rrésyndrome. Use of systemic immunosuppressants for immune-mediated reactions wasreported in 1.9% (6/319) of recipients of POTELIGEO in Trial 1, including for a case of Grade 2polymyalgia rheumatica. New-onset hypothyroidism (Grade 1 or 2) was reported in 1.3% ofpatients and managed with observation or levothyroxine. Interrupt or permanently discontinuePOTELIGEO as appropriate for suspected immune-mediated adverse reactions. Consider thebenefit/risk of POTELIGEO in patients with a history of autoimmune disease.
5.5 Complications of Allogeneic Hematopoietic Stem Cell Transplantation(HSCT) after POTELIGEOIncreased risks of transplant complications have been reported in patients who receive allogeneicHSCT after POTELIGEO including severe (Grade 3 or 4) acute graft-versus-host disease(GVHD), steroid-refractory GVHD, and transplant-related death. Among recipients ofpre-transplantation POTELIGEO, a higher risk of transplant complications has been reported ifPOTELIGEO is given within a shorter time frame (approximately 50 days) before HSCT. Followpatients closely for early evidence of transplant-related complications.
6 ADVERSE REACTIONS
The following serious adverse reactions are discussed in greater detail in other sections of the
labeling:
Dermatologic Toxicity [see Warnings and Precautions (5.1)].
Infusion Reactions [see Warnings and Precautions (5.2)].
Infections [see Warnings and Precautions (5.3)].
Autoimmune Complications [see Warnings and Precautions (5.4)].
Complications of Allogeneic HSCT after POTELIGEO [see Warnings and Precautions (5.5)].
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 to rates in the clinical trialsof another drug and may not reflect the rates observed in practice.
Trial 1
The data described below reflect exposure to POTELIGEO in a randomized, open-label, activelycontrolled clinical trial for adult patients with MF or SS who received at least one prior systemictherapy [see Clinical Studies (14)]. Of 370 patients treated, 184 (57% with MF, 43% with SS)received POTELIGEO as randomized treatment and 186 (53% with MF, 47% with SS) receivedvorinostat. In the vorinostat arm, 135 patients (73%) subsequently crossed over to POTELIGEOfor a total of 319 patients treated with POTELIGEO.
POTELIGEO was administered at 1 mg/kg intravenously over at least 60 minutes on days 1, 8,15, and 22 of the first 28-day cycle and on days 1 and 15 of subsequent 28-day cycles.
Premedication (diphenhydramine, acetaminophen) was optional and administered to 65% ofrandomized patients for the first infusion. The comparator group received vorinostat 400 mgorally once daily, given continuously in 28-day cycles. Treatment continued until unacceptabletoxicity or progressive disease.
The median age was 64 years (range, 25 to 101 years), 58% of patients were male, 70% werewhite, and 99% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or1. Patients had a median of 3 prior systemic therapies. The trial required an absolute neutrophilcount (ANC) ≥1500/µL (≥1000/µL if bone marrow was involved), platelet count ≥100,000/µL(≥75,000/µL if bone marrow was involved), creatinine clearance >50 mL/min or serumcreatinine ≤1.5 mg/dL, and hepatic transaminases ≤2.5 times upper limi |
