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POLIVY Side Effects
Lab Abnormalities
Effects of Other Drugs

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 DLBCL.

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

 

Adverse Reaction by Body System POLIVY+BR (n=45)
Grade ≥3 (%)		 BR (n=39)
Grade ≥3 (%)
Blood and lymphatic system disorders Neutropenia 42 36
  Thrombocytopenia 40 26
  Anemia 24 18
  Lymphopenia 13 8
Nervous system disorders Peripheral neuropathy 0 0
  Dizziness 0 0
Gastrointestinal disorders Diarrhea 4.4 5
  Vomiting 2.2 0
General disorders Infusion-related reaction 2.2 0
  Pyrexia 2.2 0
  Decreased appetite 2.2 0
Infections Pneumonia 16* 2.6†
  Upper respiratory tract infection 0 0
Investigations Weight decreased 2.2 2.6
Metabolism and nutrition disorders Hypokalemia 9 2.6
  Hypoalbuminemia 2.2 0
  Hypocalcemia 2.2 0

The table includes a combination of grouped and ungrouped terms. Events were graded using NCI CTCAE version 4.
*Includes 2 fatalities.
†Includes 1 fatality.


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) in an expanded patient population for Study G029365

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

Adverse Reaction by Body System POLIVY + Bendamustine + Rituximab Product or Obinutuzumab (n=173)
All Grades (%) Grade ≥3 (%)
Blood and lymphatic system disorders Neutropenia 44 39
  Thrombocytopenia 31 23
  Anemia 28 14
  Febrile neutropenia‡ 13 13
  Leukopenia 13 8
  Lymphopenia 12 12
Nervous system disorders Peripheral neuropathy 40 2.3
Gastrointestinal disorders Diarrhea 45 8
  Vomiting 27 2.9
General disorders Fatigue 40 5
  Pyrexia 30 2.9
  Decreased appetite 29 1.7
Infections Pneumonia 13 10§
  Sepsis 6 6||
Metabolism and nutrition disorders Hypokalemia 18 6

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 fatalities.
||Includes 4 fatalities.

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

Laboratory Parameter POLIVY+BR (n=45) BR (n=39)
All Grades (%) Grades 3-4 (%) All Grades (%) Grades 3-4 (%)
Hematologic
Lymphocyte count decreased 87 87 90 82
Neutrophil count decreased 78 61 56 33
Hemoglobin decreased 78 18 62 10
Platelet count decreased 76 31 64 26
Chemistry
Creatinine increased 87 4.4 77 5
Calcium decreased 44 9 26 0
SGPT/ALT increased 38 0 8 2.6
SGOT/AST increased 36 0 26 2.6
Lipase increased 36 9 13 5
Phosphorus decreased 33 7 28 8
Amylase increased 24 0 18 2.6
Potassium decreased 24 11 28 5

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

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

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

Completion of therapy graphic

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
Infusion bag icon

See Dose Modifications for recommendations on managing adverse events 

 

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NEXT: Important Safety Information
Important Safety Information and Indication
Indication

POLIVY in combination with a rituximab product, cyclophosphamide, doxorubicin, and prednisone (R-CHP) is indicated for the treatment of adult patients who have previously untreated diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) or high-grade B-cell lymphoma (HGBL) and who have an International Prognostic Index score of 2 or greater.

POLIVY in combination with bendamustine and a rituximab product (BR) is indicated for the treatment of adult patients with relapsed or refractory DLBCL, NOS, after at least two prior therapies.

Important Safety Information

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 POLARIX, of 435 patients treated with POLIVY plus R-CHP, 53% reported new or worsening peripheral neuropathy, with a median time to onset of 2.3 months. Peripheral neuropathy was Grade 1 in 39% of patients, Grade 2 in 12%, and Grade 3 in 1.6%. Peripheral neuropathy resulted in dose reduction in 4% of treated patients and treatment discontinuation in 0.7%. Among patients with peripheral neuropathy after POLIVY, 58% reported resolution after a median of 4 months.

