nsaminases and/or bilirubin, have occurred in patients treated with POLIVY.In recipients of POLIVY in Study GO29365 (n = 173), Grade 3 and 4 transaminase elevationsdeveloped in 1.9% and 1.9%, respectively. Laboratory values suggestive of drug-induced liverinjury (both an ALT or AST greater than 3 times upper limit of normal [ULN] and total bilirubingreater than 2 times ULN) occurred in 2.3% of patients.
Preexisting liver disease, elevated baseline liver enzymes, and concomitant medications mayincrease the risk of hepatotoxicity. Monitor liver enzymes and bilirubin level.
5.8 Embryo-Fetal Toxicity
Based on the mechanism of action and findings from animal studies, POLIVY can cause fetalharm when administered to a pregnant woman. The small molecule component of POLIVY,MMAE, administered to rats caused adverse developmental outcomes, including embryo-fetalmortality and structural abnormalities, at exposures below those occurring clinically at therecommended dose.
Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potentialto use effective contraception during treatment with POLIVY and for at least 3 months after thelast dose. Advise male patients with female partners of reproductive potential to use effectivecontraception during treatment with POLIVY and for at least 5 months after the last dose [seeUse in Specific Populations (8.1, 8.3), Clinical Pharmacology (12.1)].
6 ADVERSE REACTIONS
The following clinically significant adverse reactions are discussed in greater detail in othersections of the label:
Peripheral Neuropathy [see Warnings and Precautions (5.1)]
Infusion-Related Reactions [see Warnings and Precautions (5.2)]
Myelosuppression [see Warnings and Precautions (5.3)]
Serious and Opportunistic Infections [see Warnings and Precautions (5.4)]
Progressive Multifocal Leukoencephalopathy [see Warnings and Precautions (5.5)]
Tumor Lysis Syndrome [see Warnings and Precautions (5.6)]
Hepatotoxicity [see Warnings and Precautions (5.7)]
6.1 Clinical Trial Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction ratesobserved in the clinical trials of a drug cannot be directly compared with rates in the clinicaltrials of another drug and may not reflect the rates observed in practice.
The data described in this section reflect exposure to POLIVY in Study GO29365, a multicenterclinical trial for adult patients with relapsed or refractory B-cell lymphomas [see Clinical Studies(14)]. In patients with relapsed or refractory DLBCL, the trial included a single-arm safetyeva luation of POLIVY in combination with bendamustine and a rituximab product (BR) (n = 6),followed by an open-label randomization to POLIVY in combination with BR versus BR alone(n = 39 treated per arm).
Following premedication with an antihistamine and antipyretic, POLIVY 1.8 mg/kg wasadministered by intravenous infusion on Day 2 of Cycle 1 and on Day 1 of Cycles 2–6, with acycle length of 21 days. Bendamustine 90 mg/m2daily was administered intravenously on Days2 and 3 of Cycle 1 and on Days 1 and 2 of Cycles 2–6. A rituximab product dosed at 375 mg/m2was administered intravenously on Day 1 of each cycle. Granulocyte colony stimulating factorprimary prophylaxis was optional and administered to 42% of recipients of POLIVY plus BR.
In POLIVY treated patients (n = 45), the median age was 67 years (range 33 – 86) with 58%being & |
