Polivy

Polivy must only be administered under the supervision of a healthcare professional experienced in the diagnosis and treatment of cancer patients. 8 mg/kg, given as an intravenous infusion every 21 days in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) for 6 cycles.

Polivy, rituximab, cyclophosphamide and doxorubicin can be administered in any order on Day 1 after the administration of prednisone. Prednisone is administered on Days 1-5 of each cycle. Cycles 7 and 8 consist of rituximab as monotherapy.

Refer to the summary of product characteristics (SmPC) of chemotherapy agents given in combination with Polivy for patients with previously untreated DLBCL. 8 mg/kg, given as an intravenous infusion every 21 days in combination with bendamustine and rituximab for 6 cycles.

Polivy, bendamustine and rituximab can be administered in any order on Day 1 of each cycle. When administered with Polivy, the recommended dose of bendamustine is 90 mg/m2/day on Day 1 and Day 2 of each cycle and the recommended dose of rituximab is 375 mg/m2 on Day 1 of each cycle.

8 mg/kg Polivy at a total dose 240 mg, it is recommended not to exceed the dose 240 mg/cycle. Previously untreated and relapsed or refractory patients If not already premedicated, premedication with an antihistamine and anti-pyretic should be administered to patients prior to Polivy.

Delayed or missed doses If a planned dose of Polivy is missed, it should be administered as soon as possible and the schedule of administration should be adjusted to maintain a 21-day interval between doses. Dose modifications The infusion rate of Polivy should be slowed or interrupted if the patient develops an infusion-related reaction.

Polivy should be discontinued immediately and permanently if the patient experiences a life-threatening reaction. There are different potential dose modifications for Polivy in patients with previously untreated DLBCL and those who are relapsed or refractory.

4) see Table 1 below. 4 mg/kg. 0 mg/kg. 0 mg/kg and Grade 2 occurs at Day 1 of a future cycle, discontinue Polivy. Motor neuropathy:  Withhold Polivy dosing until improvement to Grade ≤1. 4 mg/kg. 4 mg/kg and Grade 2 occurs at Day 1 of a future cycle, withhold Polivy dosing until improvement to Grade ≤ 1.

Summary of the safety profile 11 The safety of Polivy has been evaluated in 435 patients in Study GO39942 (POLARIX). 8 were identified:  during treatment and follow-up of previously untreated DLBCL patients from the pivotal clinical trial GO39942 (POLARIX), who received Polivy plus R-CHP (n=435) or R-CHOP (n=438).

5% of patients who received 6 cycles of vincristine in the R-CHOP group. 8%). 1% of Polivy plus R-CHP treated patients. 3%). 1%). The safety of Polivy has been evaluated in 151 patients in Study GO29365. 8 were identified:  during treatment and follow-up of previously treated DLBCL patients (n=151) from the pivotal clinical trial GO29365.

This includes run-in phase patients (n=6), randomized patients (n=39), and extension cohort patients (n=106) who received Polivy plus BR compared to randomized patients (n=39) who received BR alone. Patients in the treatment arms received a median of 5 cycles of treatment while randomized patients in the comparator arm received a median of 3 cycles of treatment.

5%). 7% of Polivy plus BR treated patients. 9%). 9%). Tabulated list of ADRs from clinical trials The ADRs in 586 patients treated with Polivy are presented in Table 4. The ADRs are listed below by MedDRA system organ class (SOC) and categories of frequency.

The corresponding frequency category for each adverse drug reaction is based on the following convention: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000).

Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness. Table 4 Tabulated list of ADRs in patients treated with Polivy in clinical trials Infections and infestations Very common pneumoniaa, upper respiratory tract infection Common sepsisa, herpes virus infectiona, cytomegalovirus infection, urinary tract infectionc Blood and lymphatic system disorders Very common febrile neutropenia, neutropenia, thrombocytopenia, anaemia, leukopenia 12 Common lymphopenia, pancytopenia Metabolism and nutrition disorders Very common hypokalaemia, decreased appetite Common hypocalcaemia, hypoalbuminemia Nervous system disorders Very common neuropathy peripheral Common dizziness Eye disorders Uncommon vision blurredb Respiratory, thoracic and mediastinal disorders Very common cough Common pneumonitis, dyspnoeac Gastrointestinal disorders Very common diarrhoea, nausea, constipation, vomiting, mucositisc, abdominal pain Skin and subcutaneous tissue disorders Very common alopeciac Common pruritus, skin infectionsc, rashc, dry skinc Musculoskeletal disorders Common arthralgia, myalgiac General disorders and administration site conditions Very common pyrexia, fatigue, asthenia Common peripheral edemac, chills Uncommon infusion site extravasation Investigations Very common weight decreased Common lipase increaseb, hypophosphataemia Hepatobiliary disorders Common transaminases increased Injury, poisoning and procedural complications Very Common infusion related reaction a ADR associated with fatal outcome b ADRs observed in relapsed or refractory DLBCL only.

Traceability In order to improve traceability of biological medicinal products, the trade name and the batch number of the administered product should be clearly recorded. Myelosuppression Serious and severe neutropenia and febrile neutropenia have been reported in patients treated with Polivy as early as the first cycle of treatment.

Prophylactic granulocyte colony stimulating factor (G-CSF) administration was required in the clinical development and should be considered. Grade 3 or 4 thrombocytopenia or anaemia can also occur with Polivy. Complete blood counts should be monitored prior to each dose of Polivy.

2). Peripheral neuropathy (PN) PN has been reported in patients treated with Polivy as early as the first cycle of treatment, and the risk increases with sequential doses. Patients with pre-existing PN may experience worsening of this condition.

PN reported with treatment with Polivy is predominantly sensory PN. However, motor and sensorimotor PN have also been reported. Patients should be monitored for symptoms of PN such as hypoesthesia, hyperesthesia, paraesthesia, dysesthesia, neuropathic pain, burning sensation, muscle weakness, or gait disturbance.

2). 8). Reactivation of latent infections has been reported. Patients should be closely monitored during treatment for signs of bacterial, fungal, or viral infections and seek medical advice if signs and 8 symptoms appear. Anti-infective prophylaxis should be considered throughout treatment with Polivy.

Polivy should not be administered in the presence of an active severe infection. Polivy and any concomitant chemotherapy should be discontinued in patients who develop serious infections. Human Immunodeficiency Virus (HIV) Polivy has not been evaluated in patients with HIV.

With regard to co-administration of CYP3A-inhibitors see section

1. 4).