Treatment and management of myelofibrosis in the era of JAK inhibitors

Figures & data

Table 1 Prognostic risk assessment

Variable	IPSS	DIPSS	DIPSS plusa
Age >65 years	✓	✓
Constitutional symptoms	✓	✓
Hemoglobin <10 g/dL	✓	✓✓
Leukocyte count >25 × 10^9/L	✓	✓
Circulating blasts ≥1%	✓	✓
Platelet count <100 × 10^9/L			✓
RBC transfusion need			✓
Unfavorable karyotype:			✓
+8, −7/7q−, isochromosome (17q),
inversion (3), deletion −5/5q−,
12p−, 11q23 rearrangement

Notes: ✓ = 1 point each.

a For DIPSS plus, the score is derived from the DIPSS score and additional points added as per the table.

Abbreviations: IPSS, international Prognostic Scoring System; DIPSS, dynamic IPSS; RBC, red blood cell.

Table 2 Hematologic laboratory abnormalities

Laboratory parameter	COMFORT-I^Citation17				COMFORT-II^Citation18
	Ruxolitinib (N = 155)		Placebo (N = 151)		Ruxolitinib (N = 146)		BAT (N = 73)
	All grades, %	Grade ≥3, %	All grades, %	Grade ≥3, %	All grades, %	Grade ≥3, %	All grades, %	Grade ≥3, %
Anemia	83	45	44	16	82	40	49	21
Thrombocytopenia	71	14	21	2	69	9	29	7
Neutropenia	19	7	4	3	12	6	8	1

Note: Reproduced with permission from Novartis Pharmaceuticals Canada Inc. Jakavi (ruxolitinib) [product monograph]. Dorval, QC: 2012.⁵⁸

Abbreviations: BAT, best available therapy; COMFORT, COntrolled MyeloFibrosis Study With ORal JAK Inhibitor Treatment.

Figure 1 Kaplan–Meier analysis of overall survival in (A) COMFORT-I²¹ and (B) COMFORT-II²⁰ with 24 months of follow-up.

Republished with permission of American Society of Hematology; High Wire Press, from A comprehensive review and analysis of the effect of ruxolitinib therapy on the survival of patients with myelofibrosis. Mascarenhas J, Hoffman R. Blood. 121(24):2013; permission conveyed through Copyright Clearance Center, Inc.⁵⁹

Note: ^aP-values and CIs are unadjusted for repeat analyses.
Abbreviations: CI, confidence interval; HR, hazard ratio; BAT, best available therapy; COMFORT, COntrolled MyeloFibrosis Study With ORal JAK Inhibitor Treatment.

Table 3 Ruxolitinib combination therapy – clinical studies

Combination agent	Study title	Trial identifier
Lenalidomide	Ruxolitinib and Lenalidomide for Patients with Myelofibrosis	NCT01375140
Pomalidomide	Ruxolitinib and Pomalidomide Combination Therapy in Patients with Primary and Secondary MF (POMINC)	NCT01644110
Danazol	Ruxolitinib Phosphate and Danazol in Treating Anemia in Patients with Myelofibrosis	NCT01732445
Panobinostat	Panobinostat and Ruxolitinib in Myelofibrosis (PRIME Trial)	NCT01693601
Buparlisib (BKM120)	A Study to Find the Maximum Tolerated Dose of the Experimental Combination of the Drugs INC424 and BKM120 in Patients with Primary or Secondary Myelofibrosis	NCT01730248
LDE225	A Phase Ib/II Dose-finding Study to Assess the Safety and Efficacy of LDE225 + INC424 in Patients with MF	NCT01787552
Stem cell transplantation	Ruxolitinib Prior to Transplant in Patients with Myelofibrosis	NCT01790295

Abbreviation: MF, myelofibrosis.

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