ASH Clinical News May 2017 NEW | Page 32

Written in Blood
Continued from page 24

Venetoclax Plus Obinutuzumab Effective in Older Adults With CLL and Comorbidities

Patients with chronic lymphocytic leukemia ( CLL ) are often older at the time of diagnosis ( median age = 72 years ), and typically receive treatment for coexisting medical conditions . In a Letter to the Editor published in Blood , Kirsten Fischer , MD , from the Center for Integrated Oncology
Cologne-Bonn at the University Hospital Cologne in Germany , and co-authors reported results from the ongoing phase III CLL14 trial , which is comparing the safety and efficacy of obinutuzumab with either chlorambucil or venetoclax in older patients with CLL .
Dr . Fischer and colleagues shared results from the venetoclax-treated arm of the study , which enrolled 13 adult patients with previously untreated CLL ( median age = 75 years ; range = 59-88 years ) from Australia , Canada , Germany , New Zealand , the United States , and Spain between December 2014 and April 2015 . All patients responded to treatment with venetoclax and obinutuzumab , and more than half of the 12 patients who completed treatment ( 58 %; n = 7 / 12 ) had a complete response ( per International Workshop on CLL guidelines ).
Patients were included in the trial if they had a cumulative illness rating scale ( CIRS ) score of > 6 ( indicating the presence of multiple comorbidities ) and , at baseline , patients had a median CIRS score of 8 ( range = 6-14 ).
Patients received six cycles of intravenous obinutuzumab ( cycle 1 : either
REVLIMID [ lenalidomide ] capsules , for oral use
The following is a Brief Summary ; refer to full Prescribing Information for complete product information .
WARNING : EMBRYO-FETAL TOXICITY , HEMATOLOGIC TOXICITY , and VENOUS and ARTERIAL THROMBOEMBOLISM
Embryo-Fetal Toxicity Do not use REVLIMID during pregnancy . Lenalidomide , a thalidomide analogue , caused limb abnormalities in a developmental monkey study . Thalidomide is a known human teratogen that causes severe life-threatening human birth defects . If lenalidomide is used during pregnancy , it may cause birth defects or embryo-fetal death . In females of reproductive potential , obtain 2 negative pregnancy tests before starting REVLIMID ® treatment . Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after REVLIMID treatment [ see Warnings and Precautions ( 5.1 ), and Medication Guide ( 17 )]. To avoid embryofetal exposure to lenalidomide , REVLIMID is only available through a restricted distribution program , the REVLIMID REMS ® program ( 5.2 ).
Information about the REVLIMID REMS program is available at www . celgeneriskmanagement . com or by calling the manufacturer ’ s toll-free number 1-888-423-5436 .
Hematologic Toxicity ( Neutropenia and Thrombocytopenia ) REVLIMID can cause significant neutropenia and thrombocytopenia . Eighty percent of patients with del 5q myelodysplastic syndromes had to have a dose delay / reduction during the major study . Thirty-four percent of patients had to have a second dose delay / reduction . Grade 3 or 4 hematologic toxicity was seen in 80 % of patients enrolled in the study . Patients on therapy for del 5q myelodysplastic syndromes should have their complete blood counts monitored weekly for the first 8 weeks of therapy and at least monthly thereafter . Patients may require dose interruption and / or reduction . Patients may require use of blood product support and / or growth factors [ see Dosage and Administration ( 2.1 )].
Venous and Arterial Thromboembolism REVLIMID has demonstrated a significantly increased risk of deep vein thrombosis ( DVT ) and pulmonary embolism ( PE ), as well as risk of myocardial infarction and stroke in patients with multiple myeloma who were treated with REVLIMID and dexamethasone therapy . Monitor for and advise patients about signs and symptoms of thromboembolism . Advise patients to seek immediate medical care if they develop symptoms such as shortness of breath , chest pain , or arm or leg swelling . Thromboprophylaxis is recommended and the choice of regimen should be based on an assessment of the patient ’ s underlying risks [ see Warnings and Precautions ( 5.4 )].
1 INDICATIONS AND USAGE 1.1 Multiple Myeloma
REVLIMID is indicated as maintenance therapy in patients with MM following autologous hematopoietic stem cell transplantation ( auto-HSCT ).
