Real World Treatment Outcomes in the First Line Management of Waldenström Macroglobulinemia from the Global Patient Derived Data Registry, Whimsical
Authors: Low Ryan , Warden Andrew , Postek Michelle , Denardis Peter , Kyriakou Charalampia , Olszewski Adam J. , Kersten Marie José , Vos Josephine M.I. , Thomas Sheeba K. , D'Sa Shirley , Guerin Newton , Harrington Carl , Trotman Judith , Tohidi-Esfahani Ibrahim 
Published: December 2024

Introduction: WhiMSICAL (Waldenström Macroglobulinemia Study Involving CArt-wheeL) is a global Waldenström Macroglobulinemia (WM) patient-derived data registry that aims to address important research questions in treatment of WM, linked with longitudinal quality of life (QoL) data. Bendamustine and Rituximab (BR) is often the standard first-line treatment for WM, while Bruton Tyrosine-Kinase inhibitors (BTKi) have emerged as an alternative option. With prolonged progression free survival (PFS) with both treatment options for this rare lymphoma, there is unlikely to be a randomised trial comparing these regimens. This study aimed to assess treatment outcomes and QoL data for BR compared to BTKi in the first-line setting.
Method: WhiMSICAL captures patient-entered data regarding treatment and QoL information (EORTC-QLQ-C30), after patients register and provide informed consent for the online rare cancer database, www.cart-wheel.org. Recruitment to the registry is driven by patient and advocate investigators in the International Waldenström Macroglobulinemia Foundation, with frequent messaging through social media to encourage updating of data entry. We analysed data entered up until 26th July 2024. The time to next treatment (TTNT) was assessed from start of first-line therapy to start of next therapy. Patients without a documented next therapy were censored at the time of last edit to their data. Follow-up duration was determined as being from start of first-line treatment to the date of the patient's last edit. The TTNT was compared between first-line BR and BTKi. The first QoL scores entered post initiation of treatment were compared between both first-line treatments (QoL score were limited to within 12 months of commencing first line BR vs QoL score on BTKi).
Results: As of the data cut off, a total of 704 patients from 23 countries had entered data into the registry, with median follow-up since diagnosis of 79 months (interquartile range 42-135). The majority of patients were from the USA (64%) and Australia (26%). There was a male predominance (63%), with a median age at diagnosis of 59 years. 501 (71%) patients underwent a first-line treatment. The most common first line therapy was BR (n=133); this group was compared with patients entering BTKi as first line therapy (n=63). There was no significant difference between the two treatment groups in terms of median age (BR 62 years, BTKi 65 years, p=0.18). With a median follow up of 45 months, the TTNT was not significantly different between first line BR versus BTKi, with median not reached vs 8.9 years, respectively (p=0.31). The impact of the therapies on QoL were assessed at a median of 5 months post BR and 16 months post commencement of BTKi. Patients on BTKi reported significantly better EORTC QLQ-C30 global scale scores: mean 80.3 ± 16.4, BR-treated patients mean 68.2 ± 19.0 (p=0.0014).
Conclusion: Patient derived data from the global WhiMSICAL registry continues to accumulate. The registry provides further support that BR remains an excellent first-line treatment option for patients with WM with comparable long-term outcomes to BTKi. There is a suggestion that the impact on QoL is superior in patients on a BTKi, however further longitudinal QoL analyses will be conducted for more in-depth comparison between BR and other time limited therapies and continuous BTKi.