CLINICAL NEWS
• BV plus bendamustine : 15 CRs ( 88 %) and 2 PRs ( 12 %)
After a median follow-up of 21.6 months ( range = 14.8-29.0 months ) in the BV plus dacarbazine cohort , the median progressionfree survival ( PFS ) was 17.9 months ( range = 4.2-29 months ). Overall survival ( OS ) was not reached ( range = 14.8-29.0 + months ). After a median follow-up of 10.8 months ( range = 2.9-18.2 months ) in the
Females and Males of Reproductive Potential
Pregnancy Testing VYXEOS can cause fetal harm when administered to a pregnant woman [ see Use in Specific Populations ]. Verify the pregnancy status of females of reproductive potential prior to initiating VYXEOS .
Contraception
Females Advise females of reproductive potential to use effective contraception during treatment with VYXEOS and for at least 6 months after the last dose .
Males Advise males with female partners of reproductive potential to use effective contraception during treatment with VYXEOS and for at least 6 months after the last dose .
Infertility Based on findings of daunorubicin and cytarabine in animals , male fertility may be compromised by treatment with VYXEOS .
Pediatric Use Safety and effectiveness of VYXEOS in pediatric patients have not been established .
Geriatric Use Of the 375 patients who received VYXEOS ( daunorubicin 44 mg / m 2 and cytarabine 100 mg / m 2 ) liposome in clinical studies , 57 % were 65 years and over . No overall differences in safety were observed between these patients and younger patients , with the exception of bleeding events , which occurred more frequently in patients 65 years and older compared to younger patients ( 77 % vs . 59 %).
Renal Impairment Dosage adjustment is not required for patients with mild ( creatinine clearance [ CL CR
] 60 mL / min to 89 mL / min by Cockcroft Gault equation [ C-G ]) or moderate ( CL CR
30 mL / min to 59 mL / min ) renal impairment . VYXEOS has not been studied in patients with severe renal impairment ( CL CR
15 mL / min to 29 mL / min ) or end-stage renal disease .
Hepatic Impairment Dosage adjustment is not required for patients with a bilirubin level less than or equal to 3 mg / dL . VYXEOS has not been studied in patients with bilirubin level greater than 3 mg / dL .
PATIENT COUNSELING INFORMATION
Hemorrhage Inform patients of the risk of fatal bleeding . Advise patients of the need for periodic monitoring of blood counts and of the importance of keeping scheduled appointments for blood work and necessary transfusions . Advise patients to contact a healthcare provider for new onset fever or symptoms of infection or if they notice signs of bruising or bleeding [ see Warnings and Precautions and Adverse Reactions ].
BV plus bendamustine cohort , neither the median PFS ( range = 2.9-18 + months ) or OS ( range = 2.9-18.2 + months ) were reached .
By February 2016 , all patients were off treatment . Nineteen patients ( 86 %) treated with BV plus dacarbazine and 13 patients ( 65 %) treated with BV plus bendamustine are still being followed . More than half of patients ( 55 % in BV plus dacarbazine group and 60 % in BV plus bendamustine group ) had discontinued treatment because of AEs . One patient ( 5 %) in the BV plus dacarbazine group and six patients ( 30 %) in the BV plus bendamustine group died during follow-up .
After observing early toxicity in the first five patients who completed one treatment cycle of BV plus bendamustine , the study ’ s Safety Monitoring Committee recommended reducing the bendamustine dose to 70 mg / m 2 . “ Thirty patients were
Embryo-Fetal Toxicity VYXEOS can cause fetal harm when administered during pregnancy . Advise females of reproductive potential to use effective contraception during treatment and for 6 months following the last dose of VYXEOS and to inform their healthcare provider of a known or suspected pregnancy before and during treatment with VYXEOS [ see Warnings and Precautions and Use in Specific Populations ].
Lactation Advise patients not to breastfeed during treatment with VYXEOS and for at least 2 weeks after the last dose [ see Use in Specific Populations ].
Infertility Advise males of reproductive potential that VYXEOS may cause temporary or permanent infertility [ see Use in Specific Populations ].
Concomitant Medications Advise patients to speak with their physicians about any other medication they are currently taking [ see Drug Interactions ]. to receive BV plus bendamustine ,” the authors reported , “ however , serious AE incidence ( 65 %) and two deaths on study led to discontinuation of bendamustine treatment and cessation of enrollment in this arm .”
All patients receiving BV plus dacarbazine experienced at least one treatment-related AE , with nearly half ( 45 %) experiencing a grade ≥3 AE , and 18 percent experiencing a serious AE . The most common AE in this cohort was peripheral sensory neuropathy ( 77 %). However , while “ BV plus dacarbazine was well-tolerated overall , with a similar toxicity profile to BV monotherapy ,” the authors wrote , “ BV plus bendamustine treatment [ was associated with ] an unacceptably high rate of serious AEs and deaths .”
In the BV plus bendamustine cohort , 95 percent of patients ( n = 19 ) experienced at least one treatmentrelated AE , with 90 percent of patients ( n = 18 ) experiencing a grade ≥3 AE . The most common AE in this patient cohort was diarrhea ( 85 %).
“ Although the study was not designed to compare treatment arms ,” the authors cautioned , they reported that a higher incidence of specific treatment-related AEs , including diarrhea , asthenia / fatigue , hypokalemia , dehydration , weight decrease , hypotension , neutropenia , candidiasis , and pneumonia , and grade ≥3 AEs were observed in the BV plus bendamustine cohort than in the BV plus dacarbazine or the previously published BV monotherapy cohorts .
“ The combination of BV [ plus ] bendamustine is too toxic for elderly patients at the ages , dose levels , and frequencies studied ,” the authors concluded . But , “ these results suggest BV [ plus dacarbazine ] may be a treatment option for elderly patients with newly diagnosed HL .” These findings need to be confirmed in larger trials , they added .
The study is limited by its nonrandomized design , small patient cohort , and limited follow-up .
Seattle Genetics , Inc ., contributed to the production of the study . ●
The authors report receiving funding from Seattle Genetics , Inc .
REFERENCE
Friedberg JW , Forero-Torres A , Bordoni RE , et al . Frontline brentuximab vedotin in combination with dacarbazine or bendamustine in patients aged ≥60 years with HL . Blood . 2017 October 16 . [ Epub ahead of print ]
Cardiotoxicity Advise patients to contact their healthcare provider if they develop symptoms of heart failure [ see Warnings and Precautions ].
Hypersensitivity Reactions
Inform patients of the risk of hypersensitivity reactions , including anaphylaxis . Describe the symptoms of hypersensitivity reactions , including anaphylaxis , and instruct the patient to seek medical attention immediately if they experience such symptoms [ see Warnings and Precautions ]. © 2017 Jazz Pharmaceuticals VYX-0036 ( 1 ) a Rev0817
ASH Clinical News 57