Lenalidomide: a brief review of its therapeutic potential in myelodysplastic syndromes

Figures & data

Table 1 The international prognostic scoring system (IPSS) (Greenberg et al 1997)

				Points
		0	0.5	1	1.5	2.0
BM blasts (%)		0–4	5–10		11–20	21–29
Number of cytopenias1		0–1	2–3
Cytogenetic category2		low	int	high
Risk group	Score
Low	0
Intermediate I	0.5–1
Intermediate II	1.5–2
High	≥ 2.5

1 Neutrophils <1800/μl, platelets <100.000/μl, hemoglobin <10g/dl

2 Good: normal, isolated del(5q), isolated del(20q), isolated –Y; poor: chromosome 7 abnormalities, complex abnormalities (≥ chromosomal abnormalities); intermediate: all others.

Table 2 Current treatment options in low- and intermediate-1 risk myelodysplastic syndromes (not covering all experimental therapies)

Blood transfusion (erythrocytes, platelets) Iron chelation therapy (deferasirox, deferoxamine, deferiprone) Danazol Pyridoxine Erythropoietin ± granulocyte colony-stimulating factor Valproic acid Antithymocyte Globulin and cyclosporine A Lenalidomide 5-Azacitidine Decitabine Low-dose cytarabine

Table 3 Comparison of clinical, biological, and molecular features between thalidomide and lenalidomide

	Thalidomide	Lenalidomide
Teratogenicity (animal model)	+	−
Inhibition of cytokine generation (TNF-α, IL-6)	+	+++
Stimulation of IL-10, IL-2, IFN-γ	+	+++
Antiangiogenesis Adverse events	+	++
Constipation	++	−
Polyneuropathy	++	−
Sedative effects	+++	−
Deep venous thrombosis	+	(+)*
T-cell costimulatory effect	+	++
Enhancement of NK-cell Cytotoxicity	+	+
Reduction in tumor growth in Vivo (SCID mice)	+	++

Abbreviation: NK, natural killer; IL, Interleukin; TNF, tumor necrosis factor; IFN, Interferon; SCID, severe combined immunodeficiency.

* DVT not a clinical problem in myelodysplastic syndromes, but important in multiple myeloma.

Table 4 Lenalidomide-MDS-001 trial – Chromosomal abnormalities and responses at a glance (List et al 2005)

Cytogenetic abnormality	No. of patients	Complete cytogenetic responses
del(5q31.1)	12	9(75%)
isolated	11	8
with trisomy 21	1	1
del(20)(q11.2)	2	0
T(1;22)(q21p11.2)	1	1
Other*	5	0
Total	20	10(50%)

* +19; +8; −X; t(3;3) (q21; q26.3); and complex

Table 5 Predictive factors for lenalidomide response at a glance (Lenalidomide-MDS-001 trial, total number of patients, n=43) (List et al 2005)

Variable	No. of patients	Erythroid response (%)	P-value
IPSS risk group			0.14
Low	22	15 (68)
Intermediate-1	16	8 (50)
Intermediate 2 or high	5	1 (20)
FAB classification			0.07
RA	20	15 (75)
RARS	13	6 (46)
RAEB(t)	9	3 (33)
CMML	1	0
Karyotype			0.007
del(5q31)	12	10 (83)
Normal	23	13 (57)
Other	8	1 (12)

Table 6 Hematological adverse events at a glance (Lenalidomide-001-trial, total number of patients, n = 43) (List et al 2005)

	Grade 1 or 2 (NCI)	Grade 3 or 4 (NCI)	All patients, all grades
Neutropenia	0	28 (65%)	28 (65%)
Thrombocytopenia	9 (21%)	23 (53%)	32 (74%)

Table 7 Responses in Lenalidomide-MDS-002 trial (Raza et al 2005)

Intent to treat (n = 215)	No. of patients (%)
Transfusion Independence	21.4%
Low-/Intermediate-1 patients (n = 169)
Transfusion Independence	25%
Minor response (>50% reduction of transfusion requirements)	18%
Total	43%

Table 8 Hematological adverse events leading to treatment interruption in the Lenalidomide-MDS-002-trial (Total number of patients, n = 215) (Raza et al 2005)

	All patients, all grades
Neutropenia	19%
Thrombocytopenia	15%

Table 9 Lenalidomide-MDS-003: Erythroid and cytogenetic response rates (List et al 2006)

Intent to treat (n = 148)	No. of patients (%)
Transfusion Independence	99 (67%)
>50% reduction of transfusion need (but not transfusion-free)	13 (9%)
Median haemoglobin increase	5.4 g/dl
Median interval to response	4.6 weeks
Overall cytogenetic response	73%
Complete cytogenetic response	45%

Table 10 Lenalidomide-MDS-003: Overview on hematological adverse events (List et al 2006)

Intent to treat (n = 148)	No. of patients (%)
Neutropenia (Grade 3 or 4)	55%
Thrombocytopenia (Grade 3 or 4)	44%
Median duration of treatment interruptions	3 weeks

GreenbergPCoxCLeBeauMMInternational scoring system for evaluating prognosis in myelodysplastic syndromesBlood1997892079889058730

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ListAKurtinSRoeDJEfficacy of lenalidomide in myelodysplastic syndromesN Engl J Med20053525495715703420

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RazaAListABennettJLenalidomide (CC5013)-induced red blood cell (RBC) transfusion-independence (TI) responses in low-/int-1 risk patients with myelodysplastic syndromes (MDS): results of the multicenter mds 002 studyLeukemia research200529suppl1S70

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ListADewaldGBennettJLenalidomide in the myelodysplastic syndrome with chromosome 5q deletionN Engl J Med200635514566517021321

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