ASH Clinical News ACN_4.3_FULL-ISSUE-DIGITAL | Page 8

We asked , and you answered ! Here are a few responses from this month ’ s “ You Make the Call .”

For the full description of the clinical dilemma , and to see how the expert responded , turn to page 63 .

Clinical Dilemma :

A 33-year-old transgender female patient was involved in a motor vehicle accident that resulted in severe liver laceration , bile duct injury , and a subdural hematoma . She required multiple surgeries and was hospitalized for 91 days , followed by inpatient rehabilitation . At the time of the accident , she was on hormone replacement therapy ( HRT ), which was stopped during her stay in the intensive care unit . About 26 days into her hospitalization , she had a deep vein thrombosis ( DVT ) and pulmonary embolism . She had an inferior vena cava ( IVC ) filter placed and was started on anticoagulation . Will she be able to go back on HRT ? Would you consider lifelong anticoagulation in this patient who needs HRT ? She had been on HRT for eight years with no problems prior to this event . There is no family history of thromboembolic disease .

CALQUENCE ® ( acalabrutinib ) capsules , for oral use Initial U . S . Approval : 2017

Brief Summary of Prescribing Information . For complete prescribing information consult official package insert .

INDICATIONS AND USAGE CALQUENCE is indicated for the treatment of adult patients with mantle cell lymphoma ( MCL ) who have received at least one prior therapy .

This indication is approved under accelerated approval based on overall response rate [ see Clinical Studies ( 14 ) in the full Prescribing Information ]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials .

DOSAGE AND ADMINISTRATION

Recommended Dosage The recommended dose of CALQUENCE is 100 mg taken orally approximately every twelve hours until disease progression or unacceptable toxicity .

Advise patients to swallow capsule whole with water . Advise patients not to open , break or chew the capsules . CALQUENCE may be taken with or without food . If a dose of CALQUENCE is missed by more than 3 hours , it should be skipped and the next dose should be taken at its regularly scheduled time . Extra capsules of CALQUENCE should not be taken to make up for a missed dose .

Dose Modifications

Adverse Reactions Recommended dose modifications of CALQUENCE for Grade 3 or greater adverse reactions are provided in Table 1 .

Table 1 : Recommended Dose Modifications for Adverse Reactions

Event

Grade 3 or greater non-hematologic toxicities ,

Grade 3 thrombocytopenia with bleeding ,

Grade 4 thrombocytopenia or

Grade 4 neutropenia lasting longer than 7 days

Adverse Reaction Occurrence

First and Second

Third

Dose Modification ( Starting dose = 100 mg twice daily )

Interrupt CALQUENCE . Once toxicity has resolved to Grade 1 or baseline level , CALQUENCE therapy may be resumed at 100 mg twice daily .

Interrupt CALQUENCE . Once toxicity has resolved to Grade 1 or baseline level , CALQUENCE therapy may be resumed at 100 mg daily .

Fourth Discontinue CALQUENCE .

Concomitant Use with Gastric Acid Reducing Agents Proton Pump Inhibitors : Avoid concomitant use [ see Drug Interactions ( 7 ) in the full Prescribing Information ].

H2-Receptor Antagonists : Take CALQUENCE 2 hours before taking a H2-receptor antagonist [ see Drug Interactions ( 7 ) in the full Prescribing Information ].

Antacids : Separate dosing by at least 2 hours [ see Drug Interactions ( 7 ) in the full Prescribing Information ].

CONTRAINDICATIONS None .

WARNINGS AND PRECAUTIONS

Hemorrhage Serious hemorrhagic events , including fatal events , have occurred in the combined safety database of 612 patients with hematologic malignancies treated with CALQUENCE monotherapy . Grade 3 or higher bleeding events , including gastrointestinal , intracranial , and epistaxis have been reported in 2 % of patients . Overall , bleeding events including bruising and petechiae of any grade occurred in approximately 50 % of patients with hematological malignancies .

