Diffuse Large B-Cell Lymphoma (DLBCL)


Polivy® (polatuzumab vedotin-piiq) is an antibody-drug conjugate (ADC) designed to direct treatment at the B-cell surface antigen CD79b. It is used in combination with bendamustine and Rituxan® (rituximab) and indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, who have tried at least 2 prior therapies.1 Polivy was developed by Genentech (a subsidiary of Roche) for the treatment of hematological malignancies.2 The US Food and Drug Administration (FDA) granted accelerated approval to Polivy on June 10, 2019.3 

Mechanism of Action

Polivy is a CD79b-directed ADC with 3 components: 1) a humanized immunoglobulin G1 (igG1) monoclonal antibody against human CD79b, 2) a small molecule microtubule-disrupting antimitotic agent monomethyl auristatin E (MMAE), and 3) a protease-cleavable linker maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl (mc-vc-PAB) that covalently conjugates MMAE to the polatuzumab antibody. When this antibody binds to CD79b, which is a B-cell surface antigen, it triggers the internalization of the entire B-cell receptor (BCR), thus selectively delivering the bound antibody. After internalization, the BCR and antibody are degraded, releasing the potent MMAE cytotoxin and allowing its intracellular delivery. Polivy therefore has an action against dividing B cells. MMAE binds to microtubules and kills dividing cells by inhibiting cell division and inducing apoptosis.2,5,6

Read more about DLBCL experimental therapies

Administration

The drug is supplied as a sterile, preservative-free lyophilized powder for infusion after reconstitution and further dilution.5 The recommended dosage is 1.8 mg/kg administered as an intravenous infusion over 90 minutes every 21 days for 6 cycles, together with bendamustine and a rituximab product. This regimen can be administered in any order on the first day of each cycle, but the 21-day cycle must be maintained. If the first infusion is well tolerated, subsequent infusions of Polivy can be given over a 30-minute period.4,5 

Read more about DLBCL treatment

Adverse Effects

Common side effects seen in more than 10% of patients following the administration of Polivy include: gastrointestinal symptoms such as vomiting and diarrhea; blood and lymphatic system abnormalities such as anemia, neutropenia, thrombocytopenia, lymphopenia, and febrile neutropenia; neurological symptoms such as dizziness and peripheral neuropathy; general symptoms such as fever, fatigue, decreased appetite, and infusion reactions; infections such as pneumonia and upper respiratory infections; and metabolic and nutritional abnormalities such as hypoalbuminemia, hypokalemia, and hypocalcemia.8

Other uncommon side effects include hypophosphatemia (9%), pancytopenia (7%), elevated transaminase level (7%), arthralgia (7%), elevated lipase level (7%), and pneumonitis (4.4%).8 

Get full prescribing information for Polivy at MPR

Warnings and Precautions

Patients should be monitored for peripheral neuropathy. The dose should be modified accordingly or the drug should be discontinued.1,4

Infusion-related reactions can occur, so it’s essential to premedicate patients with antihistamines and antipyretics and provide close monitoring. If reactions occur, it is important to interrupt or discontinue infusions.1,4

Complete blood counts should be monitored for signs of myelosuppression. This should be managed using reductions or delays in doses along with growth factor support. Laboratory testing should also examine levels of liver enzymes and bilirubin to assess for signs of hepatotoxicity and be used to scan for signs of infection.1,4

Patients should be under close observation for any signs of serious and opportunistic bacterial, fungal, or viral infections.1,4

Additionally, it is important to monitor for any new or worsening behavioral, cognitive, or neurological symptoms that could indicate progressive multifocal leukoencephalopathy.1,4

Patients with a high tumor burden or rapidly proliferative tumors should be closely monitored due to the risk of tumor lysis syndrome.1,4

The drug can cause embryo-fetal toxicity. Female patients of reproductive age and their male partners are advised to use effective contraception during treatment with Polivy and for at least 3 months and 5 months after the last dose, respectively.1,4 Breastfeeding is not recommended during treatment with Polivy and for a minimum of 2 months after the last dose.1,4

Safety and Efficacy in Clinical Trials

The FDA approval of Polivy was based on complete response rates noted in the GO29365 study (NCT02257567), a randomized, open-label, multicenter controlled phase 1b/2 clinical trial.7 The trial included 80 patients with relapsed or refractory DLBCL who had tried at least 1 prior therapy. The patients received either Polivy in combination with bendamustine and rituximab (P+BR) or bendamustine and rituximab (BR) for 6 cycles of 21 days. 

The efficacy was established on the complete response (CR) rate and response duration, and it was reviewed by an independent committee. The results showed that the CR rate was 40% in patients who received P+BR compared to 18% in those receiving BR alone. The overall response rate, including complete and partial responses, was 63% with P+BR compared to 25% with BR.3,6 

Read more about DLBCL prognosis

References

  1. ​​Polivy- polatuzumab vedotin injection, powder, lyophilized, for solution. DailyMed. Updated May 13, 2020. Accessed August 19, 2022.
  2. Deeks E. Polatuzumab vedotin: first global approval. Drugs. 2019;79(13):1467-1475. doi:10.1007/s40265-019-01175-0
  3. FDA approves polatuzumab vedotin-piiq for diffuse large B-cell lymphoma. US Food and Drug Administration (FDA). June 10, 2019. Accessed August 19, 2022.
  4. Polivy. Prescribing information. Genentech, Inc; 2019. Accessed August 19, 2022.
  5. Polivy. RxList. Updated September 21, 2021. Accessed August 19, 2022.
  6. Polivy (polatuzumab vedotin-piiq). CenterWatch. Accessed August 19, 2022.
  7. A study of polatuzumab vedotin (DCDS4501A) in combination with rituximab or obinutuzumab plus bendamustine in participants with relapsed or refractory follicular or diffuse large B-cell lymphoma. ClinicalTrials.gov. October 6, 2014. Updated December 1, 2021. Accessed August 19, 2022.
  8. Shultes K. Polatuzumab vedotin-piiq (Polivy®). Oncol Times. 2020;42(4):9. doi:10.1097/01.COT.0000655948.27597.b4

Reviewed by Kyle Habet, MD, on 8/26/2022.

READ MORE ON DLBCL