Good Profile of Efficacy/Tolerance of Bortezomib or Idelalisib in Waldenström Macroglobulinemia Associated with Acquired Von Willebrand Syndrome

Figures & data

Table 1 Laboratory Parameters at Diagnosis of Waldenström Macroglobulinemia

UPN	Age at Diagnosis (Years)	Monoclonal Gammapathy	Serum Immunoglobulin Values (g/L)	Bone Marrow Cytology and Immunophenotyping in Favor of WM	Mutation L265P of MYD88	CXCR4 Mutation	Marrow Cytogenetics
UP1	90	IgM kappa	IgM: 83.4	Yes	Positive	Positive	Normal
			IgG: 4.50			S338 CXCR4 WHIM like
			IgA: 0.82
UP2	70	IgM kappa	IgM: 72	Yes	Positive	Negative	Normal
			IgG: 5.3
			IgA: 0.2
UP3	79	IgM kappa	IgM:39	Yes	Positive	Negative	Normal
			IgA: 0.18
			IgG: 4.4
MEAN	77.5		IgM 62

Table 2 Laboratory Parameters at Diagnosis of AVWS Concomitant with Waldenström Macroglobulinemia

UPN	aPTT	Platelet occlusion time	FVIII:C	VWF:Ag	VWF:RCo	Concentration VWFpp (%)	Ratio VWFpp/VWFAg	Assessment Multimers VWF	anti–VWF antibodies
	N < 1.2 T	collagen-ADP & collagen-epinephrine				(55–148)	(> 2.8 group 0 & > 2.4 other group = increased VWF clearance)
		(seconds)	(%)	(%)	(%) activity
		ADP N 49–108	N 50–150	(O 42–140)	N O 40–125
		Epinephrine N 66–150		(No O 66–176)	Non O 49–163					ABO group
UP1	Prolonged	Prolonged	57	26	39	78	High 2.8	Yes	Neg	O+
UP2	Prolonged	>300/>300	21	28	27	78	High 3.4	Yes	Neg	A+
UP3	Prolonged 1.55	>300/>300	44	37	41	91	High 3.5	Normal pattern	Pos (un-interpretable)	O+
MEAN	all	>2N/>2N	43	28	32.2			All normal

Table 3 Laboratory Parameters During Treatment with Bortezomib-Based Therapy in Patients UP1 (41 Months in Duration) and UP2 (36 Months in Duration) and After Switching to Idelalisib Treatment (in UP1 from 44th^# Month, i.e., 3 Months After Stopping Bortezomib-Based Therapy and in UP2 from the 37th Month*, i.e., 1 Month After Stopping Bortezomib-Based Therapy). UP3 Received Only Idelalisib, and the Follow-Up Corresponds Only to the Outcome Under This Therapy

		Months After Chemotherapy
VWFAG (%)	0	1	6	12	24	36	37*	44^#	53	60	76**
UP1	26			120	67	173		224	207	134	208
UP2	19	21	65	57	39	42	60	100	STOP^&
UP3	37	62	52	64	101
VWFRCO (%)	0	1	6	12	24	36	37	44	53	60	72
UP1	39			117	61	110		134	150	114	150
UP2	27		73	65	36	48	47	79	STOP
UP3	41	55	52	64	90
VIIIF (%)	0	1	6	12	24	36	37	44	53	60	72
UP1	57			133	100	142		192	179	141	241
UP2	21	29	94		43	59	71	82	STOP
UP3	44	52	61	78	87
IGM g/L	0	1	6	12	24	36	37	44	53	60	72
UP1	83			44	37	13		12	10	7.3	3.9
UP2	75	63	24	23	54	50	42	50	STOP
UP3	39	25	17	12	11.7
aPTT N< 1.2 sec	0	1	6	12	24	36	37	44	53	60	75
UP1	1,44			N	N	N		N	N	N	N
UP2	1.57	1.51	N	N	1.4	1.28	1.25	1.23
UP3	1.55	1.35	1.28	1.27	1.2

Notes: ^&Date of idelalisib stop in UP1. **UP2 has a very long follow-up (>6 years) and is still on therapy.