ASH Clinical News ACN_4.13_full issue_Web | Page 33

CLINICAL NEWS
instead found that the following factors
predicted the development of non–
catheter-related thrombosis, although p
values were not reported:
• age ≥60 years (HR=1.54; 95% CI
1.13-2.11)
• previous VTE (HR=2.68; 95% CI
1.85-3.89)
• hemoglobin levels <10 g/dL
(HR=2.07; 95% CI 1.37-3.12)
• leukocyte counts >11x10 9 cells/L prior
to chemotherapy initiation (HR=1.57;
95% CI 1.12-2.20)
“We did not find that previous VTE was a
risk factor for catheter-related thrombosis,
even though 14.8 percent of our patients
had such a medical history,” the authors
noted. “The reason for this may be that
mechanical factors are more important
than medical background in determining
the risk of specific events such as catheter-
related thrombosis.”
The disparity between the risk factors
for catheter-related and non–catheter-
related thrombosis suggests the need for
different prevention strategies. “Catheter-
related thrombosis may affect primarily
catheter function/permeability … thus,
IMPORTANT SAFETY INFORMATION (CONT’D)
Cutaneous Reactions (cont’d): mild or moderate (Grade 1-2) cutaneous reactions, continue COPIKTRA at the current dose, initiate
supportive care with emollients, antihistamines (for pruritus), or topical steroids, and monitor the patient closely. Withhold COPIKTRA for
severe (Grade 3) cutaneous reaction until resolution. Initiate supportive care with steroids (topical or systemic) or antihistamines (for
pruritus). Monitor at least weekly until resolved. Upon resolution of the event, restart COPIKTRA at a reduced dose. Discontinue
COPIKTRA if severe cutaneous reaction does not improve, worsens, or recurs. For life-threatening cutaneous reactions, discontinue
COPIKTRA. In patients with SJS, TEN, or DRESS of any grade, discontinue COPIKTRA.
Pneumonitis: Serious, including fatal (1/442; <1%), pneumonitis without an apparent infectious cause occurred in 5% of patients receiving
COPIKTRA 25 mg BID (N=442). Median time to onset of any grade pneumonitis was 4 months (range: 9 days to 27 months), with 75% of
cases occurring within 9 months. The median event duration was 1 month, with 75% of cases resolving by 2 months. Withhold COPIKTRA
in patients with new or progressive pulmonary signs and symptoms such as cough, dyspnea, hypoxia, interstitial infiltrates on a radiologic
exam, or a decline by more than 5% in oxygen saturation, and evaluate for etiology. If the pneumonitis is infectious, patients may be
restarted on COPIKTRA at the previous dose once the infection, pulmonary signs and symptoms resolve. For moderate non-infectious
pneumonitis (Grade 2), treat with systemic corticosteroids and resume COPIKTRA at a reduced dose upon resolution. If non-infectious
pneumonitis recurs or does not respond to steroid therapy, discontinue COPIKTRA. For severe or life-threatening non-infectious
pneumonitis, discontinue COPIKTRA and treat with systemic steroids.
Hepatotoxicity: Grade 3 and 4 ALT and/or AST elevation developed in 8% and 2%, respectively, of patients receiving COPIKTRA 25 mg
BID (N=442). Two percent of patients had both an ALT or AST >3 X ULN and total bilirubin >2 X ULN. Median time to onset of any grade
transaminase elevation was 2 months (range: 3 days to 26 months), with a median event duration of 1 month (range: 1 day to 16 months).
Monitor hepatic function during treatment with COPIKTRA. For Grade 2 ALT/AST elevation (>3 to 5 X ULN), maintain COPIKTRA dose and
monitor at least weekly until return to <3 X ULN. For Grade 3 ALT/AST elevation (>5 to 20 X ULN), withhold COPIKTRA and monitor at
least weekly until return to <3 X ULN. Resume COPIKTRA at the same dose (first occurrence) or at a reduced dose for subsequent
occurrences. For grade 4 ALT/AST elevation (>20 X ULN), discontinue COPIKTRA.
Neutropenia: Grade 3 or 4 neutropenia occurred in 42% of patients receiving COPIKTRA 25 mg BID (N=442), with Grade 4 neutropenia
occurring in 24% of all patients. Median time to onset of grade ≥3 neutropenia was 2 months (range: 3 days to 31 months), with 75% of
cases occurring within 4 months. Monitor neutrophil counts at least every 2 weeks for the first 2 months of COPIKTRA therapy, and at
least weekly in patients with neutrophil counts < 1.0 Gi/L (Grade 3-4). Withhold COPIKTRA in patients presenting with neutrophil counts
< 0.5 Gi/L (Grade 4). Monitor until ANC is > 0.5 Gi/L, then resume COPIKTRA at same dose for the first occurrence or at a reduced dose for
subsequent occurrences.
