Polivy Adverse Reactions

Clinical Trials: Summary of the safety profile: For the clinical development program of Polivy as a whole, an estimated total of 1429 patients have received Polivy. The adverse drug reactions (ADRs) described in this section were identified during treatment and follow-up of previously treated diffuse large B-cell lymphoma (DLBCL) patients (n=151) from the pivotal clinical trial GO29365. This includes run-in phase patients (n=6) and randomized patients (n=39), and extension cohort patients (n=106) who received Polivy in combination with bendamustine and rituximab (BR) compared to randomized patients (n=39) who received BR alone. Patients in the Polivy treatment arm received a median of 5 cycles of treatment while randomized patients in the comparator arm received a median of 3 cycles of treatment.
The most frequently-reported (≥30%) ADRs in patients treated with Polivy in combination with BR were anemia (46.7%), thrombocytopenia (46.7%), neutropenia (46.7%), diarrhea (37.8%), nausea (33.3%) and peripheral neuropathy. Serious adverse events were reported in 55.6% of Polivy plus BR treated patients which included the following that occurred in >5% of patients: febrile neutropenia (9.3%), pyrexia (7.9%), pneumonia (6.6%), and sepsis (6.6%).
The ADR leading to treatment regimen discontinuation in >5% of patients was thrombocytopenia (6.0%).
Tabulated list of ADRs from clinical trials: The ADRs are listed as follows 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 < 1/1000), very rare (< 1/10,000). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness. (See Table 6.)

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Description of selected adverse drug reactions from clinical trials: In the Polivy plus BR arm, Grade 3 or higher neutropenia, thrombocytopenia, and anaemia were reported in 40%, 37.8%, and 24.4% of patients, respectively.
Myelosuppression: 4.0% of patients in the Polivy plus BR arm discontinued Polivy due to neutropenia compared to 2.6% of patients in the BR arm who discontinued treatment due to neutropenia. Thrombocytopenia events led to discontinuation of treatment in 7.9% of patients in the Polivy plus BR arms and 5.1% of patients in the BR arm. No patients discontinued treatment due to anemia in either the Polivy plus BR arms or BR arm.
Peripheral Neuropathy (PN): In the Polivy plus BR arms, Grade 1 and 2 PN events were reported in 15.9% and 12.6% of patients, respectively. In the BR arm, Grade 1 and 2 PN events were reported in 2.6% and 5.1% of patients, respectively. One Grade 3 PN event was reported in the Polivy plus BR arms and no Grade 3 PN events were reported in the BR arm. No Grade 4-5 PN events were reported in either the Polivy plus BR arm or BR arm. 2.6% of patients discontinued Polivy treatment due to PN and 2.0% of patients had Polivy dose reduction due to PN. No patients in the BR arm discontinued treatment or had dose reductions due to PN. In the Polivy plus BR arm, the median onset to first event of PN was 1.6 months, and 39.1% of patients with PN events reported event resolution.
Infections: Infections, including pneumonia and other types of infections, were reported in 48.3% of patients in the Polivy plus BR arms and 51.3% of patients in the BR arm. In the Polivy plus BR arms, serious infections were reported in 27.2% of patients and fatal infections were reported in 6.6% of patients. In the BR arm, serious infections were reported in 30.8% of patients and fatal infections were reported in 10.3% of patients. Four patients (2.6%) in the Polivy plus BR arms discontinued treatment due to infection compared to 2 patients (5.1%) of patients in the BR arm.
Progressive Multifocal Leukoencephalopathy (PML): One case of PML, which was fatal, occurred in one patient treated with Polivy plus bendamustine and obinutuzumab. This patient had three prior lines of therapy that included anti-CD20 antibodies.
Hepatic toxicity: In another study, two cases of serious hepatic toxicity (hepatocellular injury and hepatic steatosis) were reported and were reversible.
Gastrointestinal Toxicity: Gastrointestinal toxicity events were reported in 72.8% of patients in the Polivy plus BR arms compared to 66.7% of patients in the BR arm. Most events were Grade 1-2, and Grade 3-4 events were reported in 16.5% of patients in the Polivy plus BR arms compared to 12.9% of patients in the BR arm. The most common gastrointestinal toxicity events were diarrhea and nausea.
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system.