The mechanism for the bleeding events is not well understood . CALQUENCE may further increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and patients should be monitored for signs of bleeding . Consider the benefit-risk of withholding CALQUENCE for 3-7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding .

Infection Serious infections ( bacterial , viral or fungal ), including fatal events and opportunistic infections have occurred in the combined safety database of 612 patients with hematologic malignancies treated with CALQUENCE monotherapy . Consider prophylaxis in patients who are at increased risk for opportunistic infections .

Grade 3 or higher infections occurred in 18 % of these patients . The most frequently reported Grade 3 or 4 infection was pneumonia . Infections due to hepatitis B virus ( HBV ) reactivation and progressive multifocal leukoencephalopathy ( PML ) have occurred . Monitor patients for signs and symptoms of infection and treat as medically appropriate .

Cytopenias In the combined safety database of 612 patients with hematologic malignancies , patients treated with CALQUENCE monotherapy experienced Grade 3 or 4 cytopenias , including neutropenia ( 23 %), anemia ( 11 %) and thrombocytopenia ( 8 %) based on laboratory measurements . In the CALQUENCE clinical Trial LY-004 , patients ’ complete blood counts were assessed monthly during treatment .

Second Primary Malignancies Second primary malignancies , including non-skin carcinomas , have occurred in 11 % of patients with hematologic malignancies treated with CALQUENCE monotherapy in the combined safety database of 612 patients . The most frequent second primary malignancy was skin cancer , reported in 7 % of patients . Advise protection from sun exposure .

Atrial Fibrillation and Flutter In the combined safety database of 612 patients with hematologic malignancies treated with CALQUENCE monotherapy , atrial fibrillation and atrial flutter of any grade occurred in 3 % of patients , and Grade 3 in 1 % of patients . Monitor for atrial fibrillation and atrial flutter and manage as appropriate .

ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling :

• Hemorrhage [ see Warnings and Precautions ( 5.1 ) in the full Prescribing Information ]

• Infection [ see Warnings and Precautions ( 5.2 ) in the full Prescribing Information ]

• Cytopenias [ see Warnings and Precautions ( 5.3 ) in the full Prescribing Information ]

• Second Primary Malignancies [ see Warnings and Precautions ( 5.4 ) in the full Prescribing Information ]

• Atrial Fibrillation and Flutter [ see Warnings and Precautions ( 5.5 ) in the full Prescribing Information ]

Clinical Trials Experience As 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 practice .

The safety data described in this section reflect exposure to CALQUENCE ( 100 mg twice daily ) in 124 patients with previously treated MCL in Trial LY-004 [ see Clinical Studies ( 14 ) in the full Prescribing Information ]. The median duration of treatment with CALQUENCE was 16.6 ( range 0.1 to 26.6 ) months . A total of 91 ( 73.4 %) patients were treated with CALQUENCE for ≥ 6 months and 74 ( 59.7 %) patients were treated for ≥ 1 year .

The most common adverse reactions ( ≥ 20 %) of any grade were anemia , thrombocytopenia , headache , neutropenia , diarrhea , fatigue , myalgia , and bruising . Grade 1 severity for the non-hematologic , most common events were as follows : headache ( 25 %), diarrhea ( 16 %), fatigue ( 20 %), myalgia ( 15 %), and bruising ( 19 %). The most common Grade ≥ 3 non-hematological adverse reaction ( reported in at least 2 % of patients ) was diarrhea .

Dose reductions or discontinuation due to any adverse reaction were reported in 1.6 % and 6.5 % of patients , respectively .

Tables 2 and 3 present the frequency category of adverse reactions observed in patients with MCL treated with CALQUENCE .

Table 2 : Non-Hematologic Adverse Reactions * in ≥ 5 % ( All Grades ) of Patients with MCL in Trial LY-004

Body System Adverse Reactions

CALQUENCE 100 mg twice daily N = 124

All Grades (%) Grade ≥ 3 (%)