POLIVY offers a predictable safety profile1

Select Grade 3 or higher adverse reactions in both study arms1

The safety of POLIVY+BR (n=45) is based on a safety run-in stage trial (n=6) and the randomized cohort (n=39) comparing treatment with BR alone in patients with R/R DBLCL.

The types of adverse events reported in Study GO29365 were consistent compared to control.

POLIVY® (polatuzumab vedotin-piiq) Grade 3-4 adverse reactions

The table includes a combination of grouped and ungrouped terms. Events were graded using NCI CTCAE version 4.9
*Includes 2 events with fatal outcome.
Includes 1 event with fatal outcome.
NCI CTCAE=National Cancer Institute Common Terminology Criteria for Adverse Events.

The adverse drug reactions (all grades; >10% incidence and ≥5% more for all grades in the POLIVY+BR arm) occurring in patients with R/R DLBCL treated with POLIVY+BR or BR were neutropenia (49% vs 44%), thrombocytopenia (49% vs 33%), anemia (47% vs 28%), peripheral neuropathy (40% vs 8%), diarrhea (38% vs 28%), pyrexia (33% vs 23%), decreased appetite (27% vs 21%), pneumonia (22% vs 15%), vomiting (18% vs 13%), infusion-related reaction (18% vs 8%), weight decreased (16% vs 8%), hypokalemia (16% vs 10%), hypoalbuminemia (13% vs 8%), upper respiratory tract infection (13% vs 8%), dizziness (13% vs 8%), lymphopenia (13% vs 8%), and hypocalcemia (11% vs 5%).

Other clinically relevant adverse reactions (<10% or with a <5% difference) in recipients of POLIVY+BR included blood and lymphatic system disorders: pancytopenia (7%); musculoskeletal disorders: arthralgia (7%); investigations: hypophosphatemia (9%), transaminase elevation (7%), lipase increase (7%); and respiratory disorders: pneumonitis (4.4%). 

  • Fatal adverse reactions occurred in 7% in the POLIVY+BR arm within 90 days of last treatment
  • Serious adverse reactions occurred in 64%, most often from infection
  • Serious adverse reactions in ≥5% of recipients of POLIVY+BR included pneumonia (16%), febrile neutropenia (11%), pyrexia (9%), and sepsis (7%)
 

The safety of POLIVY (polatuzumab vedotin-piiq) was also evaluated in an expanded patient population1

Study GO29365 expanded safety data

Safety was also evaluated in 173 patients with R/R lymphoma who received POLIVY, bendamustine, and either a rituximab product or obinutuzumab (POLIVY and chemoimmunotherapy), including the 45 patients with DLBCL.

Common Adverse Reactions (≥20% Any Grade and ≥5% Grade 3 or Higher) in Patients Receiving POLIVY + Chemoimmunotherapy for R/R Lymphoma

POLIVY® (polatuzumab vedotin-piiq) all grades and ≥3 grade adverse reactions

The table includes a combination of grouped and ungrouped terms.
Primary prophylaxis with granulocyte colony-stimulating factor was given to 46% of all patients.
§Includes 5 events with fatal outcome.
||Includes 4 events with fatal outcome.

Other clinically relevant adverse reactions (<20% any grade) included infusion-related reaction (7%), upper respiratory tract infection (16%), lower respiratory tract infection (10%), herpesvirus infection (12%), cytomegalovirus infection (1.2%), dyspnea (19%), pneumonitis (1.7%), dizziness (10%), weight decrease (10%), transaminase elevation (8%), lipase increase (3.5%), arthralgia (7%), and blurred vision (1.2%).

  • Fatal adverse reactions occurred in 4.6% of recipients of POLIVY within 90 days of last treatment, with infection as a leading cause
  • Serious adverse reactions occurred in 60% of patients, most often from infection

Changes in laboratory values were comparable to BR1

Selected Laboratory Abnormalities Worsening From Baseline in Patients With R/R DLBCL Receiving POLIVY+BR and ≥5% Greater in the POLIVY+BR Arm1

POLIVY® (polatuzumab vedotin-piiq) selected worsening laboratory abnormalities

Includes laboratory abnormalities that are new or worsening in grade or with worsening from baseline unknown.

Effects of other drugs on POLIVY1

Strong CYP3A inhibitors

  • Concomitant use with a strong CYP3A4 inhibitor may increase unconjugated MMAE AUC, which may increase POLIVY toxicities. Monitor patients for signs of toxicity

Strong CYP3A inducers

  • Concomitant use with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC

SGPT=serum glutamic-pyruvic transaminase; ALT=alanine aminotransferase; SGOT=serum glutamic-oxaloacetic transaminase; AST=aspartate aminotransferase; CYP3A=cytochrome P450 family 3 subfamily A; MMAE=monomethyl auristatin E; AUC=area under the concentration-time curve.

