Polatuzumab Vedotin

Polatuzumab vedotin is an antibody-drug conjugate being studied in clinical trials for the treatment of various types of lymphoma, including diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma. This article summarizes key information from several clinical trials investigating polatuzumab vedotin alone or in combination with other drugs. The trials aim to evaluate the safety, efficacy, and optimal dosing of polatuzumab vedotin in patients with relapsed or refractory lymphomas.

Table of Contents

What is Polatuzumab Vedotin?

Polatuzumab vedotin is a medication used to treat certain types of blood cancers. It is known by the brand name Polivy[3]. Polatuzumab vedotin is a type of drug called an antibody-drug conjugate (ADC). This means it combines a targeted antibody with a chemotherapy drug[2].

The medication has a few other scientific names you may hear, including:

  • DCDS4501A
  • RO7596
  • FCU 2711

How Polatuzumab Vedotin Works

Polatuzumab vedotin works in a unique way to target and kill cancer cells. The antibody part of the drug attaches to a protein called CD79b, which is found on the surface of certain types of cancer cells. Once attached, the drug releases a potent chemotherapy agent called MMAE (monomethyl auristatin E) into the cancer cell[1].

MMAE works by stopping cancer cells from dividing and growing. It does this by interfering with structures inside the cell called microtubules, which are important for cell division. This mechanism is similar to how another chemotherapy drug called vincristine works[1].

Conditions Treated with Polatuzumab Vedotin

Polatuzumab vedotin is used to treat several types of blood cancers, including:

  • Diffuse Large B-Cell Lymphoma (DLBCL): This is the most common type of non-Hodgkin lymphoma, a cancer that starts in white blood cells called lymphocytes[1][2].
  • Follicular Lymphoma: Another type of non-Hodgkin lymphoma that typically grows slowly[5].
  • High-Grade B-Cell Lymphoma: A fast-growing type of lymphoma[2].
  • Burkitt Lymphoma: A rare but aggressive form of non-Hodgkin lymphoma[6].
  • Mantle Cell Lymphoma: A rare type of B-cell non-Hodgkin lymphoma[6].
  • Marginal Zone Lymphoma: A slow-growing type of B-cell non-Hodgkin lymphoma[6].
  • Transformed Non-Hodgkin Lymphoma: When a slow-growing lymphoma changes into a more aggressive form[6].
  • Richter Syndrome: A rare condition where chronic lymphocytic leukemia or small lymphocytic lymphoma transforms into an aggressive lymphoma[6].
  • Hodgkin Lymphoma: A type of lymphoma that involves Reed-Sternberg cells[6].

Polatuzumab vedotin is often used when other treatments have not worked or when the cancer has come back after previous treatment[4].

How Polatuzumab Vedotin is Given

Polatuzumab vedotin is given as an intravenous (IV) infusion, which means it’s delivered directly into your bloodstream through a vein. The typical dose is 1.8 milligrams per kilogram of body weight[8].

Treatment is usually given in cycles. Each cycle is typically 21 days for patients with diffuse large B-cell lymphoma and 28 days for patients with follicular lymphoma. The number of cycles can vary, but often patients receive up to 6 cycles of treatment[8].

Polatuzumab vedotin is often given in combination with other cancer medications. Common combinations include:

  • Polatuzumab vedotin + bendamustine + rituximab (known as Pola-BR)[1]
  • Polatuzumab vedotin + rituximab + cyclophosphamide + doxorubicin + prednisone (known as Pola-R-CHP)[2]
  • Polatuzumab vedotin + obinutuzumab[8]

Clinical Trials and Research

Polatuzumab vedotin has been and continues to be studied in various clinical trials. These studies help researchers understand how well the drug works, its safety, and how it compares to other treatments. Some key areas of research include:

  • Using polatuzumab vedotin before stem cell transplants in patients with relapsed or refractory lymphoma[1].
  • Combining polatuzumab vedotin with other medications for previously untreated lymphomas[2].
  • Using polatuzumab vedotin after stem cell transplants[3].
  • Studying the effectiveness of polatuzumab vedotin in real-world clinical practice[4].
  • Investigating polatuzumab vedotin in combination with new drugs like mosunetuzumab for untreated follicular lymphoma[5].
  • Exploring the use of polatuzumab vedotin in post-transplant lymphoproliferative disorder (PTLD)[6].
  • Testing polatuzumab vedotin as part of a treatment strategy before and after CAR-T cell therapy[7].

Potential Side Effects

Like all medications, polatuzumab vedotin can cause side effects. Common side effects may include:

  • Fatigue
  • Nausea
  • Fever
  • Decreased appetite
  • Diarrhea

More serious side effects can include:

  • Peripheral neuropathy: This is nerve damage that can cause numbness, tingling, or pain, usually in the hands and feet[8].
  • Infections: The medication can lower your white blood cell count, making you more susceptible to infections.
  • Infusion reactions: These can occur during or shortly after receiving the medication through IV.
  • Tumor lysis syndrome: This is a condition that can occur when cancer cells break down quickly, releasing their contents into the blood.

Your healthcare team will monitor you closely for these and other potential side effects throughout your treatment[8].

