Table 1 Summary of clinical responses... | American Society of Hematology

Table 1

Summary of clinical responses observed with ribavirin treatment

Pt no.	Age/sex	WHO classification	Cytogenetics	FLT3 mutation	NPM1 mutation	Prior Tx	Disease status baseline	Treatment duration, d	OS, d	Best response	Peripheral absolute blast count, ×10⁹/L		Bone marrow blast (%)		Max. dose level ribavirin, mg	Plasma levels ribavirin at max dose, μM
Pt no.	Age/sex	WHO classification	Cytogenetics	FLT3 mutation	NPM1 mutation	Prior Tx	Disease status baseline	Treatment duration, d	OS, d	Best response	Before Tx	At best response	Before Tx	At best response	Max. dose level ribavirin, mg	Plasma levels ribavirin at max dose, μM
1	69/F	tAML	Complex*	n/a	n/a	None	Untreated	60	83	SD	1.73	0.51	30	20	1400	n/a
3	46/M	NOC	Normal	ITD	N	2× ind; 4× cons reind	Relapsed/ refractory	137	137	SD	47.4	15.5	94	n/a	2800	5
5	54/M	RGA	46, XY, t(6;11) (q27;q23)	n/a	n/a	2× ind; 1× cons; haploT	Relapsed	27	27	PD	0.04	3.6	90	n/a	1000	n/a
6	77/F	NOC	Normal	ITD	Y	None	Untreated	142	276+	BR	23.3	0	95	29	2000	26.2
7	60/M	RGA	46, XY, t(9;11) (p22;q23)	ITD	N	1× ind; 1× cons	Relapsed	104	120	PR*	0	0	1	1	1000	9.3
8	70/M	NOC	45, X,−Y	ITD	Y	1× ind;1× cons; autoPBSCT	Relapsed	93	176+	PRi	0.06	0	65	10	2000	17
9	44/M	NOC	n/a	TKD	Y	1× ind;4× cons;2× reind	Relapsed/ refractory	33	33	PD	4.76	3.46	n/a	n/a	1400	36
10	56/F	NOC	Normal	ITD	N	1× ind; 4× cons	Relapsed	119	148+	BR	12.1	0.6	88	46	2000	14.8
11	77/M	MLD	Normal	ITD	N	None	Untreated	111+	111+	CR	0.06	0	72	4	1000	14.7
12	79/F	RGA	46, XX, inv(16) (p13q22)	ITD	N	None	Untreated	19	104+	SD	0.78	n/a	85	90	1000	15.3
13	72/M	MLD	Normal	ITD	Y	Low Ara-C + sorafenib	Relapsed	32	39	SD	26.1	32.6	95	95	2000	14.2

Pt no.	Age/sex	WHO classification	Cytogenetics	FLT3 mutation	NPM1 mutation	Prior Tx	Disease status baseline	Treatment duration, d	OS, d	Best response	Peripheral absolute blast count, ×10⁹/L		Bone marrow blast (%)		Max. dose level ribavirin, mg	Plasma levels ribavirin at max dose, μM
Pt no.	Age/sex	WHO classification	Cytogenetics	FLT3 mutation	NPM1 mutation	Prior Tx	Disease status baseline	Treatment duration, d	OS, d	Best response	Before Tx	At best response	Before Tx	At best response	Max. dose level ribavirin, mg	Plasma levels ribavirin at max dose, μM
1	69/F	tAML	Complex*	n/a	n/a	None	Untreated	60	83	SD	1.73	0.51	30	20	1400	n/a
3	46/M	NOC	Normal	ITD	N	2× ind; 4× cons reind	Relapsed/ refractory	137	137	SD	47.4	15.5	94	n/a	2800	5
5	54/M	RGA	46, XY, t(6;11) (q27;q23)	n/a	n/a	2× ind; 1× cons; haploT	Relapsed	27	27	PD	0.04	3.6	90	n/a	1000	n/a
6	77/F	NOC	Normal	ITD	Y	None	Untreated	142	276+	BR	23.3	0	95	29	2000	26.2
7	60/M	RGA	46, XY, t(9;11) (p22;q23)	ITD	N	1× ind; 1× cons	Relapsed	104	120	PR*	0	0	1	1	1000	9.3
8	70/M	NOC	45, X,−Y	ITD	Y	1× ind;1× cons; autoPBSCT	Relapsed	93	176+	PRi	0.06	0	65	10	2000	17
9	44/M	NOC	n/a	TKD	Y	1× ind;4× cons;2× reind	Relapsed/ refractory	33	33	PD	4.76	3.46	n/a	n/a	1400	36
10	56/F	NOC	Normal	ITD	N	1× ind; 4× cons	Relapsed	119	148+	BR	12.1	0.6	88	46	2000	14.8
11	77/M	MLD	Normal	ITD	N	None	Untreated	111+	111+	CR	0.06	0	72	4	1000	14.7
12	79/F	RGA	46, XX, inv(16) (p13q22)	ITD	N	None	Untreated	19	104+	SD	0.78	n/a	85	90	1000	15.3
13	72/M	MLD	Normal	ITD	Y	Low Ara-C + sorafenib	Relapsed	32	39	SD	26.1	32.6	95	95	2000	14.2

Tx indicates transplantation; M, male; F, female; d, days; complex*, 46, XX, del(5)(q13q35)/45, XX,+1, dic(1;11)(p11;q13), t(1;3)(p13;q26), −4, der(5)t(5;11)(q31;q13), der(?16)t(4;?16)(q12;?q10), der(19)t(19;?)(q13.4;?); tAML, therapy-related AML; RGA, AML with recurrent genetic abnormality; NOC, AML not otherwise categorized; MLD, AML with multilineage dysplagia; ITD, internal tandem duplication; TKD, tyrosine kinase domain point mutation; ind, induction; cons, consolidation; haploT, haploidentical allotransplantation; autoPBSCT, autologous peripheral blood stem cell transplantation; OS, overall survival; CR, complete remission; SD, stable disease; PD, progressive disease; BR, blast response; PRi, partial remission with incomplete blood count recovery; PR*, disappearance/regression of skin lesions; n/a, not available; +, continuing; Y, yes; N, no.

It is noteworthy that patient 3 entered the trial with a diagnosis of M4 AML, but this was later modified to M1. Patient 3 continued treatment because he had elevated eIF4E levels (Figure 1C), which is unusual for M1 AML.¹⁴ Patient 3 weighed 160 kg, and thus even at 2800 mg/day ribavirin, achieved plasma concentrations of only 5 μM. In contrast, other patients achieved higher concentrations of ribavirin at lower doses.

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