Completion of therapy with POLIVY+BR vs BR:
percentage of patients who received 6 cycles1

Completion of therapy with POLIVY+BR vs BR

The lower completion rates in the BR arm were primarily due to a higher rate of treatment discontinuation owing to disease progression.3

  • Disease progression resulted in treatment discontinuation in 15.4% of patients treated with POLIVY+BR vs 53.8% of patients treated with BR3
  • Treatment discontinuations of any study drug due to adverse events were more frequent with POLIVY+BR vs BR (33.3% vs 10.3%, respectively)3
  • The most common adverse reactions leading to treatment discontinuation were thrombocytopenia and/or neutropenia in patients treated with POLIVY+BR1
  • In patients receiving POLIVY+BR, adverse reactions leading to dose reduction occurred in 18%, dose interruption in 51%, and permanent discontinuation of all treatment in 33.3%1,3

Please see Dose Modifications and full Prescribing Information for recommendations on managing select adverse events.

Indication

POLIVY in combination with bendamustine and a rituximab product is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, after at least 2 prior therapies.

Accelerated approval was granted for this indication based on complete response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Peripheral Neuropathy
POLIVY can cause severe peripheral neuropathy. Peripheral neuropathy occurs as early as the first cycle of treatment and is cumulative. POLIVY may exacerbate preexisting peripheral neuropathy.

In Study GO29365, of 173 patients treated with POLIVY, 40% reported new or worsening peripheral neuropathy, with a median time to onset of 2.1 months. The peripheral neuropathy was Grade 1 in 26% of cases, Grade 2 in 12%, and Grade 3 in 2.3%. Peripheral neuropathy resulted in POLIVY dose reduction in 3% of treated patients, dose delay in 1.2%, and permanent discontinuation in 2.9%. Sixty-five percent of patients reported improvement or resolution of peripheral neuropathy, after a median time to resolution of 1 month, and 48% reported complete resolution.

The peripheral neuropathy is predominantly sensory; however, motor and sensorimotor peripheral neuropathy also occur. Monitor for symptoms of peripheral neuropathy such as hypoesthesia, hyperesthesia, paresthesia, dysesthesia, neuropathic pain, burning sensation, weakness, or gait disturbance. Patients experiencing new or worsening peripheral neuropathy may require a delay, dose reduction, or discontinuation of POLIVY.

Infusion-Related Reactions
POLIVY can cause severe infusion reactions. Delayed infusion-related reactions as late as 24 hours after receiving POLIVY have occurred. With premedication, 7% of patients (12/173) in Study GO29365 reported infusion-related reactions after the administration of POLIVY. The reactions were Grade 1 in 67% of patients, Grade 2 in 25%, and Grade 3 in 8%. Symptoms included fever, chills, flushing, dyspnea, hypotension, facial swelling, and urticaria.

Administer an antihistamine and an antipyretic prior to the administration of POLIVY, and monitor patients closely throughout the infusion. If an infusion-related reaction occurs, interrupt the infusion and institute appropriate medical management.

Myelosuppression
Treatment with POLIVY can cause serious or severe myelosuppression, including neutropenia, thrombocytopenia, and anemia. In patients treated with POLIVY plus bendamustine and a rituximab product (BR) (n=45), 42% received primary prophylaxis with granulocyte colony-stimulating factor. Grade 3 or higher hematologic adverse reactions included neutropenia (42%), thrombocytopenia (40%), anemia (24%), lymphopenia (13%), and febrile neutropenia (11%). Grade 4 hematologic adverse reactions included neutropenia (24%), thrombocytopenia (16%), lymphopenia (9%), and febrile neutropenia (4.4%). Cytopenias were the most common reason for treatment discontinuation (18% of all patients).

Monitor complete blood counts throughout treatment. Cytopenias may require a delay, dose reduction, or discontinuation of POLIVY. Consider prophylactic granulocyte colony-stimulating factor administration.

Serious and Opportunistic Infections
Fatal and/or serious infections, including opportunistic infections such as sepsis, pneumonia (including Pneumocystis jiroveci and other fungal pneumonia), herpesvirus infection, and cytomegalovirus infection, have occurred in patients treated with POLIVY.

Grade 3 or higher infections occurred in 32% (55/173) of patients treated with POLIVY. Infection-related deaths were reported in 2.9% of patients within 90 days of last treatment.

Closely monitor patients during treatment for signs of infection. Administer prophylaxis for Pneumocystis jiroveci pneumonia and herpesvirus.