Aspect Details
Drug Name Polatuzumab vedotin
Drug Type Antibody-drug conjugate
Target CD79b on B cells
Conditions Studied Diffuse large B-cell lymphoma, Follicular lymphoma, Other non-Hodgkin lymphomas, Hodgkin lymphoma
Administration Intravenous infusion
Common Dosing 1.8 mg/kg every 21 days
Combination Therapies Rituximab, Obinutuzumab, Bendamustine, Cyclophosphamide, Doxorubicin, Prednisone, Glofitamab
Key Outcomes Measured Overall response rate, Complete response rate, Progression-free survival, Duration of response, Overall survival, Safety/side effects, Pharmacokinetics
Trial Phases Phase I, Phase II
Patient Populations Relapsed/refractory lymphomas, Newly diagnosed lymphomas, Pre- and post-stem cell transplant

Ongoing Clinical Trials on Polatuzumab Vedotin

  • Study Comparing Zilovertamab Vedotin with Drug Combination for Untreated Patients with Diffuse Large B-Cell Lymphoma

    Recruiting

    1 1 1
    Investigated diseases:
    Belgium Germany Ireland Italy Poland
  • Study on the Safety and Tolerability of Epcoritamab with Drug Combination for Patients with B-cell Non-Hodgkin Lymphoma

    Recruiting

    1 1 1
    Czechia Denmark France Germany Hungary The Netherlands +1
  • Study on MB-CART2019.1 for Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma Not Eligible for High-Dose Chemotherapy and Stem Cell Transplantation

    Recruiting

    1 1 1
    Austria Belgium Croatia Czechia Finland France +9
  • Study on the Effectiveness and Safety of Cytarabine, Tafasitamab, and Lenalidomide for Patients with Relapsed Diffuse Large B-Cell Lymphoma

    Not yet recruiting

    1 1 1
    Poland
  • Study Comparing R-MINI-CHOP and R-MINI-CHP with Polatuzumab Vedotin for Treating Diffuse Large B-Cell Lymphoma in Patients Aged 80 and Older or Frail Patients Aged 75 and Older

    Not yet recruiting

    1 1 1 1
    Denmark Estonia Finland Italy Norway Sweden
  • Study on the Effectiveness of Polatuzumab, Bendamustine, and Rituximab for Patients with Relapsed or Refractory Mantle Cell Lymphoma

    Not recruiting

    1 1 1
    Investigated diseases:
    Austria
  • Study on the Effectiveness and Safety of Polatuzumab Vedotin, Rituximab, and CHP in Patients with Untreated Diffuse Large B-Cell Lymphoma

    Not recruiting

    1 1 1
    Austria Belgium Czechia France Germany Italy +2
  • Study of Rituximab, Polatuzumab Vedotin, and Glofitamab for Untreated Aggressive B-cell Lymphoma in Patients Over 60 Not Eligible for Full R-CHOP

    Not recruiting

    1 1 1
    Investigated diseases:
    Austria Germany
  • Study Comparing Polatuzumab Vedotin with Rituximab, Ifosfamide, Carboplatin, and Etoposide for Adults with Relapsed or Refractory Diffuse Large B-Cell Lymphoma

    Not recruiting

    1 1 1 1
    Austria Germany Spain
  • Study of Mosunetuzumab and Polatuzumab Vedotin for Patients with Diffuse Large B-Cell Lymphoma After Initial Treatment or in Elderly/Unfit Untreated Patients

    Not recruiting

    1 1 1
    Poland Spain

Glossary

  • Antibody-drug conjugate: A type of targeted cancer therapy that combines an antibody with a potent anti-cancer drug. The antibody helps deliver the drug specifically to cancer cells.
  • Complete response (CR): The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured.
  • Diffuse large B-cell lymphoma (DLBCL): An aggressive (fast-growing) type of non-Hodgkin lymphoma that starts in B cells.
  • Follicular lymphoma: A usually slow-growing type of non-Hodgkin lymphoma that starts in B cells.
  • Hodgkin lymphoma: A type of cancer that starts in white blood cells called lymphocytes.
  • Intravenous (IV): Given through a vein.
  • Non-Hodgkin lymphoma: A group of blood cancers that start in lymphocytes. There are many different types.
  • Overall response rate (ORR): The percentage of patients whose cancer shrinks or disappears after treatment.
  • Partial response (PR): A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment.
  • Pharmacokinetics: The study of how a drug is absorbed, distributed, metabolized, and eliminated by the body.
  • Progression-free survival (PFS): The length of time during and after treatment that a patient lives with the disease but it does not get worse.
  • Relapsed: The return of a disease or the signs and symptoms of a disease after a period of improvement.
  • Refractory: Not responding to treatment.

References

  1. https://clinicaltrials.gov/study/NCT04535102
  2. https://clinicaltrials.gov/study/NCT04479267
  3. https://clinicaltrials.gov/study/NCT04491370
  4. https://clinicaltrials.gov/study/NCT04624893
  5. https://clinicaltrials.gov/study/NCT05410418
  6. https://clinicaltrials.gov/study/NCT06040320
  7. https://clinicaltrials.gov/study/NCT06071871
  8. https://clinicaltrials.gov/study/NCT02257567