TABLE 4.
R1 Steroid Morbidity and Mortality and Selected Toxicities by R2 Arm
| Event | Standard (n = 950), No. (%) | Short (n = 952), No. (%) | P |
|---|---|---|---|
| R1 random assignment | |||
| Serious steroid AEa | 107 | 97 | |
| Grade 3+ dex-related SAE | 203 | 194 | |
| Induction TRM | 6 | 10 | |
| Any event | 242 (25.5) | 227 (23.8) | .41 |
| Blood and lymphatic system disorders | 19 (2.0) | 43 (4.5) | |
| Cardiac disorders | 4 (0.4) | 0 | |
| GI disorders | 36 (3.8) | 37 (3.9) | |
| General disorders and administration site conditions | 11 (1.2) | 5 (0.5) | |
| Hepatobiliary disorders | 3 (0.3) | 0 | |
| Infections and infestations | 128 (13.5) | 115 (12.1) | |
| Injury, poisoning, and procedural complications | 1 (0.1) | 2 (0.2) | |
| Investigations | 12 (1.3) | 4 (0.4) | |
| Metabolism and nutrition disorders | 20 (2.1) | 20 (2.1) | |
| Musculoskeletal and connective tissue disorders | 9 (1.0) | 1 (0.1) | |
| Nervous system disorders | 19 (2.0) | 10 (1.1) | |
| Psychiatric disorders | 4 (0.4) | 0 | |
| Renal and urinary disorders | 5 (0.5) | 1 (0.1) | |
| Respiratory, thoracic, and mediastinal disorders | 3 (0.3) | 5 (0.5) | |
| Skin and subcutaneous tissue disorders | 1 (0.1) | 1 (0.1) | |
| Vascular disorders | 28 (2.9) | 13 (1.4) |
| Event | SIM (n = 778), No. (%) | HDM (n = 742), No. (%) | P |
|---|---|---|---|
| R2 IM random assignment | |||
| Fatal AE | 0 | 0 | |
| Life-threatening or resulted in permeant disability of deathb | 8 (1.0) | 10 (1.3) | .56 |
| Any grade 3+ AE | 426 (54.8) | 392 (52.8) | .47 |
| Renal and urinary disorders | 1 (0.1) | 17 (2.3) | .0001 |
| Acute kidney injury | 1 (0.1) | 13 (1.8) | .0007 |
| Pancreatitis | 0 | 6 (0.8) | .013 |
| Creatinine increased | 0 | 5 (0.7) | .028 |
| Blood and lymphatic system disorders | 177 (22.8) | 136 (18.3) | .036 |
| WBC decreased | 119 (15.3) | 87 (11.7) | .043 |
| Event | Pulses (n = 769) | No Pulses (n = 739) | P |
|---|---|---|---|
| R2 Pulses Random Assignment | |||
| Stopped early due to AEs, No. (%) | 9 (1.2) | 7 (1.0) | .80 |
| Any SAE, No. (%) | 442 (57.5) | 411 (55.6) | .47 |
| Fatal SAE, No. (%)c | 1 (0.1) | 1 (0.1) | .98 |
| Life-threatening or resulted in permeant disability of death,d No. (%) | 28 (3.6) | 31 (4.2) | .58 |
| Number of SAEs, median (IQR) | 1 (0-2) | 1 (0-2) | .30 |
| Range | 0-20 | 0-15 | |
| Nonfatal AEs grade 3-4 | N = 768 | N = 739 | |
| Any nonfatal AEs, N (%) | 686 (89.3) | 619 (83.8) | .0019 |
| Number of AEs, median (IQR) | 10 (4-22) | 8 (2-18) | <.0001 |
| Febrile neutropenia, No. (%) | 460 (59.9) | 367 (49.7) | .0001 |
| Median (IQR) | 1 (0-2) | 0 (0-1) | <.0001 |
| ALT increased, No. (%) | 161 (21.0) | 104 (14.1) | .0005 |
| Hyperglycemia, No. (%) | 11 (1.4) | 1 (0.1) | .0063 |
| Platelet count decreased, No. (%) | 66 (8.6) | 97 (13.1) | .0048 |
| Psychiatric disorders, No. (%) | 27 (3.5) | 8 (1.1) | .0018 |
| Pain in extremity, No. (%) | 8 (1.0) | 0 | .0077 |
| AST increased, No. (%) | 22 (2.9) | 5 (0.7) | .0015 |
| Creatinine increased, No. (%) | 8 (1.0) | 0 | .0077 |
Abbreviations: AE, adverse event; CMV, cytomegalovirus; dex, dexamethasone; HDM, high-dose methotrexate; HLH, hemophagocytic lymphohistiocytosis; IM, interim maintenance; R1, randomization 1; R2, randomization 2; SAE, serious AE; SIM, standard interim maintenance; TRM, treatment-related mortality.
Serious, grade 3 or AEs related to induction and categorized as steroid-related or steroid-contributory.
SIM arm: anaphylaxis (n = 2), toxic epidermal necrolysis (n = 1), spinal fracture (n = 1), peripheral motor neuropathy (n = 1), febrile neutropenia (n = 1), weight loss (n = 1), and seizure (n = 1); HDM arm: pancreatitis (n = 1), avascular necrosis (n = 1), seizure (n = 2), allergic reaction (n = 1), sepsis (n = 1), anaphylaxis (n = 1), hemiplegia (n = 1), and encephalopathy (n = 1).
Pulse arm: CMV pneumonitis (n = 1); no pulse arm: intraoperative splenic injury (n = 1).
Pulses arm (one patient had two events): avascular necrosis (n = 10), bronchospasm (n = 1), depressed level of consciousness (n = 1), febrile neutropenia (n = 2), fracture (n = 2), headache (n = 1), lethargy (n = 1), lung infection (n = 1), mucosal infection (n = 1), seizure (n = 1), sepsis (n = 3), upper respiratory infection (n = 1), wrist fracture (n = 1), HLH (n = 1), CMV pneumonitis (n = 1), and fungal infection/pneumonia (n = 1). No pulse arm (one patient had five events and one had 2): anaphylaxis (n = 1), osteonecrosis (n = 7), depressed level of consciousness (n = 1), febrile neutropenia (n = 1), fever (n = 2), fracture (n = 2), hypoglycemia (n = 1), hypoxia (n = 1), intracranial hemorrhage (n = 1), intraoperative splenic injury (n = 1), lung infection (n = 1), pneumothorax (n = 1), respiratory failure (n = 1), seizure (n = 5), sepsis (n = 7), stridor (n = 2), tracheal obstruction (n = 1), and tracheitis (n = 1).