Adverse reactions
The following adverse reactions are described elsewhere in the labeling: Cytokine Release Syndrome [see Warnings and Precautions (5.1) ] Neurologic Toxicity, including Immune Effector Cell-associated Neurotoxicity Syndrome [see Warnings and Precautions (5.2) ] Infections [see Warnings and Precautions (5.3) ] Hemophagocytic Lymphohistiocytosis [see Warnings and Precautions (5.4) ] Cytopenias [see Warnings and Precautions (5.5) ] Tumor Flare [see Warnings and Precautions (5.6) ] The most common adverse reactions (≥ 20%) in patients with follicular lymphoma are CRS, fatigue, rash, headache, pyrexia, musculoskeletal pain, cough, pruritus, and peripheral neuropathy.
The most common Grade 3 to 4 laboratory abnormalities (≥ 10%) are decreased lymphocyte count, decreased phosphate, increased glucose, decreased neutrophil count, increased uric acid, decreased hemoglobin, and decreased platelets. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience
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 reflects exposure to LUNSUMIO as a single agent in GO29781 in 218 patients with hematologic malignancies in an open-label, multicenter, multi-cohort study.
Patients received step-up doses of 1 mg on Cycle 1 Day 1 and 2 mg on Cycle 1 Day 8, followed by 60 mg on Cycle 1 Day 15, and 60 mg on Cycle 2 Day 1, then 30 mg every 3 weeks in subsequent cycles. Each treatment cycle was 21 days. Among 218 patients who received LUNSUMIO, 52% were exposed for at least 8 cycles and 8% were exposed for 17 cycles. In this pooled safety population, the most common (≥ 20%) adverse reactions were CRS (39%), fatigue (36%), rash (34%), pyrexia (24%), and headache (21%).
The most common Grade 3 to 4 laboratory abnormalities (≥ 10%) were decreased lymphocyte count (92%), decreased phosphate (41%), increased glucose (40%), decreased neutrophil count (38%), decreased hemoglobin (19%), increased uric acid (15%), and decreased platelets (12%). Relapsed or Refractory Follicular Lymphoma The safety of LUNSUMIO was evaluated in GO29781, an open-label, multicenter, multi-cohort study which included a cohort of 90 patients with relapsed or refractory follicular lymphoma (FL) [see Clinical Studies (14) ] .
In this cohort, patients with relapsed or refractory FL were required to have received at least two prior lines of systemic therapy, including an anti-CD20 monoclonal antibody and an alkylating agent. Patients received step-up doses of 1 mg on Cycle 1 Day 1 and 2 mg on Cycle 1 Day 8, followed by 60 mg on Cycle 1 Day 15 and 60 mg on Cycle 2 Day 1, then 30 mg every 3 weeks in subsequent cycles. A treatment cycle was 21 days.
The median number of cycles was 8 (range: 1 to 17). In the relapsed or refractory FL cohort, 77% were exposed for at least 8 cycles and 12% were exposed for 17 cycles. The median age was 60 years (range: 29 to 90 years), 61% were male, 82% were White, 4% were Black or African American, 9% were Asian, and 8% were Hispanic or Latino. Serious adverse reactions occurred in 47% of patients who received LUNSUMIO. Serious adverse reactions in ≥ 2% of patients included CRS, infection (including sepsis, pneumonia, urinary tract infection, EBV viremia, COVID-19, and upper respiratory tract infection), renal insufficiency, pyrexia, and tumor flare.
Permanent discontinuation of LUNSUMIO due to an adverse reaction occurred in 3% of patients. Adverse reactions resulting in permanent discontinuation of LUNSUMIO included CRS and EBV viremia. Dosage interruptions of LUNSUMIO due to an adverse reaction occurred in 37% of patients. Adverse reactions which required dosage interruption in ≥ 5% of patients included neutropenia, infection, and CRS. Table 8 summarizes the adverse reactions in patients with relapsed or refractory FL treated with LUNSUMIO in GO29781.
