First-line treatment of chronic lymphocytic leukemia: role of alemtuzumab

Figures & data

Table 1 Efficacy of alemtuzumab compared to other first-line single-agent regimens in chronic lymphocytic leukemia

Drug	Author	Trial phase	No. of pts	Max dose	ORR (%)a	CR (%)a	Median PFS (months)	Median OS (months)	% OS at n years
Alemtuzumab iv	Hillmen et al^Citation59	III	149	30 mg tiw iv, 12 weeks	83	24	14.6	nr	–
Alemtuzumab sc	Lundin et al^Citation53	II	41	30 mg tiw sc, 18 weeks	87	19	nr	nr	–
	Karlsson et al^Citation66						14 (TTP) 28 (TTTF)	–	–
Fludarabine iv	Rai et al^Citation87	III	170	25 mg/m^2 day 1–5, q28d, 6 cycles	63	20	20 (TTP)	66	–
	Eichhorst et al^Citation88b	III	182	25 mg/m^2 day 1–5, q28d, 6 cycles	82.9	6.7 18.3 uCR	20	nr	80.7 at 3 years
	Catovsky et al^Citation9	III	181	25 mg/m^2 day 1–5 iv or 40 mg/m^2 day 1–5 po, q28d, 6 cycles	80	15	23	–	52 at 5 years
	Flinn et al^Citation89	III	137	25 mg/m^2 day 1–5, q28d, 6 cycles	59.5	4.6	19.2	nr	80 at 2 years
	Eichhorst et al^Citation38c	III	87	25 mg/m^2 day 1–5, q28d, 6 cycles	72	7	19	46	–
Bendamustine iv	Knauf et al^Citation90	III	162	100 mg/m^2 d1–2, q28d, 6 cycles	68	31	21.6	–	–
Cladribine iv	Robak et al^Citation91	III	126	0.12 mg/kg d1–5, q28d, 6 cycles	78	21	23.5	51.2	–
Chlorambucil po	Hillmen et al^Citation59	III	148	40 mg/m^2, q28d, 12 cycles	55	2	11.7	nr	–
	Rai et al^Citation88	III	181	40 mg/m^2, q28d, 12 cycles	37	4	14 (TTP)	56	–
	Robak et al^Citation92	III	103	12 mg/m^2 d1–7, 6 cyclese	57	12	17	45
	Catovsky et al^Citation9	III	324	10 mg/m^2 d1–7, 12 cycles	72	7	20	–	59 at 5 years
	Knauf et al^Citation90d	III	157	0.8 mg/kg d1, d1 + 15, 6 cycles,	31	2	8.3	–	–
	Eichhorst et al^Citation38c	III	98	0.4 mg/kg d1, d1 + 15, 12 cycles, dose increased by 0.1 mg/kg each cycle up to 0.8 mg/kg	51	0	18	64	–
Rituximab iv	Hainsworth et al^Citation93	II	44	375 mg/m^2, 1 × /week, 4 weeks	58	9	18.6	–	–

a Response assessed according to NCI Working Group Criteria 1996⁹⁴,

b inclusion limited to patients ≤65 years of age,

c inclusion limited to patients >65 years of age,

d inclusion limited to patients <75 years of age,

e administered in conjunction with prednisone.

Abbreviations: d, day; CR, complete response. iv, intravenous. nr, not reached; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; Pts, patients; q28d, administered every 28 days/4-weekly; sc, subcutaneous; TTP, time to progression; TTTF, time to treatment failure; uCR, unconfirmed CR.

Table 2 Alemtuzumab-based combinations in current clinical trials (previously untreated chronic lymphocytic leukemia)

Drug	Trial identifier	Author	Trial Phase	No. of pts	Maximum dose	ORR (%)	CR (%)
FluCam (high risk) or FC (low risk)	GIMEMA Multicenter LLC0405	Mauro et al^Citation68	II	74	Fludarabine 30 mg/m^2 iv + alemtuzumab 30 mg iv, d1–3, q28d,4 cycles (high risk)	71	30
					or
					Fludarabine 30 mg/m^2 iv + cyclophosphamide 250 mg/m^2, d1–3, q28d, 6 cycles (low risk)	95	57
Cam-Pred (high-risk only)	NCRI CLL206	Pettitt et al^Citation73	II	17	Alemtuzumab 30 mg tiw up to 16 weeks + methylprednisolone 1.0 g/m^2 d1–5 weeks 1, 5, 9, 13	n k	37
Alemtuzumab + rituximab at early stage (high-risk only)	nk	Zent et al^Citation78	II	30	Alemtuzumab 30 mg tiw + rituximab 375 mg/m^2 qwk, 4 weeks	90	37
Alemtuzumab + rituximab	nk	Frankfurt et al^Citation77	II	21	Alemtuzumab 30 mg tiw, 17 weeks + rituximab 375 mg/m^2 every other week, 8 times	90	75
CFAR (high risk only)	nk	Wierda et al^Citation76	II	60	Fludarabine 20 mg/m^2 d3–5 + cyclophosphamide 200 mg/m^2 d3–5 + rituximab 375–500 mg/m^2 d2 + alemtuzumab 30 mg tiw, q28d,4 cycles	94	69

Abbreviations: d, day; nk, unknown; q28d, administered every 28 days/4-weekly; qwk, administered every week; tiw, administered 3 times per week.

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