Simplified Risk Stratification Model for Patients With Waldenström Macroglobulinemia

Author(s): Saurabh Zanwar, MD, MBBS1; Jennifer Le-Rademacher, PhD2; Eric Durot, MD3; Shirley D’Sa, MD, FRCP, FRCPath4; Jithma P. Abeykoon, MD1; Patrizia Mondello, MD, PhD1; Shaji Kumar, MD1; Shayna Sarosiek, MD5; Jonas Paludo, MD1; Saurabh Chhabra, MD, MBBS6; Joselle M. Cook, MBBS1; Ricardo Parrondo, MD7; Angela Dispenzieri, MD1; Wilson I. Gonsalves, MD1; Eli Muchtar, MD1; Sikandar Ailawadhi, MD7; Robert A. Kyle, MD1; S. Vincent Rajkumar, MD1; Alain Delmer, MD3; Rafael Fonseca, MD6; Morie A. Gertz, MD1; Steven P. Treon, MD, PhD5; Stephen M. Ansell, MD, PhD1; Jorge J. Castillo, MD5; Prashant Kapoor, MD1
Source: https://doi.org/10.1200/JCO.23.02066

Dr. Anjan Patel's Thoughts

Maybe it’s me, but I find these prognostic/risk stratification tools helpful especially when they are simple. This study shows that LDH, albumin, age of 66-75 all were strongly prognostic. This can be easily applied in the clinic to our patients when advising the risk of the disease and the need for potential therapy. Recall that there is a growing armamentarium of drugs in this disease, as well as clinical trials, within our practice.

PURPOSE

Patients with Waldenström macroglobulinemia (WM) have disparate outcomes. Newer therapies have emerged since the development of International Prognostic Scoring System, and MYD88L265P mutation is now frequently assessed at diagnosis, warranting reexamination of the prognostic parameters.

PATIENTS AND METHODS

We reviewed records of 889 treatment-naïve patients with active WM, consecutively seen between January 01, 1996, and December 31, 2017, to identify clinical predictors of overall survival (OS) in univariate analyses. Patients with complete data for the parameters significant on the univariate analyses (n = 341) were included in a multivariable analysis to derive a prognostic model, subsequently validated in a multi-institutional cohort.

RESULTS

In the derivation cohort (n = 341), age (hazard ratio [HR], 1.9 [95% CI, 1.2 to 2.1]; P = .0009), serum lactate dehydrogenase (LDH) above upper limit of normal (HR, 2.3 [95% CI, 1.3 to 4.5]; P = .007), and serum albumin <3.5 g/dL (HR, 1.5 [95% CI, 0.99 to 2.3]; P = .056) were independently prognostic. By assigning a score of 1 point each to albumin <3.5 g/dL (HR, 1.5) and age 66-75 years (HR 1.4) and 2 points for age >75 years (HR, 2.6) or elevated LDH (HR, 2.3), four groups with distinct outcomes were observed on the basis of the composite scores. Five-year OS was 93% for the low-risk (score 0), 82% for low-intermediate risk (score 1), 69% for intermediate-risk (score 2), and 55% for the high-risk (score ≥3; P < .0001) groups. In the validation cohort (N = 335), the model maintained its prognostic value, with a 5-year OS of 93%, 90%, 75%, and 57% for the four groups, respectively (P < .0001).

CONCLUSION

Modified Staging System for WM (MSS-WM), utilizing age, albumin, and LDH is a simple, clinically useful, and externally validated prognostic model that reliably risk-stratifies patients with symptomatic WM into four groups with distinct prognosis.

Author Affiliations

1Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN; 2Division of Clinical Trials and Biostatistics, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN; 3Department of Hematology, University Hospital of Reims and UFR Médecine, Reims, France; 4University College of London, London, United Kingdom; 5Dana-Farber Cancer Institute, Boston, MA; 6Division of Hematology, Mayo Clinic, Scottsdale, AZ; 7Division of Hematology, Mayo Clinic, Jacksonville, FL

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