Polivy

Generic name: Polatuzumab

Trade name: Polivy

Full names: Polatuzumab, Polatuzumab vedotin-piiq, Polivy

Indications:

POLIVY is used in combination with the chemotherapy drugs bendamustine and rituximab products (referred to as the "BR" combination) to treat adult patients with diffuse large B-cell lymphoma (DLBCL), which occurs in patients who have received at least two prior treatments but have worsened or relapsed.

Usage and Dosage:

The recommended dose of POLIVY is 1.8 mg/kg intravenously every 21 days, combined with bendamustine and rituximab products for 6 cycles. On the first day of each cycle, use POLIVY, bendamustine, and rituximab in any order. When used together, the recommended dose of bendamustine is 90 mg/m²/day on the first and second days of each cycle. The recommended dose of rituximab is 375 mg/m² intravenously on the first day of each cycle. If the previous infusion is tolerated, subsequent infusions may be given within 30 minutes.

If not premedicated, antihistamines and antipyretics should be taken at least 30 minutes before POLIVY. The initial dose of POLIVY should be given over 90 minutes. Monitor patients for infusion-related reactions during the infusion and for at least 90 minutes after completion of the initial dose. If the previous infusion is well tolerated, subsequent doses of POLIVY may be administered as a 30-minute infusion, and the patient should be monitored during and for at least 30 minutes after the infusion.

Adverse reactions:

>10%:

Central nervous system: peripheral neuropathy (40%; grade 3: 2%), dizziness (13%)

Endocrine and metabolic: decreased blood calcium (44%), hypokalemia (16%), weight loss (16%), hypoalbuminemia (13%) ), hypocalcemia (11%)

Gastrointestinal tract: diarrhea (38%), elevated serum lipase (7%-36%), decreased appetite (27%), elevated serum amylase (24%), vomiting (18%)

Hematology and tumors: neutropenia (49%; grade ≥3: 42%; grade 4: 13%-24%), hematuria Thrombocytopenia (49%; grade ≥3: 40%; grade 4: 11%-16%), anemia (47%; grade ≥3: 24%), lymphopenia (13%, grade ≥3: 13%; grade 4: 9%), febrile neutropenia (11%; grade ≥3: 11%; grade 4: 4%)

Liver: elevated serum alanine aminotransferase (3%) 8%), elevated serum aspartate aminotransferase (36%)

Kidney: elevated serum creatinine (87%)

Respiratory tract: pneumonia (16%-22%; including fungal pneumonia), upper respiratory tract infection (13%)

Others: fever (9%-33%), infusion-related reactions (18%)

1% - 10%:

Endocrinology and metabolism: hypophosphatemia (9%)

Hematology and neoplasms: pancytopenia (7%)

Liver: elevated serum aminotransferases (7%), hepatotoxicity (2%)

Immune system: antibody development (3%-6%)

Infections: sepsis (7%)

Neuromuscular and skeletal: joint pain (7%)< /p>

Respiratory: Pneumonia (4%)

<1%:

Progressive multifocal leukoencephalopathy

Undefined frequency:

Liver: Elevated serum bilirubin

Infections: Cytomegalovirus disease, herpes virus infection

Respiratory: Pneumocystis pneumonia

Contraindications:

None.

Note:

Peripheral neuropathy: POLIVY can cause peripheral neuropathy, even severe cases. Peripheral neuropathy appears as early as the first cycle of treatment and is a cumulative effect. POLIVY may aggravate existing peripheral neuropathy. Peripheral neuropathy is predominantly sensory; however, motor and sensorimotor peripheral neuropathy can also occur. Monitor for symptoms of peripheral neuropathy such as hypoesthesia, hyperesthesia, paresthesias, paresthesia, neuralgia, burning, weakness, or gait disturbance. Patients who develop new or worsening peripheral neuropathy may need to delay, reduce dose, or discontinue POLIVY.

Infusion-related reactions: include symptoms such as fever, chills, rash, or breathing problems. Pre-treat with antihistamines and antipyretics. Monitor the patient closely throughout the infusion period and interrupt or stop infusion reactions.

Myelosuppression: Treatment with POLIVY can result in severe or severe myelosuppression, including neutropenia, thrombocytopenia, and anemia. Monitor complete blood count. Manage with dose delay or reduction and growth factor support. Monitor for signs of infection.

Serious and opportunistic infections: Fatal or serious infections have occurred, including opportunistic infections such as sepsis, pneumonia (including pneumocystis and other fungal pneumonias), herpes virus infections, and cytomegalovirus infections. Patients should be closely monitored for signs of bacterial, fungal, or viral infection; prophylaxis for Pneumocystis pneumonia and herpes viruses should be administered.

Progressive Multifocal Leukoencephalopathy (PML): Monitor patients for prophylaxis of new or worsening neurological, cognitive, or behavioral changes in PML.

Tumor lysis syndrome: Can cause tumor lysis syndrome. Patients with high tumor burden and rapid tumor proliferation are at increased risk of developing tumor lysis syndrome. Closely monitor patients with high tumor burden or rapidly proliferating tumors; including tumor lysis syndrome prophylaxis.

Hepatotoxicity: Predict that presence of liver disease, elevated baseline liver enzymes, and concomitant drug therapy may increase the risk of hepatotoxicity; monitor liver enzymes and bilirubin.

Embryo-fetal toxicity: May cause fetal harm. Advise females of reproductive potential with potential risk to the fetus and to refrain from breastfeeding during treatment and for at least 2 months after the last dose.

Storage:

Refrigerate at 2°C to 8°C (36°F to 46°F). Do not freeze or shake.

Mechanism of action:

POLIVY is a CD79b-directed antibody-drug conjugate with anti-B cell activity. Small molecule MMAE is an antimitotic agent covalently linked to an antibody through a cleavable linker. The monoclonal antibody binds to CD79b, a B cell-specific surface protein that is a component of the B cell receptor. Upon binding to CD79b, polatuzumabvedotin-piiq is internalized and the linker is cleaved by lysosomal proteases to enable intracellular delivery of MMAE. MMAE binds to microtubules and kills dividing cells by inhibiting cell division and inducing apoptosis.

Safety and efficacy:

Polivy is the first chemoimmunotherapy approved to treat R/R DLBCL. Compared with commonly used treatment options, Polivy can significantly improve the clinical outcomes of patients.

Polivy’s positive Phase 1b/2 trial results finally gave it the regulatory green light. The trial results showed that the combination was more effective than the commonly used treatment regimen of bendamustine and Rituxan. In that trial, 40% of patients achieved a complete response with the Polivy combination, compared with just 18% of patients in the bendamustine and Rituxan group. At the end of the treatment course, 45% of patients in the Polivy combination achieved an objective response, compared with only 18% in the bendamustine and Rituxan group.