Rituximab confers a significant survival benefit when used as part of first-line treatment for WM/LPL

On 5th July in the British Journal of Haematology, Adam J. Olszewski from Brown University Warren Alpert Medical School and Rhode Island Hospital, Providence, RI, USA, et al. published an observational, population-based study of older patients (≥65 years) with Waldenström Macroglobulinemia (WM) or Lymphoplasmacytic Lymphoma (LPL) and who began first-line treatment between 1999–2013.

Data from the linked SEER-Medicare database, which contains records from 18 US cancer registries, was used and analyzed for Overall Survival (OS), risk of hospitalizations, transfusions, and plasmapheresis. A propensity score-based causal inference method was used to reduce bias. In total, three analyses were conducted: patients treated with or without rituximab (cohort A), patients treated with rituximab monotherapy or with combination immunochemotherapy, and regimens based on classic purine analogues or alkylators.

Key Highlights:
  • Overall, 1,310 pts were eligible for the analysis; median age = 78 years (range, 65–98)
  • Number of pts who received: rituximab monotherapy = 711 (54.3%); rituximab + purine analogue = 153 (11.7%); rituximab + alkylator = 164 (12.5%); purine analogue alone = 178 (13.6%); alkylator alone = 104 (7.9%)
  • Median time from diagnosis to treatment = 2 months (range, 0–166); 75.3% of pts began treatment ≤1 year from diagnosis
  • Pts who received rituximab/chemo combinations had a shorter median time to treatment of 1 month (range, 0–126)
  • Median follow-up = 5 years
  • Unadjusted 5-year OS = 49.1% (95% CI, 46.2–52.0); median OS = 4.9 years (95% CI, 4.4–5.3)
  • 5-year OS in pts treated: without rituximab = 42.0%; with rituximab monotherapy = 50.6%; with combination immunochemotherapy = 51.9%
  • Cohort A (n = 1,310)
    • In pts who received rituximab, OS was significantly improved compared to pts who did not (paired HR, 0.62; 95% CI, 0.55–0.71)
    • Significantly lower rate of transfusions (risk difference, -3.3%; 95% CI, -6.3 to -0.3) found in pts who received rituximab
    • No significant difference in terms of hospitalizations or incidence of plasmapheresis ≤3 months of treatment initiation in pts treated with or without rituximab
  • Cohort B (n = 1,028)
    • Adjusted difference in survival between pts who received rituximab monotherapy or multi-agent chemotherapy was not statistically different (HR, 0.91; 95% CI, 0.79–1.04)
    • Numbers of pts requiring hospitalization, transfusion, or plasmapheresis ≤3 months after starting treatment were significantly less in the rituximab monotherapy group
  • Cohort C (n = 599)
    • Purine-based therapy more common in pts with WM histology; alkylators more common to treat nodal LPL
    • Use of purine analogues reduced over time: 1999–2003 = 71% of pts; 2008–2013 = 35% of pts
    • Rituximab use was balanced between arms
    • No significant difference found in OS (HR, 1.10; 95% CI, 0.92–1.32)
    • No significant difference in terms of hospitalizations, transfusions, or plasmapheresis

The authors concluded that rituximab confers a significant survival benefit when used as part of first-line treatment for WM/LPL. Furthermore, therapy with rituximab as a single-agent has a more favorable toxicity profile and a similar survival compared with combination strategies and so “remains an attractive option for older patients who do not have a strong indication for cytotoxic chemotherapy”.


Comparative data on immunochemotherapy regimens for Waldenström macroglobulinaemia/lymphoplasmacytic lymphoma (WM/LPL) are lacking. We analysed overall survival (OS), risk of hospitalizations, transfusions and plasmapheresis in a population-based cohort of patients ≥65 years old initiating WM/LPL therapy in 1999-2013. To minimize bias, we applied a propensity score-based causal inference method. We conducted three analyses of: patients treated with or without rituximab, patients treated with rituximab monotherapy or with combination immunochemotherapy, and regimens based on classic purine analogues or alkylators. Among 1310 patients, 78·5% received rituximab. Patients who received rituximab had significantly better OS [hazard ratio (HR) 0·62, 95% confidence interval (CI) 0·55-0·71] and lower risk of transfusions (risk difference -3·3%, 95% CI -6·3 to -0·3) than those who did not, without a significant difference in hospitalizations or plasmapheresis. We observed no significant difference in OS (HR 0·91, 95% CI 0·79-1·04) between rituximab monotherapy and combination immunochemotherapy, but toxicity outcomes were lower with rituximab alone. Neither survival (HR 1·10, 95%CI 0·92-1·32) nor toxicity outcomes differed significantly between regimens based on purine analogues or alkylators. The survival advantage strongly supports rituximab as part of upfront therapy for WM/LPL, whereas regimens with either purine analogues or alkylating agents result in similar outcomes.

  1. Olszewski A.J. et al. Comparative outcomes of immunochemotherapy regimens in Waldenström macroglobulinaemia. British Journal of Haematology. 2017 Jul 5. DOI: 10.1111/bjh.14828. [Epub ahead of print].