Background
Methods
Study design and patients
Randomization and masking
Procedures
Outcomes
Statistical analysis
Role of the funding source
Results
Patient disposition
Efficacy
Spleen response
Overall survival
Safety
Ruxolitinib (n = 155) | |||||
---|---|---|---|---|---|
0– < 12 Months | 12– < 24 Months | 24– < 36 Months | 36– < 48 Months | ≥48 Months | |
Event,*n/N (%) | |||||
Fatigue | 43/148.5 (29.0) | 14/92.0 (15.2) | 10/65.5 (15.3) | 5/45.0 (11.1) | 7/21.0 (33.3) |
Diarrhea | 41/147.5 (27.8) | 6/89.0 (6.7) | 7/65.0 (10.8) | 5/46.5 (10.8) | 3/20.5 (14.6) |
Ecchymosis | 31/146.0 (21.2) | 10/96.0 (10.4) | 4/70.0 (5.7) | 1/55.0 (1.8) | 1/25.0 (4.0) |
Dyspnea | 28/146.0 (19.2) | 10/98.5 (10.2) | 2/70.0 (2.9) | 2/54.5 (3.7) | 3/25.0 (12.0) |
Dizziness | 26/144.0 (18.1) | 10/96.0 (10.4) | 2/66.5 (3.0) | 1/49.5 (2.0) | 1/21.5 (4.7) |
Pain in extremity | 26/144.5 (18.0) | 6/97.0 (6.2) | 3/71.0 (4.2) | 2/51.5 (3.9) | 1/21.5 (4.7) |
Peripheral edema | 26/145.5 (17.9) | 7/99.5 (7.0) | 8/75.0 (10.7) | 3/53.5 (5.6) | 2/23.0 (8.7) |
Headache | 24/144.5 (16.6) | 5/99.0 (5.1) | 3/75.0 (4.0) | 4/58.0 (6.9) | 4/26.0 (15.4) |
Nausea | 24/144.5 (16.6) | 7/102.5 (6.8) | 4/79.0 (5.1) | 5/61.0 (8.2) | 4/27.5 (14.5) |
Constipation | 21/145.0 (14.5) | 10/105.0 (9.5) | 8/78.5 (10.2) | 4/56.5 (7.1) | 4/25.0 (16.0) |
Abdominal pain | 20/144.5 (13.8) | 6/106.0 (5.7) | 3/84.0 (3.6) | 4/66.0 (6.1) | 4/29.5 (13.6) |
Insomnia | 20/144.5 (13.8) | 7/104.5 (6.7) | 3/80.0 (3.8) | 1/62.5 (1.6) | 1/28.0 (3.6) |
Vomiting | 20/145.5 (13.7) | 3/105.5 (2.8) | 2/82.5 (2.4) | 4/64.5 (6.2) | 4/29.0 (13.8) |
Pyrexia | 20/148.0 (13.5) | 8/109.5 (7.3) | 7/82.5 (8.5) | 3/62.0 (4.8) | 2/27.5 (7.3) |
Cough | 19/145.0 (13.1) | 14/105.5 (13.3) | 3/74.5 (4.0) | 4/58.5 (6.8) | 4/26.0 (15.4) |
Arthralgia | 17/144.0 (11.8) | 6/103.0 (5.8) | 6/75.5 (7.9) | 6/53.5 (11.2) | 3/21.5 (14.0) |
Muscle spasms | 14/143.0 (9.8) | 3/105.0 (2.9) | 7/81.0 (8.6) | 6/58.0 (10.3) | 1/23.0 (4.3) |
Back pain | 13/143.0 (9.1) | 11/106.5 (10.3) | 0 | 4/58.0 (6.9) | 3/25.5 (11.8) |
Night sweats | 13/143.0 (9.1) | 3/105.5 (2.8) | 3/81.5 (3.7) | 1/61.5 (1.6) | 4/28.0 (14.3) |
Pneumonia | 13/145.0 (9.0) | 7/110.0 (6.4) | 3/82.5 (3.6) | 3/65.0 (4.6) | 5/30.5 (16.4) |
