Prognostic Factors for Survival After 2-CdA-Based Therapy for Symptomatic Waldenström Macroglobulinemia (WM) Stratify Patients Into Low- and High-Risk Groups.
Authors: Thomas Sheeba K , Feng Lei , Delasalle Kay B , Wang Michael , Shah Jatin J , Orlowski Robert Z , Alexanian Raymond , Weber Donna M 
Published: October 2019

Abstract 1668

Poster Board I-694

Introduction

Retrospective studies performed by others between 2001-2009, have identified various prognostic factors for survival among patients with symptomatic WM. These include hemoglobin, platelet count, albumin, and β2-micrglobulin (β2M) at varied cutoffs, as well as gender, age, IgM level, monoclonal (M) protein level, hyperviscosity syndrome, prior therapy, presence of splenomegaly/organomegaly, stage as defined by the International Staging System for multiple myeloma (ISSMM) and risk score as defined by the International prognostic scoring system for Waldenström macroglobulinemia (IPSSWM).

Methods

We retrospectively analyzed our experience with 80 previously untreated patients with symptomatic WM who participated on one of four 2-chlorodeoxyadenosine (2-CdA)-based clinical trials between 3/90-5/02, to identify factors predicting overall survival. Patients received either 2 consecutive 4-6 week courses of 2-CdA at 1.5 mg/m2 subcutaneously three times daily for 7 days (d) alone (10 patients), with prednisone (Pred) at 60 mg/m2 orally (po) d1-7 (21 patients), with cyclophosphamide (Cy) at 40 mg/m2 po twice daily (bid) for 7d (31 patients), or with Cy at 40 mg/m2 po bid for 7d + rituximab (Rit) at 375 mg/m2 intravenously weekly for 4 weeks (18 patients). Overall survival (OS) from the start of therapy was censored as of April 1, 2009. Predictive factors identified by multivariate analysis in other retrospective studies, as well as other clinically relevant factors, were evaluated.

Results

Median age of patients was 62.1 years (range 35.9-80.1), and 41 were male. Median hemoglobin was 10 g/dL (5.6-15.6), platelet count was 243 K/μL (26-654), albumin was 4.1 g/dL (2.5-5.4), and β2M was 3.3 mg/L (1.4-15.9). Splenomegaly and lymphadenopathy (≥ 2 cm) were present in 29.1% and 28.8% of patients, respectively. By ISSMM, 38 patients were Stage I, 29 were Stage II, and 13 were Stage III. By IPSSWM, 24 patients were low-risk, 45 were intermediate-risk, and 11 were high-risk. With a median follow-up of 9.9 years (yrs; range 0.9-16.8), median OS for all patients was 8.9yrs (0.1 yrs-not reached (NR)). By univariate analysis, age <65y, primary therapy (2CdA/Cy/Rit >2CdA/Cy > 2CdA >2CdA/Pred), albumin ≥3.5 g/dL, B2M <3.5 mg/L vs. 3.5-5.5 mg/L vs. >5.5 mg/L, ISSMM and IPSSWM, were all significant (p< 0.05). In multi-covariate models, primary therapy (2CdA/Cy/Rit vs. other 2CdA regimens), age, ISSMM, and IPSSWM remained significant. Removing the 2CdA/Pred cohort (which had the poorest OS) from the analysis of primary therapy, the trend toward superior OS with 2CdA/Cy/Rit vs. 2CdA+2CdA/Cy persisted (NR vs. 9.2 yrs), but did not reach statistical significance (p=0.12). Median OS for patients of age <65 yrs was 15.4 yrs compared with 6.2 yrs for those age ≥65 yrs (p=0.03). ISSMM stage I disease was associated with a median OS of 12.5 yrs, while stage II was 6.3 yrs, and stage III was 6.0 yrs (p=0.02). By comparison, median OS has not yet been reached among those classified as having low-risk disease by IPSSWM, while the intermediate-risk group has a median OS of 6.5 yrs, and the high-risk group has a median OS of 5.8 yrs (p=0.03).

Conclusion

Both ISSMM and IPSSWM are predictive of overall survival among patients with symptomatic WM treated first-line with 2CdA-based regimens. In our experience, rates of 10 year OS were better stratified by age, <65 yrs (62%) vs. ≥65 yrs (30%), and IPSSWM risk score, low (63%) vs. intermediate (46%) vs. high (24%), than by ISSMM stage (stage I [58%] vs. stage II [49%] vs. stage III [0%]). Novel therapeutic strategies are needed to improve the survival of patients with WM who are of older age, or who have high-risk IPSSWM or higher stage ISSMM disease. Longer follow-up is needed to confirm the trend toward improved survival seen with the addition of rituximab to 2CdA-based therapy.

Disclosures

No relevant conflicts of interest to declare.