Treatment Patterns and Outcomes in a Nationwide Cohort of Older and Younger Veterans with Waldenström Macroglobulinemia, 2006-2019

Hsu-Chih Chien, Deborah Morreall, Vikas Patil, Kelli M Rasmussen, Christina Yong, Chunyang Li, Deborah G Passey, Zachary Burningham, Brian C Sauer, Ahmad S Halwani, Hsu-Chih Chien, Deborah Morreall, Vikas Patil, Kelli M Rasmussen, Christina Yong, Chunyang Li, Deborah G Passey, Zachary Burningham, Brian C Sauer, Ahmad S Halwani

Abstract

Little is known about real-world treatment patterns and outcomes in Waldenström macroglobulinemia (WM) following the recent introduction of newer treatments, especially among older adults. We describe patterns of first-line (1 L) WM treatment in early (2006-2012) and modern (2013-2019) eras and report outcomes (overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and adverse event (AE)-related discontinuation) in younger (≤70 years) and older (>70 years) populations. We followed 166 younger and 152 older WM patients who received 1 L treatment between January 2006 and April 2019 in the Veterans Health Administration. Median follow-up was 43.5 months (range: 0.6-147.2 months). Compared to the early era, older patients in the modern era achieved improved ORRs (early: 63.8%, modern: 72.3%) and 41% lower risk of death/progression (hazard ratio (HR) for PFS: 0.59, 95% CI (confidence interval): 0.36-0.95), with little change in AE-related discontinuation between eras (HR: 0.82, 95% CI: 0.4-1.7). In younger patients, the AE-related discontinuation risk increased almost fourfold (HR: 3.9, 95% CI: 1.1-14), whereas treatment effects did not change between eras (HR for OS: 1.4, 95% CI: 0.66-2.8; HR for PFS: 1.1, 95% CI: 0.67-1.7). Marked improvements in survival among older adults accompanied a profound shift in 1 L treatment patterns for WM.

Keywords: Waldenström macroglobulinemia; age groups; older adults; rare cancer; real-world evidence; treatment outcomes; treatment patterns.

Conflict of interest statement

A.H. has received research grant support from Bristol Myers Squibb, Kyowa Hakko Kirin, Seattle Genetics, Roche, Genentech, Miragen, Immunedesign, Takeda, Amgen, Pharmacyclics, and AbbVie. B.C.S. has received research grant support from Roche, Genentech, Pharmacyclics, and AbbVie. H.-C.C., D.M., V.P., K.M.R., C.Y., C.L., D.G.P. and Z.B. certify that they have no conflicts of interest to declare. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure A1
Figure A1
Number of patients receiving active first-line treatments for Waldenström macroglobulinemia per quarter-year, 2006 to 2019: (a) number of patients on active first-line treatments in younger population (70 years of age or younger at initiation of 1 L therapy); (b) number of patients on active first-line treatments in older population (older than 70 years of age at initiation of 1 L therapy).
Figure A2
Figure A2
Hazard ratios of overall survival, progression-free survival and discontinuation due to adverse events in patients receiving first-line treatments for Waldenström macroglobulinemia in early (2006 to 2012) and modern eras of younger (70 years of age or younger at initiation of 1 L therapy) and older (older than 70 years of age at initiation of 1 L therapy) populations, in primary and sensitivity analysis settings. AE: adverse event; CI: confidence interval; HR: hazard ratio; PFS: progression free survival; PFS2: progression free survival counting all deaths after lost of follow up as events for PFS (the second setting for sensitivity analyses); OS: overall survival; TTP: time to progression (the first setting of sensitivity analyses).
Figure 1
Figure 1
Cohort selection flowchart.
Figure 2
Figure 2
1 L treatment patterns in veterans with Waldenström macroglobulinemia, 2006–2019: (a) 1 L treatment pattern in younger patients (≤70 years of age at initiation of 1 L therapy); (b) 1 L treatment pattern in older patients (>70 years of age at initiation of 1 L therapy).1 L: first-line treatment; BDR: bortezomib and dexamethasone +/− rituximab; BR: bendamustine +/− rituximab; Chloram: chlorambucil; DRC: dexamethasone, rituximab, and cyclophosphamide; FCR: fludarabine and cyclophosphamide +/− rituximab; R: rituximab; RCHOP: cyclophosphamide, doxorubicin, vincristine, and prednisone ± rituximab.
Figure 3
Figure 3
Treatment utilization trends in BDR, BR, ibrutinib, DCR, and single-agent rituximab, 2006–2019. BDR: bortezomib and dexamethasone +/− rituximab; BR: bendamustine +/− rituximab; DRC: dexamethasone, rituximab, and cyclophosphamide; R: rituximab.
Figure 4
Figure 4
Progression-free survival, overall survival, and adverse event-related discontinuation in veterans with Waldenström macroglobulinemia, 2006 to 2019. 1 L: first-line treatment; AE: adverse event; Early: early era, 2006–2012; Modern: modern era, 2013–2019; OS: overall survival; PFS: progression-free survival.

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