1.4 Limitations of Use :
REVLIMID is not indicated and is not recommended for the treatment of patients with CLL outside of controlled clinical trials [ see Warnings and Precautions ( 5.5 )].
2 DOSAGE AND ADMINISTRATION
REVLIMID should be taken orally at about the same time each day , either with or without food . REVLIMID capsules should be swallowed whole with water . The capsules should not be opened , broken , or chewed .
2.1 Multiple Myeloma REVLIMID Maintenance Therapy Following Auto-HSCT
Following auto-HSCT , initiate REVLIMID maintenance therapy after adequate hematologic recovery ( ANC ≥ 1000 / mcL and / or platelet counts ≥75,000 / mcL ). The recommended starting dose of REVLIMID is 10 mg once daily continuously ( Days 1-28 of repeated 28-day cycles ) until disease progression or unacceptable toxicity . After 3 cycles of maintenance therapy , the dose can be increased to 15 mg once daily if tolerated .
Dose Adjustments for Hematologic Toxicities During MM Treatment
Dose modification guidelines , as summarized in Table 2 below , are recommended to manage Grade 3 or 4 neutropenia or thrombocytopenia or other Grade 3 or 4 toxicity judged to be related to REVLIMID .
Table 2 : Dose Adjustments for Hematologic Toxicities for MM Platelet counts Thrombocytopenia in MM When Platelets
Recommended Course
Fall to < 30,000 / mcL
Interrupt REVLIMID treatment , follow CBC weekly
Return to ≥30,000 / mcL Resume REVLIMID at next lower dose , continuously for Days 1-28 of repeated 28-day cycle
If at the 5 mg daily dose , Interrupt REVLIMID treatment . Do not For a subsequent drop < 30,000 / mcL dose below 5 mg daily for Day 1 to 21 of 28 day cycle
Return to ≥30,000 / mcL
Resume REVLIMID at 5 mg daily for Days 1 to 21of 28-day cycle . Do not dose below 5 mg daily for Day 1 to 21 of 28 day cycle
Absolute Neutrophil counts ( ANC ) Neutropenia in MM When Neutrophils
Recommended Course
Fall to < 500 / mcL Interrupt REVLIMID treatment , follow
Return to ≥500 / mcL
CBC weekly Resume REVLIMID at next lower dose , continuously for Days 1-28 of repeated 28-day cycle
If at 5 mg daily dose ,
Interrupt REVLIMID treatment . Do not For a subsequent drop < 500 / mcL dose below 5 mg daily for Days 1 to
21 of 28-day cycle
Return to > 500 / mcL Resume REVLIMID at 5 mg daily for Days 1 to 21 of 28-day cycle . Do not dose below 5 mg daily for Days 1 to 21 of 28-day cycle
Other Toxicities in MM
For other Grade 3 / 4 toxicities judged to be related to REVLIMID , hold
treatment and restart at the physician ’ s discretion at next lower dose level
when toxicity has resolved to ≤ Grade 2 .
Starting Dose Adjustment for Renal Impairment in MM :
[ See Dosage and Administration ( 2.4 )].
2.4 Starting Dose for Renal Impairment in MM
The recommendations for starting doses for patients with renal impairment
are shown in the following table
Table 3 : Starting Dose Adjustments for Patients with Renal Impairment
Renal Function
Dose in REVLIMID
Dose in REVLIMID
( Cockcroft-Gault )
Combination Therapy for
Maintenance Therapy
MM and for MCL
Following Auto-HSCT for MM and for MDS
CLcr 30 to 60 mL / min 10 mg once daily
5 mg once daily
CLcr < 30 mL / min
15 mg every other day
2.5 mg once daily
( not requiring dialysis ) CLcr < 30 mL / min
5 mg once daily . On
2.5 mg once daily . On
( requiring dialysis )
dialysis days , administer
dialysis days , administer
the dose following dialysis . the dose following dialysis .
REVLIMID Maintenance Therapy Following Auto-HSCT for MM and for MCL and MDS : Base subsequent REVLIMID dose increase or decrease on individual patient treatment tolerance [ see Dosage and Administration ( 2.1- 2.3 )].
4 CONTRAINDICATIONS 4.1 Pregnancy
REVLIMID can cause fetal harm when administered to a pregnant female . Limb abnormalities were seen in the offspring of monkeys that were dosed with lenalidomide during organogenesis . This effect was seen at all doses tested . Due to the results of this developmental monkey study , and lenalidomide ’ s structural similarities to thalidomide , a known human teratogen , lenalidomide is contraindicated in females who are pregnant [ see Boxed Warning ]. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug , the patient should be apprised of the potential hazard to the fetus [ see Warnings and Precautions ( 5.1 , 5.2 ), Use in Special Populations ( 8.1 ), ( 8.6 )].