Risk stratification in Waldenström macroglobulinemia

Figures & data

Figure 1. Survival rates of patients with IgM monoclonal gammopathy of undetermined significance and Waldenström macroglobulinemia.

Overall survival recorded in (A) 207 patients with IgM monoclonal gammopathy of undetermined significance, (B) 217 patients with A-WM and (C) 274 patients with S-WM compared with the corresponding survival of the general population, comparable for age, gender and calendar years of observation. A-WM: Asymptomatic Waldenström macroglobulinemia; IgM-MGUS: IgM monoclonal gammopathy of undetermined significance; SMR: Standardized mortality ratio; S-WM: Symptomatic Waldenström macroglobulinemia.Reproduced with permission from [31]

Figure 2. Survival after first treatment initiation according to subgroups defined by the International Scoring System for Waldenström Macroglobulinemia.

Int: Intermediate.

Reproduced with permission from [9]

Table 1. Survival estimates according to main prognostic factors in Waldenström macroglobulinemia.

Characteristic	Cutoff value	Prognostic information (median survival or HR)
		Treated patients only	All patients
Advanced age	60 years	42 versus 120 months [3]	42 versus 96 months [3]
	65 years	56–88 versus 141–172 months [9,33]; HR = 2.5 [8]	51 versus 87 months [5] 80 versus 209 months [4]
	70 years	27 versus 85 months [6]; HR = 2 [7]
Low hemoglobin concentration	9 g/dl	40 versus 78 months [6]
	10 g/dl	32 versus 73 months [3]; 90 versus 116 months [3]; HR = 1.4 [8]	31 versus 72 months [3]
	10.5 g/dl		84 versus 209 months [4]
	11.5 g/dl	72 versus 123 months [9]
	12 g/dl	HR = 1.9 [7]	49 versus 107 months [5]
Low platelet count	100 × 10^9/mm^3	51–55 versus 90–107 months [9,32,33]
	150 × 10^9/mm^3	33 versus 75 months [3]; HR = 1.6 [8]	30–40 versus 67–72 months [3,5]
Low WBCC	4 × 10^9/mm^3	36 versus 66–70 months [3]; HR = 1.5 [8]	30–42 versus 51–66 months [3,5]
High B2M	3 mg/l	63 versus 122 months [9]; HR = 2.5 [7]
	4 mg/l	79 versus 115 months [4]
	ULN		84 months versus NR [4]
	Linear	HR = 1.4 [8]
Low serum albumin concentration	40 g/l	HR = 2 [8]	49 versus 107 months [5]
	35 g/l	77–79 versus 106–112 months [9,33]; HR = 1.7 [7]
mIgM concentration	40 g/l	HR = 2.4 [7]
	45 g/l		84 versus 209 months [4]
	25 g/l		59 versus 68 months [5]
	70 g/l	49 versus 90 months [9]

^† All series included more than 200 patients except [3,6,33], which included 122–167 patients.

B2M: β2-microglobulin; HR: Hazard ratio; mIgM: Monoclonal IgM; NR: Not reached; ULN: Upper limit of normal range; WBCC: White blood cell count.

Table 2. The International Prognostic Scoring System for symptomatic Waldenström Macroglobulinemia requiring therapy.

Stratum	Score (number of adverse characteristics)	Total number of patients (%)	Median survival (months)	95% CI	Hazard ratio
Low	0 or 1 (except age)	155 (27)	142.5	120.30–195.71	1
Intermediate	Age or 2	216 (38)	98.6	81.70–137.2	2.36
High	3 or more	203 (35)	43.5	36.60–55.1	6.61

Data taken from [9]

Table 3. Adverse prognostic factors for treatment effectiveness in Waldenström macroglobulinemia.

Treatment	Patients	Adverse characteristics for response rate	Adverse characteristics for response duration	Adverse characteristics for subsequent survival	Ref.
Fludarabine	Previously treated (71 patients)	Short interval between the first treatment and the start of fludarabine		Hemoglobin <9.5 g/dl and platelet count <75 × 10^9/l	[78]
Fludarabine	Untreated and previously treated (182 patients)	Age ≥70 years	B2M ≥3 mg/l and mIgM <40 g/l (PFS)	Age ≥70 years, previous therapy, disease duration >1 year, B2M ≥3 mg/l, mIgM <40 g/l and CRP ≥1 mg/l	[7]
Fludarabine Cyclophosphamide	Untreated and previously treated (49 patients)		Age >65 years and mIgM <40 g/l	Age >65 years and mIgM <40 g/l	[19]
Fludarabine Cyclophosphamide Rituximab	Untreated and previously treated (1 line; 43 patients)	High B2M concentration			[79]
Rituximab	Untreated and previously treated (58 patients)	Fcγ receptor IIIA(F/F) phenotype			[11]
Rituximab	Untreated and previously treated (51 patients)	mIgM ≥40 g/l and serum albumin <35 g/l	mIgM ≥40 g/l (TTP)	Serum albumin <35 g/l	[13]

B2M: β2-microglobulin; CRP: C-reactive protein; mIgM: Monoclonal IgM; PFS: Progression-free survival; TTP: Time to progression.

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