Patient characteristics and outcomes after ruxolitinib discontinuation in patients with myelofibrosis

Figures & data

Figure 1. Cohort selection. Abbreviations. PMF, Primary Myelofibrosis; sMF, Secondary Myelofibrosis; PV, Polycythemia Vera; ET, Essential Thrombocythemia; SM, SEER Medicare; TR, Truven; OP, Optum.

Table 1. Baseline characteristics.

	Cohort with ruxolitinib discontinuation, (N = 290)
Age, years
Mean (SD)	69.0 (10.2)
Median (IQR)	68.0 (62.0−77.0)
Minimum, Maximum	39, 93
Age at ruxolitinib discontinuation, years, n (%)
<45−64	113 (39)
65−74	83 (29)
75−84	77 (27)
≥85	17 (6)
Gender, n (%)
Male	145 (50)
Number of prior LOTs
Mean (SD)	0.9 (1.1)
Median (IQR)	1.0 (0–1.0)
Minimum, Maximum	0, 6
Number of days from ruxolitinib initiation date to discontinuation date
Mean (SD)	372 (299.0)
Median (IQR)	284 (113.0−562.0)
Minimum, Maximum	0, 1225
Number of days from ruxolitinib discontinuation date to end of follow-up
Mean (SD)	167.8 (213.9)
Median (IQR)	70.9 (6.9−251.8)
Minimum, Maximum	0, 979
Post ruxolitinib regimens containing, n (%)
Erythropoietin, Hydroxyurea	20 (6.89)
Others*	29 (10.00)
None of the above	241 (83.10)

Note: Patients exposed to ruxolitinib after index MF diagnosis were included in this table. Ruxolitinib discontinuation date is defined as the last date on which a patient was exposed to ruxolitinib.

Percentages are based on N within the column header.

Abbreviations. SD, Standard deviation; LOTs, Line of treatments; MF, Myelofibrosis.

Regimens defined as *Others include radiation, best supportive care, steroids only, hormones, immunomodulatory drugs (e.g. lenalidomide and thalidomide).

Table 2. Treatment emergent morbidities and transfusions.

Event	Timepoint of assessment
	Following ruxolitinib initiation (baseline) (N = 290)				Prior to ruxolitinib discontinuation* (N = 290)				After ruxolitinib discontinuation^† (N = 163)
	30 Days	60 Days	90 Days	180 Days	30 Days	60 Days	90 Days	180 Days	30 Days	60 Days	90 Days	180 Days
Diagnosis of AML, n (%)**				15 (5)	12 (4)	13 (4)	14 (5)	17 (6)	12 (7)	14 (9)	16 (10)	19 (12)
Diagnosis of anemia, n (%)	105 (36)	153 (53)	174 (60)	191 (66)	131 (45)	163 (56)	183 (63)	203 (70)	86 (53)	106 (65)	112 (69)	125 (77)
Diagnosis of thrombocytopenia, n (%)	31 (11)	53 (18)	66 (23)	84 (29)	51 (18)	70 (24)	83 (29)	100 (34)	38 (23)	54 (33)	58 (36)	69 (42)
Diagnosis of neutropenia, n (%)**			12 (4)	19 (7)		12 (4)	15 (5)	18 (6)	16 (10)	18 (11)	20 (12)	27 (17)
Diagnosis of RBC transfusion, n (%)	54 (19)	103 (36)	116 (40)	138 (48)	97 (33)	108 (37)	118 (41)	135 (47)	53 (33)	68 (42)	75 (46)	86 (53)

Note: Patients exposed to ruxolitinib after index MF diagnosis were included in this table. Ruxolitinib discontinuation date is defined as the last date on which a patient was exposed to ruxolitinib. Percentages are based on N within the column header.

**Values of 1–10 patients in any cell in this table have been suppressed to conform with CMS Cell Size Suppression Policy.

Abbreviations. AML, Acute Myeloid Leukemia; MF, Myelofibrosis; RBC, Red Blood Cells.

*This time point includes the date of ruxolitinib discontinuation.

