The following adverse reactions are also discussed in other sections of the labeling:
- For intravenous use only [see WARNINGS AND PRECAUTIONS]
- Extravasation tissue injury [see WARNINGS AND PRECAUTIONS]
- Peripheral Neuropathy [see WARNINGS AND PRECAUTIONS]
- Myelosuppression [see WARNINGS AND PRECAUTIONS]
- Tumor lysis syndrome [see WARNINGS AND PRECAUTIONS]
- Constipation and bowel obstruction [see WARNINGS AND PRECAUTIONS]
- Fatigue [see WARNINGS AND PRECAUTIONS]
- Hepatic toxicity [see WARNINGS AND PRECAUTIONS]
Clinical Trials Safety Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Integrated Summary of Safety in Relapsed and/or Refractory Ph- Adult Acute Lymphoblastic Leukemia
Marqibo, at a dose of 2.25 mg/m² weekly, was studied in a total of 83 patients in two trials: study 1 and study 2. Adverse reactions were observed in 100% of patients. The most common adverse reactions ( > 30%) were constipation (57%), nausea (52%), pyrexia (43%), fatigue (41%), peripheral neuropathy (39%), febrile neutropenia (38%), diarrhea (37%), anemia (34%), decreased appetite (33%), and insomnia (32%).
Adverse reactions of Grade 3 or greater were reported in 96% of patients. Adverse reactions of Grade 3 or greater and occurring in ≥ 5% of patients are summarized in Table 2.
Table 2: Most Commonly Reported ( > 5%) Gradea 3 or Greater Adverse Reactions among 83 Patients Receiving the Clinical Dosing Regimen
|Adverse Reactions Grade ≥ 3||Study 1 and 2
|Blood and Lymphatic System Disorders||47 (56.6)|
|Febrile Neutropenia||26 (31.3)|
|Septic Shock||5 (6.0)|
|Staphylococcal Bacteremia||5 (6.0)|
|Peripheral Sensory and Motor Neuropathy||14 (16.7)|
|Ileus, Colonic Pseudo-Obstruction||5 (6.0)|
|Muscular Weakness||1 (1.2)|
|Respiratory Thoracic and Mediastinal Disorders||17 (20.5)|
|Respiratory Distress||5 (6.0)|
|Respiratory Failure||4 (4.8)|
|General Disorders and Administration Site Condition||31 (37.3)|
|Gastrointestinal Disorders||21 (25.3)|
|Abdominal Pain||7 (8.4)|
|Aspartate Aminotransferase Increased||6 (7.2)|
|Vascular Disorders||8 (9.6)|
|Psychiatric Disorders||9 (10.8)|
|Mental Status Changes||3 (3.6)|
|Cardiac Disorders||9 (10.8)|
|Cardiac Arrest||5 (6.0)|
|Renal and Urinary Disorders||6 (7.2)|
|Musculoskeletal and Connective Tissue Disorders||7 (8.4)|
|a National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0.
bIncluding neuropathy-associated adverse reactions.
A total of 75.9% of patients experienced serious adverse events (SAEs) during the studies. The most commonly reported SAEs included febrile neutropenia (20.5%), pyrexia (13.3%), hypotension (7.2%), respiratory distress (6.0%), and cardiac arrest (6.0%).
Dose reduction, delay, or omission occurred in 53% of patients during the treatment.
Twenty-eight percent of patients experienced adverse reactions leading to treatment discontinuation. The most common adverse reactions that caused treatment discontinuation were peripheral neuropathy (10%), leukemia-related (7%), and tumor lysis syndrome (2%).
Adverse reactions related to neuropathy and leading to treatment discontinuation were decreased vibratory sense, facial palsy, hyporeflexia, constipation, asthenia, fatigue, and musculoskeletal pain, each reported in at least 1 patient.
Deaths occurred in 23% of patients in study 1. The non-leukemia related causes of deaths were brain infarct (1), intracerebral hemorrhage (2), liver failure (1), multi system organ failure (2), pneumonia and septic shock (3), respiratory failure (4), pulmonary hemorrhage (1), and sudden cardiac death (1).