Analysis of predictors of response to ruxolitinib in patients with myelofibrosis in the phase 3b expanded-access JUMP study

Figures & data

Figure 1. Study design. ^aIncluded by amendment to the protocol. ^bPatients were treated for up to 24 months after the last patient’s first visit (December 23, 2014), unless discontinuation criteria were met. BID: twice daily; Int: intermediate; PET-MF: post-essential thrombocythemia myelofibrosis; PLT: platelet; PMF: primary myelofibrosis: PPV-MF: post-polycythemia vera myelofibrosis.

Table 1. Patient baseline characteristics.

Characteristic	N = 2233
Age, median (range), years	67.0 (18–89)
≥65 years, n (%)	1334 (59.7)
Male, n (%)	1217 (54.5)
Time since initial diagnosis, mean (SD), months	51.7 (64.4)
n	2229
>2 years, n (%)	1152 (51.6)
≤2 years, n (%)	1081 (48.4)
MF subtype, n (%)
Primary	1326 (59.4)
Secondary	906 (40.6)
Missing	1 (<0.1)
IPSS risk, n (%)^a
Low/intermediate-1	365 (16.3)
Intermediate-2/high	772 (34.6)
Missing	1096 (49.1)
DIPSS risk, n (%)^b
Low/intermediate-1	895 (40.1)
Intermediate-2	755 (33.8)
High	194 (8.7)
Missing	389 (17.4)
Hb level, mean (SD), g/dL	10.9 (2.3)
n	2226
<10 g/dL, n (%)	856 (38.5)
≥10 g/dL, n (%)	1370 (61.5)
Platelet count, mean (SD), × 10^9/L	318.9 (238.6)
n	2225
<100 × 10^9/L, n (%)	138 (6.2)
≥100 × 10^9/L, n (%)	2087 (93.8)
Missing, n (%)	8 (0.4)
WBC count, mean (SD), × 10^9/L	16.4 (16.05)
n	2223
≤25 × 10^9/L, n (%)	1827 (81.2)
>25 × 10^9/L, n (%)	396 (17.8)
Missing, n (%)	10 (0.4)
Treatment history, n (%)
Treatment-naive	909 (40.7)
Prior treatment	1324 (59.3)
Prior transfusions	578 (25.9)
Transfusion-dependent, n (%)^c	158 (7.1)
Transfusion-independent, n (%)	2075 (92.9)
Peripheral blasts ≥1%, n (%) (n = 2025)	713 (31.9)
Palpable spleen length, median (range), cm	12.0 (0.5–45.0)
n	2079
≥10 cm, n (%)	1472 (65.9)
<10 cm, n (%)	761 (34.1)

DIPSS: Dynamic International Prognostic Scoring System; Hb: hemoglobin; IPSS: International Prognostic Scoring System; MF: myelofibrosis; SD: standard deviation; WBC: white blood cell.

^aIPSS risk data were collected following a protocol amendment (amendment 2, September 2012).

^bDIPSS risk was calculated based on available patient data.

^cTransfusion-dependence was defined as having received ≥ 6 transfusion units over the 12-week period prior to starting treatment with ruxolitinib.

Table 2. Comparison of baseline Hb levels and platelet counts with ruxolitinib dose at Week 12.

Subgroup	Hematologic parameters at baseline	Evaluable patients, n	Total daily dose of ruxolitinib >20 mg/day at Week 12, n (%)	Total daily dose of ruxolitinib ≤20 mg/day at Week 12, n (%)
1	Hb level >10 g/dL and platelet count >100 × 10^9/L	1162	781 (67.2)	381 (32.8)
2	Either Hb level <10 g/dL or platelet count <100 × 10^9/L	813	456 (56.1)	357 (43.9)
3	Both Hb level <10 g/dL and platelet count <100 × 10^9/L	60	3 (5.0)	57 (95.0)

Hb: hemoglobin.

Figure 2. Factors predicting higher spleen response rates in multivariate analysis. ORs and the corresponding 95% CIs were derived by fitting a logistic regression with response as a binomial independent variable and the patient subgroups as binomial covariates. Factors associated with a higher spleen response rate are shown in bold font. Patient characteristics favored by the OR are labeled with a dot (•). BL: baseline; CI: confidence interval; DIPSS: Dynamic International Prognostic Scoring System; IPSS: International Prognostic Scoring System; LCM: left costal margin; MF: myelofibrosis; OR: odds ratio; WBC: white blood cell.

Figure 3. Factors predicting improvements in HRQoL and symptoms, assessed by improvements in FACT–Lym total score (A) and FACIT-F score (B) in multivariate analyses. ORs and the corresponding 95% CIs were derived by fitting a logistic regression with response as a binomial independent variable and the patient subgroups as binomial covariates. Factors associated with a higher spleen response rate are shown in bold font. Patient characteristics favored by the OR are labeled with a dot (•). BL: baseline; CI: confidence interval; DIPSS: Dynamic International Prognostic Scoring System; FACT-Lym: Functional Assessment of Cancer Therapy-Lymphoma; FACIT-F: Functional Assessment of Chronic Illness Therapy-Fatigue; HRQoL: health-related quality of life; IPSS: International Prognostic Scoring System; LCM: left costal margin; MF: myelofibrosis; OR: odds ratio; WBC: white blood cell.

Figure 4. Kaplan–Meier estimate of overall survival of spleen responders vs non-responders at Week 24 stratified by DIPSS risk status. Spleen response was defined as having a non-palpable spleen at Week 24 (in patients with a palpable spleen 5–10 cm below the left costal margin at baseline) or a decrease in spleen length by ≥50% at Week 24 (in patients with a palpable spleen >10 cm at baseline). Patients with missing spleen data were considered non-responders. CI: confidence interval; DIPSS: Dynamic International Prognostic Scoring System; Int: intermediate; NE: not evaluable.

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