Upper respiratory tract infection | 11/143.0 (7.7) | 12/108.0 (11.1) | 4/74.5 (5.4) | 4/55.0 (7.3) | 3/24.0 (12.5) |
Fall | 7/143.5 (4.9) | 2/111.5 (1.8) | 1/87.0 (1.1) | 3/68.5 (4.4) | 4/30.5 (13.1) |
Musculoskeletal pain | 7/143.0 (4.9) | 5/112.0 (4.5) | 7/85.5 (8.2) | 2/62.5 (3.2) | 4/29.0 (13.8) |
Pruritus | 7/142.5 (4.9) | 8/110.5 (7.2) | 1/81.0 (1.2) | 1/63.5 (1.6) | 3/29.0 (10.3) |
Herpes zoster | 3/143.5 (2.1) | 4/115.5 (3.5) | 3/87.5 (3.4) | 3/66.0 (4.5) | 3/29.0 (10.3) |
Squamous cell carcinoma | 0 | 1/116.5 (0.9) | 2/91.5 (2.2) | 2/70.5 (2.8) | 4/32.0 (12.5) |
Ruxolitinib (n = 155) | |||||
---|---|---|---|---|---|
0– < 12 Months | 12– < 24 Months | 24– < 36 Months | 36– < 48 Months | ≥48 Months | |
Event,*n/N (%) | |||||
Fatigue | 9/144.5 (6.2) | 1/113.0 (0.9) | 3/90.0 (3.3) | 1/69.5 (1.4) | 0 |
Pneumonia | 8/144.0 (5.6) | 4/112.0 (3.6) | 3/86.0 (3.5) | 2/67.5 (3.0) | 5/32.0 (15.6) |
Abdominal pain | 6/143.5 (4.2) | 0 | 3/93.5 (3.2) | 1/72.5 (1.4) | 1/32.0 (3.1) |
Arthralgia | 3/142.5 (2.1) | 0 | 0 | 1/70.0 (1.4) | 0 |
Diarrhea | 3/143.5 (2.1) | 0 | 0 | 1/72.5 (1.4) | 0 |
Dyspnea | 3/143.5 (2.1) | 1/116.5 (0.9) | 2/92.5 (2.2) | 1/71.5 (1.4) | 1/31.5 (3.2) |
Pain in extremity | 3/142.5 (2.1) | 0 | 1/89.5 (1.1) | 1/69.5 (1.4) | 1/30.5 (3.3) |
Acute myeloid leukemia | 2/143.5 (1.4) | 0 | 1/93.0 (1.1) | 2/74.0 (2.7) | 0 |
Fall | 2/142.5 (1.4) | 1/114.5 (0.9) | 0 | 2/71.0 (2.8) | 1/30.5 (3.3) |
Gastrointestinal hemorrhage | 2/142.5 (1.4) | 1/115.0 (0.9) | 0 | 0 | 0 |
Hyperuricemia | 2/142.5 (1.4) | 1/114.5 (0.9) | 0 | 1/71.5 (1.4) | 0 |
Hypoxia | 2/142.5 (1.4) | 0 | 2/92.0 (2.2) | 0 | 1/31.5 (3.2) |
Muscular weakness | 2/143.0 (1.4) | 0 | 1/91.5 (1.1) | 0 | 0 |
Septic shock | 2/143.5 (1.4) | 0 | 0 | 0 | 0 |
Acute renal failure | 1/142.5 (0.7) | 1/116.0 (0.9) | 3/93.0 (3.2) | 2/72.5 (2.8) | 1/31.5 (3.2) |
Back pain | 1/142.5 (0.7) | 2/116.0 (1.7) | 0 | 0 | 0 |
Congestive cardiac failure | 1/142.5 (0.7) | 0 | 1/92.0 (1.1) | 0 | 2/32.5 (6.2) |
Epistaxis | 1/143.0 (0.7) | 2/117.0 (1.7) | 0 | 0 | 0 |
Sepsis | 1/143.0 (0.7) | 2/116.5 (1.7) | 2/92.5 (2.2) | 1/73.0 (1.4) | 2/32.5 (6.2) |
Upper abdominal pain | 1/143.0 (0.7) | 0 | 2/92.5 (2.2) | 0 | 0 |
Cellulitis | 0 | 0 | 0 | 2/73.5 (2.7) | 0 |
Myocardial infarction | 0 | 1/117.0 (0.9) | 0 | 2/73.5 (2.7) | 0 |
Osteoarthritis | 0 | 0 | 1/92.5 (1.1) | 0 | 2/32.5 (6.2) |
