Yttrium-90 ibritumomab tiuxetan in the treatment of non-Hodgkin lymphoma

Figures & data

Figure 1 Scheme for administration of rituximab followed by injection of Y90 ibritumomab tiuxetan.

Note: The curved arrow indicates that ibritumomab dose is given on the same day as the rituximab.
Abbreviation: Y90, yttrium-90.

Table 1 Toxicities from key multicenter clinical trials evaluating single-agent Y90 ibritumomab tiuxetan in relapsed/refractory non-Hodgkin lymphoma (rows 1 and 2) and consolidation with Y90 ibritumomab tiuxetan after response to induction chemotherapy

Reference	Design	Patients (n)	Y90 ibritumomab tiuxetan dosing	WBC nadir (baseline, μL)	Platelet nadir (baseline, μL)	Neutrophil nadir time	Platelet nadir time	Grade 3/4 granulocytopenia	Grade 3/4 anemia	Grade 3/4 thrombocytopenia	Comments
Knox et al^Citation22	Phase I	18	3–4 patients per cohort treated with dose levels 13.5, 20, 30, 40, and 50 mCi/kg Y90 ibritumomab tiuxetan	1.7 (5.6)	40 (177)	5.1 weeks	4.8 weeks	72.20%	22.20%	77.80%	3/4 patients at 40 mCi dose received G-CSF
Witzig et al^Citation23	Phase I	15	0.4 mCi/kg Y90 ibritumomab tiuxetan	1.1 (4.0) granulocyte count	49.5 (226)	50	43	NR	NR	NR	3 patients received G-CSF, 10 patients received platelet transfusion
Morschhauser et al^Citation29	Phase III	409 (204 Y90 ibritumomab tiuxetan treated)	Chemotherapy followed by 0.4 mCi/kg Y90 ibritumomab tiuxetan	NR	NR	NR	NR	66.70%	3.40%	60.80%	Phase III consolidation study, RIT given to responders post induction

Abbreviations: G-CSF, granulocyte colony-stimulating factor; NR, not reported; RIT, radioimmunotherapy; WBC, white blood cell count; Y90, yttrium-90.

Table 2 Results of key studies evaluating Y90 ibritumomab tiuxetan in relapsed/refractory NHL subtypes

Reference	Primary RIT	Comparator	Patients (n)	PFS (months)	OS months	Overall response (%)	CR rate (%)	Disease(s)	Comments
Knox et al^Citation22	Ibritumomab dose levels 13.5, 20, 30, 40, and 50 mCi/kg	NA	18	NA	NA	72	32	Relapsed/refractory low grade/ intermediate NHL	Initial Phase I/ll dose escalation
Witzig et al^Citation23	Ibritumomab 0.4 mCi/kg	NA	51	12.9	NA	67	27	Relapsed/refractory low grade/ indolent NHL, MCL	0.4 mCi/kg dose, 0.3 mCi/kg given for platelet counts 100,000-150,000 pL
Wiseman et al^Citation24	Ibritumomab 0.4 mCi/kg	NA	30	9.4	NA	83	37	Advanced, relapsed or refractory, low-grade, follicular, or transformed B-cell NHL	Patients with baseline platelet counts 100-150 mL
Witzig et al^Citation38	Ibritumomab 0.4 mCi/kg	NA	57	6.8 (8.7 for responders)	NA	74	15	Relapsed/refractory low grade/ indolent transformed NHL	Rituximab-refractory patients
Witzig et al^Citation39	Ibritumomab 0.4 mCi/kg	Rituximab	143	14.2 versus 12.1	NA	80 versus 56	30 versus 16	Relapsed/refractory low grade/ indolent transformed NHL
Morschhauser et al^Citation45	Ibritumomab 0.4 mCi/kg	NA	104	5.9	21.4	52	24	Relapsed/refractory DLBCL	Results divided by a priori strata
Wang et al^Citation51	Ibritumomab 0.4 mCi/kg	NA	34	6	21	31	15.5	Relapsed/refractory MCL	Pretreated MCL patients; various subset analyses

Abbreviations: CR, complete response (response determined by individual study criteria using cross sectional imaging); DLBCL, diffuse large B-cell lymphoma; NHL, non-Hodgkin lymphoma; OS, overall survival; PFS, progression-free survival; MCL, mantle cell lymphoma; RIT, radioimmunotherapy; NA, not available; Y90, yttrium-90.

Table 3 Results of key studies evaluating Y90 ibritumomab tiuxetan in aggressive NHL subtypes

Reference	Treatment	Patient population	Patients (n)	PFS*	OS*	ORR (%)	CRR (%)	Comment(s)
Tsimberidou et al^Citation89	Ibritumomab	Richter syndrome	7	NA	NA	0	0	Case series, no responses noted
Morschhauser et al^Citation45	Ibritumomab	DLBCL	104	5.9 months	21.4 months	52	24	Results divided by a priori strata
Zinzani et al^Citation47	Ibritumomab consolidation/FM	DLBCL	20	2 years (75%)	2 years (95%)	100	95	Elderly front-line trial
Wang et al^Citation51	Ibritumomab	Relapsed/ refractory MCL	34	6 months	21 months	31	15.5	Pretreated MCL patients; various subset analyses
Zinzani et al^Citation46	Ibritumomab consolidation R-CHOP	DLBCL	55	2 years (85%)	2 years (86%)	NA	NA	50% of PRs obtained CRs with RIT
Yang et al^Citation48	Ibritumomab consolidation R-CHOP	DLBCL bulky stage I/II disease	21	3 years (75%)	3 years (85%)	80.9	76.1	DLBCL consolidation no comparator
Beaven et al^Citation61	Ibritumomab bortezomib	MCL and low- grade NHL	12	6.4 months	Median survival 24 months	50%	42%	4/6 patients with response were MCL
Smith et al^Citation49	Ibritumomab consolidation R-CHOP	MCL previously untreated	56	34.2 months median FFS	5 years (73%)	82	55	Eastern Cooperative Oncology Group Study EI499
Arranz et al^Citation50	Ibritumomab consolidation/ R-HyperCvAD	MCL	30	4 years, (52%)	4 years, (81%)	97	77 (intention to treat) 96% in patients completing treatment	R-HyperCVAD, Zevalin consolidation

Notes: *Median PFS or OS, respectively where calculated in the study, percentages calculated at a set period of time are listed as the period of time followed by the PFS/OS percentage in parentheses.

Abbreviations: CR, complete response; CRR, complete response rate; DLBCL, diffuse large B-cell lymphoma; FFS, failure-free survival; NHL, non-Hodgkin lymphoma; OS, overall survival; PFS, progression-free survival; FM, fludarabine/mitoxanthrone chemotherapy; MCL, mantle cell lymphoma; PR, partial response: RIT, radioimmunotherapy; ORR, overall response rate; R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone; NA, not available; R-HyperCVAD, rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with cytarabine, and methotrexate; Y90, yttrium-90.

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