Comparative outcomes of immunochemotherapy regimens in Waldenström macroglobulinaemia

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.

Transfusion dependence, use of hospice services, and quality of end-of-life care in leukemia

“…This definition mirrors prior studies using Medicare data, with the exception that some analyses defined the anchoring window as 30 days before death only. [18][19][20][21] We found that such an anchoring produces incorrect results due to guarantee-time bias in TD ascertainment (supplemental Figure 1, available on the Blood Web site). To assess the sensitivity of our results and illustrate bias in prior studies, we repeated all analyses using alternative criteria: $3 transfusions within 60 days or $4 transfusions within 90 days.…”

“…23,24 We identified chemotherapy administration recorded in Medicare claims, as previously described, with the caveat that the use of oral agents (including palliative hydroxyurea, oral chlorambucil, or tyrosine kinase inhibitors) was not consistently observed. 21,24,25 Explanatory variables included patient's age, sex, race/ethnicity (according to Medicare files), marital status, receipt of Medicaid coinsurance (indicator of disability or poverty), county-level indicators of population size and poverty prevalence, the National Cancer Institute-modified Charlson comorbidity index (a weighted score of comorbidities associated with mortality, based on Medicare claims from 12 months preceding death or hospice enrollment), preexisting dementia, indicator of poor performance status (validated as a measure of self-reported functional status), histological type of leukemia, time from diagnosis to death, and year of death. 24,26,27…”

How we manage patients with Waldenström macroglobulinaemia

“…Its recommended use is in combination therapy, as response rates in monotherapy were modest [overall response rate (ORR) of 52%, and major response rate (MRR) of 27%, in 69 untreated and previously treated WM patients] (Dimopoulos et al , ; Gertz et al , ). However, single agent rituximab is used for frail patients with high comorbidities or when symptomatology is due to autoimmune activity of the paraprotein IgM (Olszewski et al , ).…”

Long survival in patients with Waldenström macroglobulinaemia diagnosed at a young age

“…With a 10‐year OS rate of 86% in young WM patients, one could argue that OS might not be an optimal outcome of interest in these patients. Not surprisingly, OS benefits have not been apparent with any intervention in population‐based or randomized studies (Olszewski et al , ; Dimopoulos et al , ). Despite the limitations of this study (i.e.…”