Osteomyelitis | 0 | 0 | 0 | 2/73.0 (2.7) | 0 |
Squamous cell carcinoma | 0 | 1/116.5 (0.9) | 0 | 0 | 2/32.5 (6.2) |
Urinary tract infection | 0 | 1/116.5 (0.9) | 1/92.0 (1.1) | 0 | 2/33.0 (6.1) |
Wound infection | 0 | 0 | 0 | 0 | 2/33.0 (6.1) |
Median duration of exposure, d | Ruxolitinib randomized (n = 155) | Ruxolitinib crossover (n = 111)* | During placebo treatment (n = 151)* | |||
---|---|---|---|---|---|---|
1045.0 | 777.0 | 260.0 | ||||
All grade | Grade 3 or 4 | All grade | Grade 3 or 4 | All grade | Grade 3 or 4 | |
Event, n/PYE (rate per 100 PYE) | ||||||
Infections and infestationsa
| ||||||
Upper respiratory tract infection | 34/398.0 (8.5) | 0 | 22/230.5 (9.5) | 0 | 15/96.9 (15.5) | 1/96.9 (1.0) |
Urinary tract infection | 31/414.3 (7.5) | 4/414.3 (1.0) | 16/240.5 (6.7) | 3/240.5 (1.2) | 7/101.3 (6.9) | 1/101.3 (1.0) |
Pneumonia | 31/432.3 (7.2) | 22/432.3 (5.1) | 18/253.6 (7.1) | 8/253.6 (3.2) | 11/102.4 (10.7) | 8/102.4 (7.8) |
Herpes zoster | 16/452.5 (3.5) | 0 | 14/241.2 (5.8) | 1/242.2 (0.4) | 1/104.1 (1.0) | 0 |
Bronchitis | 14/450.5 (3.1) | 0 | 11/244.9 (4.5) | 3/244.9 (1.2) | 2/104.2 (1.9) | 0 |
Nasopharyngitis | 14/449.1 (3.1) | 0 | 9/253.6 (3.5) | 0 | 9/98.4 (9.1) | 0 |
Sinusitis | 12/453.2 (2.6) | 1/453.2 (0.2) | 7/252.3 (2.8) | 0 | 3/102.7 (2.9) | 1/102.7 (1.0) |
Cellulitis | 10/467.8 (2.1) | 2/467.8 (0.4) | 3/262.6 (1.1) | 0 | 2/103.5 (1.9) | 0 |
Influenza | 8/469.0 (1.7) | 0 | 3/266.0 (1.1) | 1/266.0 (0.4) | 0 | 0 |
Sepsis | 8/480.3 (1.7) | 8/480.3 (1.7) | 4/267.4 (1.5) | 4/267.4 (1.5) | 2/104.0 (1.9) | 1/104.0 (1.0) |
Tooth abscess | 7/476.3 (1.5) | 1/476.3 (0.2) | 4/261.3 (1.5) | 0 | 0 | 0 |
Oral herpes | 6/469.8 (1.3) | 0 | 2/269.1 (0.7) | 0 | 2/103.2 (1.9) | 0 |
Skin infection | 5/469.8 (1.1) | 0 | 3/269.5 (1.1) | 0 | 1/104.4 (1.0) | 0 |
Viral infection | 5/471.2 (1.1) | 0 | 2/265.4 (0.8) | 0 | 0 | 0 |
Viral gastroenteritis | 4/470.6 (0.9) | 0 | 1/270.1 (0.4) | 0 | 2/103.5 (1.9) | 0 |
Diverticulitis | 4/475.0 (0.8) | 1/475.0 (0.2) | 3/268.5 (1.1) | 1/268.5 (0.4) | 2/103.6 (1.9) | 0 |
Ear infection | 4/473.3 (0.8) | 0 | 4/267.8 (1.5) | 0 | 0 | 0 |
Fungal infection | 4/479.4 (0.8) | 0 | 2/267.6 (0.7) | 1/267.6 (0.4) | 2/103.8 (1.9) | 0 |
Localized infection | 4/479.1 (0.8) | 0 | 1/269.2 (0.4) | 1/269.2 (0.4) | 1/104.1 (1.0) | 0 |
