Does early disease progression predict survival after first line-treatment of Waldenström macroglobulinemia?

Abstract

In symptomatic Waldenström macroglobulinemia (sWM) patients, prognosis is assessed with the international prognostic scoring system (IPSSWM). In follicular lymphoma and other B-cell and T-cell lymphomas, disease progression within 24 months (POD24) or (in patients without POD24) after 24 months has been proposed as the start date for stratifying subsequent survival. In the present report, we assessed in a large series of 472 sWM patients, the prognostic value of this new dynamic endpoint already reported in many other lymphomas subtypes. The 3 year subsequent survival for patients with POD24 was 75% and 93% for patients without POD24. In sWM patients, departure from the proportional hazards assumption complicated this analysis. In patients without POD24, the median subsequent progression-free survival time of 43 months accounted for favorable outcome, whereas survival after progression was not influenced by the time to progression. In addition, sensitivity analysis showed that the baseline IPSSWM score also influenced survival after POD24. In sWM patients, we conclude that the apparent difference in survival after POD24 or the 24 months time-point (in patients without POD24) is mainly explained by the prolonged subsequent progression free survival of latter patients. Indeed, the mortality after progression is not influenced by the time to this event.

Keywords: Waldenström macroglobulinemia; progression; survival.

FIGURE 1

Survival from 24 months onwards or after a risk‐defining event (progression or relapse before 24 months) in patients with Waldenström macroglobulinemia who received first‐line therapy. For patients with a persistent response at 24 months, plots of subsequent progression‐free survival after 24 months and survival after subsequent relapse (108 patients) are shown. Patients with a persistent response at 24 months (242 patients without POD24): (A) Subsequent survival (3‐year estimate: 93%; 95% CI, 89%–97%). Patients with relapse or progression before 24 months (129 patients with POD24): (B) Subsequent survival (3‐year estimates: 75%; 95% CI, 67%–83%). Patients with a persistent response at 24 months: (C) Subsequent progression free survival after 24 months (3‐year estimate: 54%; 95% CI, 47%–61%) and (D) Survival after late (after 24 months) relapse or progression (3‐year estimate: 84%; 95% CI, 77%–91%). Note: the difference in survival after progression occurring within 24 months of first treatment initiation (B) or more than 24 months after the first treatment initiation (D) was not significant (p = 0.26), and the hazard ratio did not change over time (data not shown)