Table 8. Adverse Reactions (≥ 10%) in Patients with Relapsed or Refractory FL Who Received LUNSUMIO Intravenous Infusion in GO29781 Adverse Reaction Adverse reactions were graded based on CTCAE Version 4.0, with the exception of CRS, which was graded per ASTCT 2019 criteria. LUNSUMIO (N = 90) All Grades (%) Grade 3 or 4 (%) Immune system disorders Cytokine release syndrome 44
2.2 General disorders and administration site conditions Fatigue Fatigue includes fatigue, asthenia, and lethargy. 42 0 Pyrexia 29
1.1Only Grade
3 adverse reactions occurred. Edema Edema includes edema, edema peripheral, peripheral swelling, face edema, swelling face, pulmonary edema, fluid overload, and fluid retention. 17
1.1Skin
and subcutaneous tissue disorders Rash Rash includes rash, rash erythematous, exfoliative rash, rash macular, rash maculo-papular, rash papular, rash pruritic, rash pustular, erythema, palmar erythema, dermatitis, and dermatitis acneiform. 39
4.4Pruritus 21 0
Dry skin 16 0 Skin exfoliation 10 0 Nervous system Headache Headache includes headache and migraine. 32
1.1 Peripheral neuropathy Peripheral neuropathy includes peripheral neuropathy, peripheral sensory neuropathy, paresthesia, dysesthesia, hypoesthesia, burning sensation, and neuralgia. 20 0 Dizziness Dizziness includes dizziness and vertigo. 12 0 Musculoskeletal and connective tissue disorders Musculoskeletal pain Musculoskeletal pain includes musculoskeletal pain, back pain, myalgia, musculoskeletal chest pain, and neck pain. 28
1.1Arthralgia 11 0
Respiratory, thoracic, and mediastinal disorders Cough Cough includes cough, productive cough, and upper airway cough syndrome. 22 0 Dyspnea Dyspnea includes dyspnea and dyspnea exertional. 11
1.1 Gastrointestinal disorders Diarrhea 17 0 Nausea 17 0 Abdominal pain Abdominal pain includes abdominal pain, lower abdominal pain, and abdominal discomfort. 12
1.1Infections
Upper respiratory tract infection Upper respiratory tract infection includes upper respiratory tract infection, nasopharyngitis, sinusitis, and rhinovirus infection. 14
2.2 Urinary tract infection Urinary tract infection includes urinary tract infection and acute pyelonephritis. 10
1.1 Psychiatric disorder Insomnia 12 0 Clinically relevant adverse reactions in < 10% of patients who received LUNSUMIO included pneumonia, sepsis, COVID-19, EBV viremia, mental status changes, tumor lysis syndrome, renal insufficiency, anxiety, motor dysfunction (including ataxia, gait disturbance and tremor), tumor flare, and ICANS. Table 9 summarizes the laboratory abnormalities in patients with relapsed or refractory FL treated with LUNSUMIO in GO29781.
Table 9. Select Laboratory Abnormalities (≥ 20%) That Worsened from Baseline in Patients with Relapsed or Refractory FL Who Received LUNSUMIO Intravenous Infusion in GO29781 Laboratory Abnormality LUNSUMIO The denominator used to calculate the rate varied from 72 to 90 based on the number of patients with a baseline value and at least one post-treatment value. All Grades (%) Grade 3 or 4 (%) Hematology Lymphocyte count decreased 100 98 Hemoglobin decreased 68 12 Neutrophils decreased 58 40 Platelets decreased 46 10 Chemistry Phosphate decreased 78 46 Glucose increased 42 42 Aspartate aminotransferase increased 39
4.4 Gamma-glutamyl transferase increased 34 9 Magnesium decreased 34 0 Potassium decreased 33 6 Alanine aminotransferase increased 32 7 Uric acid increased 22 22