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. Peripheral neuropathy was Grade 1 in 26% of patients, Grade 2 in 12%, and Grade 3 in 2.3%. Peripheral neuropathy resulted in POLIVY dose reduction in 2.9% 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 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, 13% of patients (58/435) in POLARIX reported infusion-related reactions after the administration of POLIVY plus R-CHP. The reactions were Grade 1 in 4.4% of patients, Grade 2 in 8%, and Grade 3 in 1.1%.

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 4.6% of patients, Grade 2 in 1.7%, and Grade 3 in 0.6%.

Symptoms occurring in ≥1% of patients included chills, dyspnea, pyrexia, pruritus, rash, and chest discomfort. Administer an antihistamine and 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 POLARIX, 90% of patients treated with POLIVY plus R-CHP had primary prophylaxis with granulocyte colony-stimulating factor (G-CSF). Grade 3–4 hematologic adverse reactions included lymphopenia (44%), neutropenia (39%), febrile neutropenia (15%), anemia (14%), and thrombocytopenia (8%).

In Study GO29365, in patients treated with POLIVY plus BR (n = 45), 42% received primary prophylaxis with G-CSF. 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. Administer prophylactic G-CSF for neutropenia in patients receiving POLIVY plus R-CHP. Consider prophylactic G-CSF administration in patients receiving POLIVY plus bendamustine and a rituximab product.

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.

In POLARIX, Grade 3–4 infections occurred in 14% (61/435) of patients treated with POLIVY plus R-CHP, and infection-related deaths were reported in 1.1% of patients.

In Study GO29365, Grade 3 or higher infections occurred in 32% (55/173) of patients treated with POLIVY, and 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. Administer prophylactic G-CSF for neutropenia as recommended.

Progressive Multifocal Leukoencephalopathy (PML)

PML has been reported after treatment with POLIVY plus bendamustine and obinutuzumab in Study GO29365 (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 proliferative tumor 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 plus R-CHP, Grade 3–4 elevation of ALT and AST developed in 1.4% and 0.7% of patients, respectively.

In Study GO29365, Grade 3 and Grade 4 transaminase elevations each developed in 1.9% 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. The small molecule component of POLIVY, monomethyl auristatin E, administered to rats 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 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 5 months after the last dose.

The Most Common Adverse Reactions

The most common adverse reactions (≥20%), excluding laboratory abnormalities, in patients with previously untreated DLBCL treated with POLIVY in combination with R-CHP are peripheral neuropathy, nausea, fatigue, diarrhea, constipation, alopecia, and mucositis. The most common Grade 3 to 4 laboratory abnormalities (≥10%) are lymphopenia, neutropenia, hyperuricemia, and anemia.

The most common adverse reactions (≥20%) in patients with relapsed or refractory DLBCL treated with POLIVY in combination with BR are neutropenia, thrombocytopenia, anemia, peripheral neuropathy, fatigue, diarrhea, pyrexia, decreased appetite, and pneumonia.

Lactation

Advise women not to breastfeed during treatment with POLIVY and for 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.; April 2023.

      POLIVY Prescribing Information. South San Francisco, CA: Genentech, Inc.; April 2023.

    • Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-Cell Lymphomas V.4.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed June 8, 2023. 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.4.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed June 8, 2023. 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.

    • 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.

    • Morrison VA, Shou Y, Bell JA, et al. Evaluation of treatment patterns and survival among patients with diffuse large B-cell lymphoma in the USA. Future Oncol. 2019;15(9):1021 -1034.

      Morrison VA, Shou Y, Bell JA, et al. Evaluation of treatment patterns and survival among patients with diffuse large B-cell lymphoma in the USA. Future Oncol. 2019;15(9):1021 -1034.

    • 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 June 20, 2023.

      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 June 20, 2023.

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