Progressive Multifocal Leukoencephalopathy (PML)
PML has been reported after treatment with POLIVY (0.6%, 1/173). Monitor for new or worsening neurological, cognitive, or behavioral changes. Hold POLIVY and any concomitant chemotherapy if PML is suspected, and permanently discontinue if the diagnosis is confirmed.

Tumor Lysis Syndrome
POLIVY may cause tumor lysis syndrome. Patients with high tumor burden and rapidly proliferating tumors may be at increased risk of tumor lysis syndrome. Monitor closely and take appropriate measures, including tumor lysis syndrome prophylaxis.

Hepatotoxicity
Serious cases of hepatotoxicity that were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, have occurred in patients treated with POLIVY.

In recipients of POLIVY in Study GO29365 (n=173), Grade 3 and 4 transaminase elevations of AST and/or ALT developed in 1.9% and 1.9%, respectively. Laboratory values suggestive of drug-induced liver injury (both an ALT or AST greater than 3 times upper limit of normal [ULN] and total bilirubin greater than 2 times ULN) occurred in 2.3% of patients.

Preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may increase the risk of hepatotoxicity. Monitor liver enzymes and bilirubin level.

Embryo-Fetal Toxicity
Based on the mechanism of action and findings from animal studies, POLIVY can cause fetal harm when administered to a pregnant woman. When administered to rats, the small molecule component of POLIVY, monomethyl auristatin E, caused adverse developmental outcomes, including embryo-fetal mortality and structural abnormalities, at exposures below those occurring clinically at the recommended dose.

Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with POLIVY and for at least 3 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with POLIVY and for at least 5 months after the last dose.

The Most Common Adverse Reactions
The most common adverse reactions (≥20%) included neutropenia, thrombocytopenia, anemia, peripheral neuropathy, fatigue, diarrhea, pyrexia, decreased appetite, and pneumonia.

Lactation
Advise women not to breastfeed during treatment with POLIVY and for at least 2 months after the last dose.

You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.

Please see the full Prescribing Information for additional Important Safety Information.

    • POLIVY Prescribing Information. South San Francisco, CA: Genentech, Inc.; September 2020.

      POLIVY Prescribing Information. South San Francisco, CA: Genentech, Inc.; September 2020.

    • Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-Cell Lymphomas V.2.2020. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed January 27, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org.

      Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-Cell Lymphomas V.2.2020. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed January 27, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org.

    • Sehn LH, Herrera AF, Flowers CR, et al. Polatuzumab vedotin in relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol. 2020;38(2):155-165.

      Sehn LH, Herrera AF, Flowers CR, et al. Polatuzumab vedotin in relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol. 2020;38(2):155-165.

    • Data on File. South San Francisco, CA: Genentech, Inc. 2018.

      Data on File. South San Francisco, CA: Genentech, Inc. 2018.

    • D’Arena G, Musto P, Cascavilla N, Dell’Olio M, Di Renzo N, Carotenuto M. Quantitative flow cytometry for the differential diagnosis of leukemic B-cell chronic lymphoproliferative disorders. Am J Hematol. 2000;64(4):275-281.

      D’Arena G, Musto P, Cascavilla N, Dell’Olio M, Di Renzo N, Carotenuto M. Quantitative flow cytometry for the differential diagnosis of leukemic B-cell chronic lymphoproliferative disorders. Am J Hematol. 2000;64(4):275-281.

    • Dornan D, Bennett F, Chen Y, et al. Therapeutic potential of an anti-CD79b antibody-drug conjugate, anti-CD79b-vc-MMAE, for the treatment of non-Hodgkin lymphoma. Blood. 2009;114(13):2721-2729.

      Dornan D, Bennett F, Chen Y, et al. Therapeutic potential of an anti-CD79b antibody-drug conjugate, anti-CD79b-vc-MMAE, for the treatment of non-Hodgkin lymphoma. Blood. 2009;114(13):2721-2729.

    • Friedberg JW. Relapsed/refractory diffuse large B-cell lymphoma. Hematology Am Soc Hematol Educ Program. 2011;2011(1):498-505.

      Friedberg JW. Relapsed/refractory diffuse large B-cell lymphoma. Hematology Am Soc Hematol Educ Program. 2011;2011(1):498-505.

    • Crump M, Neelapu SS, Farooq U, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017;130(16):1800-1808.

      Crump M, Neelapu SS, Farooq U, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017;130(16):1800-1808.

    • National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) V4. 2009.
      https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf. Accessed December 4, 2019.

      National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) V4. 2009.
      https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf. Accessed December 4, 2019.