Because 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 pooled safety population described in the WARNINGS AND PRECAUTIONS reflect exposure to LYMPHIR as a single agent in 119 patients with CTCL across 3 clinical trials. Patients received treatment with LYMPHIR as an intravenous infusion at 9 mcg/kg daily from Day 1 through Day 5 of each 21-day cycle until disease progression or unacceptable toxicity. Among 119 patients who received LYMPHIR the median number of cycles received was 5 (range: 1 to 42), with 13% exposed for 6 months or longer.
In this pooled safety population, the most common (≥ 20%) adverse reactions, including laboratory abnormalities, were increased transaminases (70%), albumin decreased (53%), nausea (40%), edema (35%), hemoglobin decreased (34%), fatigue (30%), musculoskeletal pain (26%), rash (23%), chills (22%), constipation (22%), pyrexia (21%), and capillary leak syndrome (20%).
The safety of LYMPHIR was evaluated in Study 302, an open-label, single-arm, multicenter trial that included 69 patients with relapsed or refractory Stage I-III CTCL [see Clinical Studies ( 14)] . Patients received treatment with LYMPHIR 9 mcg/kg daily from Day 1 through Day 5 of each 21-day cycle. Treatment was administered until disease progression or unacceptable toxicity. The median number of LYMPHIR cycles was 6 (range: 1 to 42).
The median age of patients was 64 years (range: 28 to 87 years), 49% were 65 years of age or older, 65% were men, 72% were White, 19% were Black or African American, 1.4% were Asian, and 14% were Hispanic or Latino.
Serious adverse reactions occurred in 38% of patients who received LYMPHIR. Serious adverse reactions in > 2% of patients included capillary leak syndrome (10%), infusion-related reaction (9%), sepsis (7%), skin infection (2.9%), pyrexia (2.9%), and rash (2.9%).
Permanent discontinuation of LYMPHIR due to an adverse reaction occurred in 12% of patients. Adverse reactions resulting in permanent discontinuation of LYMPHIR included capillary leak syndrome, infusion-related reaction, renal insufficiency, respiratory failure, and sepsis.
Dosage interruptions of LYMPHIR due to an adverse reaction occurred in 38% of patients. Adverse reactions requiring dosage interruption of LYMPHIR included capillary leak syndrome, infusion-related reaction, weight increase, nausea, and tachycardia.
Table 3 summarizes the adverse reactions in Study 302.
#Only Grade 3 adverse reaction occurred
aIncludes fatigue, asthenia, and lethargy
bIncludes edema, edema peripheral, generalized edema, face edema, swelling face, peripheral swelling
cIncludes musculoskeletal pain, back pain, neck pain, pain in extremity, myalgia, bone pain
dIncludes headache, migraine
eIncludes amnesia, confusional state, delirium, memory impairment, disturbance in attention, somnolence, cognitive disorder
fIncludes rash, drug eruption, erythema, rash maculo-papular, rash papular, rash pustular, rash pruritic, dermatitis exfoliative generalized, acute generalized exanthematous pustulosis
gIncludes skin infection, skin bacterial infection, staphylococcal skin infection, impetigo
hIncludes acute kidney injury, blood creatinine increased
Clinically relevant adverse reactions in < 10% of patients who received LYMPHIR included sepsis and peripheral neuropathy.
Table 4 summarizes select laboratory abnormalities in Study 302.
aGraded according to NCI CTCAE version 5.0
bThe denominator used to calculate the rate was 67 based on the number of patients with a baseline value and at least one post-treatment value
cPercentage of patients with an increase of at least 1 CTCAE grade from baseline to the worst post-baseline value of any grade, or to the worst post-baseline value that is Grade 3 or 4
dThe denominator used to calculate the rate was based on 36 patients with a baseline value and at least one post-treatment value.