Lower respiratory tract infection | 4/476.9 (0.8) | 0 | 1/270.5 (0.4) | 0 | 2/103.3 (1.9) | 1/103.3 (1.0) |
Septic shock | 2/484.6 (0.4) | 2/484.6 (0.4) | 3/270.5 (1.1) | 3/270.5 (1.1) | 0 | 0 |
Neoplasms | ||||||
Basal cell carcinoma | 12/450.9 (2.7) | 2/450.9 (0.4) | 10/252.7 (4.0) | 2/252.7 (0.8) | 4/103.7 (3.9) | 0 |
Squamous cell carcinoma | 10/462.6 (2.2) | 2/462.6 (0.8) | 10/252.0 (4.0) | 3/252.0 (1.2) | 4/102.9 (3.9) | 0 |
Squamous cell carcinoma of the skin | 9/470.2 (1.9) | 3/470.2 (0.6) | 3/266.4 (1.1) | 1/266.4 (0.4) | 1/104.7 (1.0) | 0 |
Acute myeloid leukemia | 5/483.8 (1.0) | 5/483.8 (1.0) | 5/270.1 (1.9) | 5/270.1 (1.9) | 0 | 0 |
Cause of death, n (%)a
| Ruxolitinib randomized (n = 155) | After ruxolitinib crossoverb (n = 111) | During placebo treatment (n = 151) |
---|---|---|---|
Death caused by any treatment-emergent adverse event | 28 (18.1) | 28 (25.2) | 11 (7.3) |
Sepsis | 4 (2.6) | 2 (1.8) | 1 (0.7) |
Disease progression | 3 (1.9) | 4 (3.6) | 3 (2.0) |
Pneumonia | 3 (1.9) | 1 (0.9) | 1 (0.7) |
Acute myeloid leukemia | 2 (1.3) | 3 (2.7) | 0 |
Cerebral hemorrhage | 2 (1.3) | 1 (0.9) | 1 (0.7) |
Septic shock | 2 (1.3) | 2 (1.8) | 0 |
Acute renal failure | 1 (0.6) | 1 (0.9) | 0 |
Anemia | 1 (0.6) | 0 | 0 |
Cardiac arrest | 1 (0.6) | 0 | 0 |
Death, unspecified | 1 (0.6) | 1 (0.9) | 0 |
Falling injury | 1 (0.6) | 0 | 0 |
Hemorrhagic shock | 1 (0.6) | 1 (0.9) | 0 |
Metastatic NSCLC | 1 (0.6) | 0 | 0 |
Multiorgan failure | 1 (0.6) | 0 | 1 (0.7) |
Muscular weakness | 1 (0.6) | 0 | 0 |
Myocardial infarction | 1 (0.6) | 1 (0.9) | 0 |
Pancreatic carcinoma | 1 (0.6) | 0 | 0 |
Renal failure | 1 (0.6) | 0 | 0 |
Respiratory failure | 1 (0.6) | 0 | 0 |
Splenic infarction | 1 (0.6) | 0 | 0 |
Congestive cardiac failure | 0 | 2 (1.8) | 0 |
Myelofibrosis | 0 | 2 (1.8) | 1 (0.7) |
Cardiac failure | 0 | 1 (0.9) | 0 |
Pneumonia aspiration | 0 | 2 (1.8) | 0 |
Anastomotic hemorrhage | 0 | 1 (0.9) | 0 |
Cholecystitis | 0 | 1 (0.9) | 0 |
Delirium | 0 | 1 (0.9) | 0 |
Road traffic accident | 0 | 1 (0.9) | 0 |
Splenic rupture | 0 | 1 (0.9) | 0 |
Suicide | 0 | 1 (0.9) | 0 |
Gastrointestinal hemorrhage | 0 | 0 | 1 (0.7) |
Intestinal perforation | 0 | 0 | 1 (0.7) |
Staphylococcal infection | 0 | 0 | 1 (0.7) |