An objective disease response was seen in up to 35% (25/71) of patients in 2 CTCL studies1
a95% confidence interval.
Response rates above are rounded to the nearest whole number.
CR=complete response; ORR=objective disease response; PR=partial response.
SERIOUS ADVERSE REACTIONS
Infections were the most common type of serious adverse event reported in both studies with 8 patients (8%) in Study 1 and 26 patients (31%) in Study 2 experiencing a serious infection
The first FDA-approved treatment for CTCL to evaluate a global tumor (composite) response in all of the following disease sites1,18
ISTODAX—for 2nd-line systemic therapy across
CTCL subtypes, including mycosis fungoides
and Sézary syndrome.1,2
A durable response was achieved with a median duration of response of 15 months (range: 1-20+a) and 11 months (range: 1-66+a)1
aDenotes censored value.
DOR=duration of response.
Responses were evaluated in an advanced-stage population with 71% of patients in Study 1 and 87% of patients in Study 2 at stage IIB or greater1
SERIOUS ADVERSE REACTIONS (cont’d)
Serious adverse reactions reported in >2% of patients in Study 1 were sepsis and pyrexia (3%)
In Study 2, serious adverse reactions in >2% of patients were fatigue (7%), supraventricular arrhythmia, central-line infection, neutropenia (6%), hypotension, hyperuricemia, edema (5%), ventricular arrhythmia, thrombocytopenia, nausea, leukopenia, dehydration, pyrexia, aspartate aminotransferase increased, sepsis, catheter-related infection, hypophosphatemia, and dyspnea (4%)
ISTODAX demonstrated a durable response
in a population that included all disease
stages (IA-IVB) in 2 clinical studies1
A median time to objective disease response was seen in 2 months in 2 CTCL studies1
Median time to complete response in Study 1 (N=96) and Study 2 (N=71)1
The median time to complete response was 4 months and 6 months in Study 1 (n=6) and Study 2 (n=4), respectively (range: 2-9 months)
SERIOUS ADVERSE REACTIONS (cont’d)
Most deaths were due to disease progression. In Study 1, there were two deaths due to cardiopulmonary failure and acute renal failure. In Study 2, there were six deaths due to infection (4), myocardial ischemia, and acute respiratory distress syndrome
Romidepsin (ISTODAX) has a category 2A
recommendation from the NCCN Guidelines®
for CTCL based on Study 1 and Study 2.10,18,19
Myelosuppression: ISTODAX® (romidepsin) for injection can cause thrombocytopenia, leukopenia (neutropenia and lymphopenia), and anemia; monitor blood counts regularly during treatment with ISTODAX; interrupt and/or modify the dose as necessary
Infections: Fatal and serious infections, including pneumonia, sepsis, and viral reactivation, including Epstein Barr and hepatitis B viruses, have been reported during and within 30 days after treatment with ISTODAX in clinical trials. The risk of life threatening infections may be greater in patients with a history of prior treatment with monoclonal antibodies directed against lymphocyte antigens and in patients with disease involvement of the bone marrow. Reactivation of Epstein Barr viral infection led to liver failure. Consider monitoring for reactivation and antiviral prophylaxis in patients with evidence of prior hepatitis B infection. Ganciclovir prophylaxis failed to prevent Epstein Barr viral reactivation in one case
Electrocardiographic (ECG) changes: ECG changes have been observed with ISTODAX. In patients with congenital long QT syndrome, patients with a history of significant cardiovascular disease, and patients taking anti-arrhythmic medicines or medicinal products that lead to significant QT prolongation, consider cardiovascular monitoring of ECGs at baseline and periodically during treatment. Confirm that potassium and magnesium levels are within the normal range before administration of ISTODAX
Tumor lysis syndrome (TLS): TLS has been reported during treatment with ISTODAX. Patients with advanced stage disease and/or high tumor burden are at greater risk and should be closely monitored and managed as appropriate
Embryo-fetal toxicity: ISTODAX may cause fetal harm when administered to a pregnant woman. Advise women of potential hazard to the fetus and to avoid pregnancy while receiving ISTODAX
Cutaneous T-Cell Lymphoma The most common Grade 3/4 adverse reactions (>5%) regardless of causality in Study 1 (N=102) were infections (11%) and asthenia/fatigue (8%), and in Study 2 (N=83) were lymphopenia (37%), infections (33%), neutropenia (27%), leukopenia (22%), anemia (16%), asthenia/fatigue (14%), thrombocytopenia (14%), hypophosphatemia (10%), vomiting (10%), dermatitis/exfoliative dermatitis (8%), hypermagnesemia (8%), hyperuricemia (8%), hypocalcemia (6%), nausea (6%), and pruritus (6%).
Infections were the most common type of serious adverse event reported in both Study 1 (N=102) and Study 2 (N=83) with 8 patients (8%) in Study 1 and 26 patients (31%) in Study 2 experiencing a serious infection.
The most common adverse reactions regardless of causality in Study 1 (N=102) were nausea (56%), asthenia/fatigue (53%), infections (46%), vomiting (34%), and anorexia (23%), and in Study 2 (N=83) were nausea (86%), asthenia/fatigue (77%), anemia (72%), thrombocytopenia (65%), ECG ST-T wave changes (63%), neutropenia (57%), lymphopenia (57%), infections (54%), anorexia (54%), vomiting (52%), hypocalcemia (52%), hyperglycemia (51%), hypoalbuminemia (48%), leukopenia (46%), dysgeusia (40%), and constipation (39%).
Monitor more frequently prothrombin time and International Normalized Ratio in patients concurrently administered ISTODAX and warfarin or coumarin derivatives
Romidepsin is metabolized by CYP3A4
Monitor patients for toxicity related to increased romidepsin exposure and follow dose modifications for toxicity when ISTODAX is initially co-administered with strong CYP3A4 inhibitors
Avoid co-administration of ISTODAX (romidepsin) with rifampin and other potent inducers of CYP3A4
Exercise caution with concomitant use of ISTODAX and P-glycoprotein (P-gp, ABCB1) inhibitors
USE IN SPECIFIC POPULATIONS
Pregnancy Category D: If this drug is used during pregnancy, or if the patient becomes pregnant while taking ISTODAX, the patient should be apprised of the potential hazard to the fetus
Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from ISTODAX, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother
Patients with moderate and severe hepatic impairment and/or patients with end-stage renal disease should be treated with caution