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

On 5^th 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”.

Abstract:

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.