Modern Therapies, Younger Age Predict Improved Outcomes in Waldenström Macroglobulinemia

Younger patients who are diagnosed early with Waldenström macroglobulinemia (WM) and have a low risk profile have excellent outcomes in the era of immunotherapy and targeted therapies, according to a new report.

The study, which focused on patients aged 55 and younger, was published in the American Journal of Hematology.

WM is typically diagnosed at an advanced age; the median age at diagnosis is 70. Because of this, age plays a significant role in a patient’s prognosis; it’s one of several factors included in the International Prognostic Scoring System for WM (IPSSWM), along with hemoglobin and platelet count, serum β2-microglobulin, and serum monoclonal IgM values. That scoring system is a decade old and built on a data set in which only 4% of patients received the monoclonal antibody rituximab (Rituxan).

A more recent revision to the scoring system attempted to account for advances in therapy. Its cohort of patients were typically treated with rituximab-based chemo-immunotherapy or proteasome inhibitors. The revised model, known as rIPSSWM, stratified patients based on age, albumin, serum β2-microglobulin and LDH, among other factors.

Though therapy and risk stratification are improving for these patients, a team of Italian investigators including corresponding author Marzia Varettoni, MD, of Fondazione IRCCS Policlinico San Matteo, wanted to gain a better understanding of the extent to which these changes impact the youngest group of patients. According to data from the United States, just 1 in 10 patients with WM is diagnosed at an age younger than 50. Varettoni and colleagues decided to assess treatment, risk stratification, and life expectancy among patients who are diagnosed with WM at age 55 or younger.

The study enrolled 160 patients, with a median age of 49 years, and an age range of 23-55. The patients were diagnosed between January 2000 and January 2019 and treated at 1 of 14 Italian treatment centers. Seventy percent of patients were asymptomatic at diagnosis, and 57% had received treatment by the median follow-up point of 5.6 years. Among those who received therapy, the majority (79%) received chemo-immunotherapy, 13% received chemo-free induction, and 8% received chemotherapy alone. A total of 19% of patients received the Bruton’s kinase inhibitor ibrutinib (Imbruvica) during the course of their treatment. Six percent of patients underwent autologous stem cell transplantation at relapse or progression.

The patients in the study helped elucidate significant differences between the initial IPSSWM and the revised version. In the initial scoring system, 63% were categorized as low risk, 27% as intermediate risk, and 10% as high risk. Under the revised scoring system, 92% were categorized as very low or low risk, and just 8% were diagnosed as intermediate risk.

Those categorized as high-risk using IPSSWM had a 5-year overall survival (OS) rate of 92.9%; those categorized as low or intermediate risk had a 100% 5-year OS.

While no patients were categorized as high-risk under the rIPSSWM scale, there was an OS difference between patients with intermediate risk (87.5%) and those with low or very low risk (100%).

“Early diagnosis, reflected by the high proportion of asymptomatic patients, the absence of high-risk features in symptomatic patients, and the high efficacy of modern treatments are the main determinants of the excellent outcome in young WM patients,” Varettoni and colleagues concluded.

Notably, early diagnosis appears to be more common. The authors noted that the second decade of the study saw a higher number of diagnoses compared to the first. Absent epidemiological evidence that cases increased, the authors attribute the uptick to greater awareness of the disease and increasing use of bone marrow biopsies in the diagnostic workups of young patients with asymptomatic serum IgM monoclonal gammopathy.

“This hypothesis is supported by the higher proportion of asymptomatic WM patients observed in this study as compared to previous reports,” they said.

Reference

Varettoni M, Ferrari A, Frustaci AM, et al. Younger patients with Waldenström Macroglobulinemia exhibit low risk profile and excellent outcomes in the era of immunotherapy and targeted therapies. Am J Hematol. Published online August 11, 2020. doi:10.1002/ajh.25961