum Pharmaceuticals Adaptive Biotechnologies, C.H stock ownership BeiGene, Bristol-Myers Squibb, Gilead, Idera Calithera Biosciences, C.L.S Director umbrella organization hosting CART-WHEEL.org. E.M, P.L.D, J.H, M.B, R.L.S declare competing interests. third party fund amendment. They role designing any aspect design; writing, regarding submission publication. Original, de-identified shared upon approval Committee, Committee. publicly due privacy ethical restrictions. For original please contact corresponding author emailing [email protected]. Appendix S1: Supporting information Please note: publisher content functionality supporting supplied authors. Any queries (other missing content) should directed article.