Embryo-Fetal Toxicity: Based on findings in animals and its mechanism of action, COPIKTRA can cause fetal harm when administered
to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Conduct pregnancy testing before initiating COPIKTRA
treatment. Advise females of reproductive potential and males with female partners of reproductive potential to use effective
contraception during treatment and for at least 1 month after the last dose.
ADVERSE REACTIONS
B-cell Malignancies Summary
Fatal adverse reactions within 30 days of the last dose occurred in 8% (36/442) of patients treated with COPIKTRA 25 mg BID. Serious
adverse reactions were reported in 289 patients (65%). The most frequent serious adverse reactions that occurred were infection (31%),
diarrhea or colitis (18%), pneumonia (17%), rash (5%), and pneumonitis (5%). Adverse reactions resulted in treatment discontinuation in 156
patients (35%) most often due to diarrhea or colitis, infection, and rash. COPIKTRA was dose reduced in 104 patients (24%) due to adverse
reactions, most often due to diarrhea or colitis and transaminase elevation. The most common adverse reactions (reported in ≥20% of
patients) were diarrhea or colitis, neutropenia, rash, fatigue, pyrexia, cough, nausea, upper respiratory infection, pneumonia, musculoskeletal
pain and anemia.
CLL/SLL
Fatal adverse reactions within 30 days of the last dose occurred in 12% (19/158) of patients treated with COPIKTRA and in 4% (7/155) of
patients treated with ofatumumab. Serious adverse reactions were reported in 73% (115/158) of patients treated with COPIKTRA and
most often involved infection (38%; 60/158) and diarrhea or colitis (23%; 36/158). COPIKTRA was discontinued in 57 patients (36%), most
often due to diarrhea or colitis, infection, and rash. COPIKTRA was dose reduced in 46 patients (29%) due to adverse reactions, most
often due to diarrhea or colitis and rash. The most common adverse reactions with COPIKTRA (reported in ≥20% of patients) were
diarrhea or colitis, neutropenia, pyrexia, upper respiratory tract infection, pneumonia, rash, fatigue, nausea, anemia and cough.
FL
Serious adverse reactions were reported in 58% of patients and most often involved diarrhea or colitis, pneumonia, renal insufficiency,
rash, and sepsis. The most common adverse reactions (≥20% of patients) were diarrhea or colitis, nausea, fatigue, musculoskeletal pain,
rash, neutropenia, cough, anemia, pyrexia, headache, mucositis, abdominal pain, vomiting, transaminase elevation, and
thrombocytopenia. Adverse reactions resulted in COPIKTRA discontinuation in 29% of patients, most often due to diarrhea or colitis and
rash. COPIKTRA was dose reduced in 23% due to adverse reactions, most often due to transaminase elevation, diarrhea or colitis, lipase
increased and infection.
DRUG INTERACTIONS
CYP3A Inducers: Coadministration with a strong CYP3A inducer may reduce COPIKTRA efficacy. Avoid coadministration with strong
CYP3A4 inducers.
CYP3A Inhibitors: Coadministration with a strong CYP3A inhibitor may increase the risk of COPIKTRA toxicities. Reduce COPIKTRA dose
to 15 mg BID when coadministered with a strong CYP3A4 inhibitor.
CYP3A Substrates: Coadministration of COPIKTRA with sensitive CYP3A4 substrates may increase the risk of toxicities of these drugs.
Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive
CYP3A substrate.
INDICATIONS AND USAGE
COPIKTRA™ (duvelisib) is indicated for:
The treatment of adult patients with relapsed or refractory CLL or SLL after at least two prior therapies
The treatment of adult patients with relapsed or refractory FL after at least two prior systemic therapies.
This indication is approved under accelerated approval based on overall response rate (ORR). Continued approval for this indication may
be contingent upon verification and description of clinical benefit in confirmatory trials.
Please see brief summary of full Prescribing Information on the following pages.
REFERENCES: 1. COPIKTRA Prescribing Information, Verastem, Inc. 2. Nicholas NS, Apollonio B, Ramsay AG. Tumor microenvironment (TME)-driven immune suppression
in B cell malignancy. Biochim Biophys Acta. 2016;1863(3):471-482.
Copyright © 2018 Verastem, Inc. All rights reserved. PM-US-DUV-18-0008. Printed in USA | October 2018
prevention of catheter-related thrombosis
may focus mainly on mechanical factors,
with the objective of protecting catheter
function,” the researchers explained. How-
ever, the prevention of VTE unrelated to
the catheter may “rely on anticoagulant
drugs to improve patient prognosis.”
The study did not include any patients
with a multilumen port, so the researchers
were unable to assess its thrombotic ef-
fects, they noted. The study’s implications