Primary therapy and relative survival in patients with lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia: population-based study (Netherlands, 1989-2018)
Lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia (LPL/WM) is a rare lymphoproliferative malignancy. At present, evidence from randomized clinical trials is limited to inform on optimal management of LPL/WM across various lines of therapy. Although therapeutic advances have been made, it is unclear how the changing treatment landscape has impacted the population-level survival of LPL/WM patients. Therefore, this population-based study aimed to assess trends in first-line therapy and relative survival (RS) among LPL/WM patients diagnosed in the Netherlands during a 30-year period.
All LPL/WM patients diagnosed between 1989-2018—with survival follow-up through 2020—were selected from the Netherlands Cancer Registry (NCR). Data on primary therapy—that is, no anti-neoplastic therapy (e.g. watch-and-wait) and anti-neoplastic therapy (e.g. chemotherapy)—were available in the NCR. Information on the use of rituximab and the exact anti-neoplastic therapy was available for patients diagnosed from 2007 and 2014, respectively. Patients were categorized into four periods (1989-1995, 1996-2002, 2003-2010 and 2011-2018) and three age groups (<65, 66-75, and >75 years). RS was calculated to estimate disease-specific survival.
A total of 6,461 LPL/WM patients (median age 70 years; 61% males) were included in the study. Due to broader application of an initial watch-and-wait approach, primary therapy with an anti-neoplastic agent gradually decreased over time, irrespective of age. The proportion of patients receiving first-line anti-neoplastic therapy was 59%, 62%, and 60% across the three age groups during 2011-2018. Data from 2007 onwards showed that the use of chemotherapy alone decreased over time, following increased application of chemoimmunotherapy (Figure 1A). Detailed data on primary therapy among 1,635 patients diagnosed during 2014-2018 revealed that DRC was the most frequently applied therapeutic regimen across all age groups, of which its use increased from 11% to 24% between 2014-2018. Consequently, the use of R-C(V)P decreased between 2014-2018 (Figure 1B). Five-year RS increased significantly across all age groups between 1989-1995 and 2001-2018. More specifically, 5-year RS (95% confidence intervals) was 75% (69%-79%), 65% (59%-71%), and 46% (39%-53%) in 1989-1995 across the three age groups, as compared with 93% (90%-95%), 85% (81%-89%) and 79% (73%-86%) in 2011-2018 (Figure 2). The age-stratified multivariable analysis of RS—which was simultaneously adjusted for sex and prior malignancy—demonstrated that RS between 2003-2010 and 2011-2018 did not improve.
The use of chemotherapy alone in LPL/WM seems to be almost entirely abandoned in contemporary clinical practice in the Netherlands. The impressive survival improvement over time may be accounted for by the introduction and broader application of rituximab-containing therapy since its introduction early-mid 2000. The lack of survival improvement in the post-rituximab era should bolster forthcoming studies across various lines of therapy to further improve survival in LPL/WM.