What is polatuzumab vedotin?
Polatuzumab vedotin-piiq is a first-in-class CD79b-directed antibody-drug conjugate with activity against dividing B cells. It consists of the monoclonal antibody against CD79b, a small-molecule antimitotic agent, MMAE, and a protease-cleavable linker that covalently connects MMAE to the monoclonal antibody.
Polatuzumab vedotin binds to CD79b, a cell-surface protein on B cells, and is internalized. Then, the linker is cleaved by lysosomal proteases, which allows for the delivery of MMAE. MMAE then binds to microtubules inhibiting cell division and induces apoptosis.
What is this approved for?
Polatuzumab vedotin is approved for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, in combination with bendamustine and rituximab, after at least two prior lines of therapy. It was granted accelerated approval based upon complete response rate and continued approval will be contingent on verification and description of clinical benefit in confirmatory trials.
Polatuzumab vedotin was approved based on the results of Study GO29365, an open-label, phase Ib/II, multi-center clinical trial in relapsed or refractory DLBCL after at least one prior line of therapy. In the phase II cohort, 80 patients were randomized 1:1 to either polatuzumab vedotin IV 1.8 mg/kg in combination with bendamustine IV (90 mg/m2) and a rituximab IV (375 mg/m2) product (P+BR) or BR alone every 21 days for 6 cycles. Randomization was stratified by duration of response (DOR) to last therapy. Patients with grade 2 or higher peripheral neuropathy, eligibility for autologous stem cell transplant (SCT), prior allogeneic SCT, active CNS disease, or transformed lymphomas were not eligible. The primary endpoint was complete response (CR) rate and response duration by independent review committee.
CR rate was higher with the P+BR arm, 40 percent (16 patients) compared to 18 percent (7 patients) with BR (p = 0.026). Overall response rate was 63 percent in the P+BR arm compared to 25 percent in the BR cohort. Seven patients in the P+BR arm (18%) had ongoing DOR of greater than 20 months (range > 20 to >= 22.5 months). Although exploratory, the progression-free survival and overall survival were longer in the P+BR arm. No correlation between CD79b expression and response was noted (J Clin Oncol 2019;38:155-165).
How do you administer this drug?
Polatuzumab vedotin is an IV infusion with a low-protein binding in-line or add-on filter (0.2-0.22-micron pore size). It is given at a dose of 1.8 mg/kg over 90 minutes for the initial dose on day 1 of a 21-day cycle. If tolerated, subsequent doses may be given over 30 minutes.
Patients should receive an antihistamine and antipyretic at least 30-60 minutes prior to the dose of drug.
What are the common side effects (> or =10%)?
* GI: diarrhea, vomiting
* Blood and lymphatic system disorders: neutropenia, thrombocytopenia, anemia, febrile neutropenia, lymphopenia
* Nervous system disorder: peripheral neuropathy, dizziness
* General: fatigue, pyrexia, infusion reaction, decreased appetite
* Infections: pneumonia, upper respiratory infection
* Metabolic and nutritional: hypokalemia, hypoalbuminemia, hypocalcemia
What are the uncommon side effects?
Additional side effects include hypophosphatemia (9%), pancytopenia (7%), transaminase elevation (7%), arthralgia (7%), lipase elevation (7%), and pneumonitis (4.4%).
Are there any important drug interactions?
Concurrent use of strong CYP3A4 inhibitors or inducers with polatuzumab vedotin-piiq should be used cautiously due to increased exposure to MMAE AUC resulting in toxicity or decreased exposure of MMAE AUC.
How do I adjust the dose in the setting of renal or hepatic insufficiency?
Polatuzumab vedotin should be avoided in patients with moderate-to-severe hepatic impairment due to likely increased exposure to MMAE. No adjustments are necessary for mild hepatic impairment or renal impairment.
Practical tips
* Treatment should be held until ANC recovers to greater than 1,000/microliter or platelets recover to greater than 75,000/microliter. Dose reductions may be required based on time of recovery.
* Peripheral neuropathy was predominantly sensory with a median onset of 2.1 months.
* Polatuzumab vedotin-piiq can cause embryo-fetal harm to pregnant women. Effective contraception should be utilized during treatment and for 3 months after final dose for females and at least 5 months for males.
What should patients know about polatuzumab vedotin?
Patients should contact their health care provider if they experience:
* New or worsening numbness or tingling in hands/feet, muscle weakness
* Infusion reaction symptoms (fever, chills, rash, or breathing problems within 24 hours of infusion)
* Bleeding
* Signs of infection (fever, chills, cough, painful urination)
What else should I know about this drug?
* Patients should receive prophylaxis against herpes virus as well as Pneumocystis jiroveci pneumonia during treatment.
* Administer tumor lysis prophylaxis in patients at higher risk for tumor lysis syndrome.
* Consider use of prophylactic granulocyte colony-stimulating factors for neutropenia. Primary prophylaxis was utilized in 46 percent of patients in clinical trials.
What useful links are available for more info?
* FDA Approval Announcement: https://bit.ly/2RyX2oh
* Highlights of Prescribing Information: https://bit.ly/318UJLS
Any ongoing clinical trials for this drug?
Clinical trials with polatuzumab vedotin are being conducted to investigate therapy in follicular lymphoma, DLBCL, and chronic lymphocytic leukemia. It is being studied in combination with agents such as gemcitabine, cyclophosphamide, doxorubicin, prednisone (CHP), venetoclax, lenalidomide, and atezolizumab. Find more info at https://clinicaltrials.gov.
KENDALL C. SHULTES, PHARMD, BCOP, is Assistant Professor at Belmont University College of Pharmacy and Clinical Pharmacy Specialist at Vanderbilt-Ingram Cancer Center Cool Springs, Nashville, Tenn. JANELLE E. MANN, PHARMD, BCOP, is the Manager of Clinical Pharmacy Services and practices as an Ambulatory Clinical Oncology Pharmacist, Washington University School of Medicine, Alvin J. Siteman Cancer Center, St. Louis, Mo., She serves as the Pharmacy Forum column editor. RAMASWAMY GOVINDAN, MD, Professor of Medicine; Anheuser Busch Chair in Medical Oncology; Director, Section of Medical Oncology, Division of Oncology, Washington University School of Medicine, serves as the Pharmacy Forum column physician advisor.