^†This time point does not include date of ruxolitinib discontinuation. N is based on patients with 60 days of follow up after ruxolitinib discontinuation date.

Figure 2. Cumulative incidence of cytopenias in the presence of death as a competing event. The Y-axis is the cumulative probability of development of new cytopenia and the x-axis is time of first diagnosis of cytopenia. Cytopenias include anemia, neutropenia and thrombocytopenia.

Figure 3. OS, TPFS and TTNT of patients. Time to event analysis in the sample of myelofibrosis patients that discontinued ruxolitinib (n = 290). X-axis represents the event free probability and y-axis represents the follow-up time after ruxolitinib discontinuation. Event = death (Overall survival [OS] analysis), earlier of treatment progression/death (time to progression free survival [TPFS] analysis) and treatment progression (time to next treatment [TTNT] analysis).

Table 3. Time to event efficacy outcomes.

	Time to next treatment^∗	Treatment progression-free survival^†	Overall survival^‡
Summary of censored and event cases
Total number of patients assessed	290	290	290
Number of patients with an event	49	123	102
Proportion of patients with an event, (%)	16.90	42.40	35
Kaplan-Meier statistics, months
Median (95% CI)	NE (11.2, NE)	6.0 (4.4, 8.3)	11.1 (8.4–14.5)^∗∗
Mean (SE)	10.828 (0.563)	9.495 (0.922)	13.688 (0.970)
Quarterly rates, %
3 month rate	80.80	68.70	84
6 month rate	73.60	50.50	69
9 month rate	65.60	37.70	55
12 month rate	61.30	27.10	47
Predictors of time to event analysis, HR (CI)
Age at ruxolitinib discontinuation date (Reference, ≤65 years)	1.311 (0.696, 2.469)	2.071 (1.320, 3.248)	3.845 (2.118, 6.981)
Prior RBC transfusion (Reference, No RBC transfusion)	1.046 (0.545, 2.007)	0.910 (0.610, 1.356)	0.833 (0.527, 1.316)
Charlson comorbidity index score	1.111 (0.994, 1.242)	1.172 (1.093, 1.257)	1.248 (1.154, 1.349)
Gender (Reference, Female)	1.853 (1.007, 3.408)	1.620 (1.108, 2.369)	1.324 (0.864, 2.029)

Note: Erythropoietin, hydroxyurea, chemotherapy, radiation, best supportive care, steroids, hormones, immunomodulatory drugs (e.g. lenalidomide and thalidomide) were considered as progression therapies.

Comorbidities included for calculating Charlson Comorbidity Index score are myocardial infarction, congestive heart failure, peripheral vascular disease, cerebrovascular disease, dementia, chronic pulmonary disease, rheumatic disease, peptic ulcer disease, mild liver disease, diabetes without chronic complications, diabetes with chronic complications, hemiplegia or paraplegia, renal disease, any malignancy without metastasis, leukemia, lymphoma, moderate or severe liver disease, metastatic solid tumor, and acquired immunodeficiency syndrome (excluded a symptomatic infection).

Abbreviations. CI, Confidence interval; HR, hazard ratio; NR, Not Estimable; SE, standard error; RBC, Red blood cells.

*Patients observed with any of the treatments mentioned above were considered to have an event. The event date is the earliest date on which a patient received a progression therapy. Patients without an observed event were censored on enrollment end date.

^†Patients with an observed death or progression to any of the treatments mentioned above were considered to have an event. The event date is the earliest date on which a patient received a progression therapy. If a patient did not receive a progression therapy but died, then the event date is date of death. Patients without an observed event were censored on enrollment end date.

^‡Patients with an observed death were considered to have an event. Patients without an observed death were censored on 31DEC2014 in SEER Medicare data and last claim date in Optum and Truven studies.

**After excluding patients who developed AML on or 30 days before ruxolitinib discontinuation date, median overall survival was 10.68 (8.21–14.49) months.

Availability of data and material

The data and protocol of this study are not publicly available but are available upon contact with [email protected] on reasonable request.