All content on this site is intended for healthcare professionals only. By acknowledging this message and accessing the information on this website you are confirming that you are a Healthcare Professional. If you are a patient or carer, please visit the Lymphoma Coalition.

The Lymphoma Hub uses cookies on this website. They help us give you the best online experience. By continuing to use our website without changing your cookie settings, you agree to our use of cookies in accordance with our updated Cookie Policy

An expert panel hosted by

The Lymphoma Hub logo and the Multiple Myeloma Hub logo

Sequencing immune-based therapies in B-cell malignancies

with Ulric Jäger, Sagar Lonial, and Krina Patel

Saturday, June 15 | 18:00-19:30 CEST

Register now

This independent education activity is sponsored by Bristol Myers Squibb. All content is developed independently by the faculty. Funders are allowed no direct influence on the content of this activity.


The Lymphoma Hub website uses a third-party service provided by Google that dynamically translates web content. Translations are machine generated, so may not be an exact or complete translation, and the Lymphoma Hub cannot guarantee the accuracy of translated content. The Lymphoma Hub and its employees will not be liable for any direct, indirect, or consequential damages (even if foreseeable) resulting from use of the Google Translate feature. For further support with Google Translate, visit Google Translate Help.

Steering CommitteeAbout UsNewsletterContact
You're logged in! Click here any time to manage your account or log out.
You're logged in! Click here any time to manage your account or log out.

Polatuzumab vedotin for naive DLBCL: Results from a phase 1b-2 trial

Jun 10, 2019

Bookmark this article

On 14 May 2019, Professor Hervé Tilly from the University of Rouen, Rouen, FR, and colleagues, published in The Lancet Oncology1 results from a phase Ib-II trial investigating the efficacy and safety of polatuzumab vedotin in combination with immnunochemotherapy in patients with naïve diffuse large B-cell lymphoma (DLBCL).

The current standard of care for DLBCL involves treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).2 However, in high-risk DLBCL patients, R-CHOP does not always lead to successful outcomes and the prognosis of patients not responding to R-CHOP is poor.2 The investigators of this trial assessed the tolerability and preliminary activity of polatuzumab vedotin together with cyclophosphamide, doxorubicin, prednisone (CHP) chemotherapy, as well as rituximab or obinutuzumab (anti-CD20 therapy), as first-line treatment for naïve DLBCL.

The primary objective of this ongoing, multicenter, open-label, non-randomized, phase Ib-II trial (NCT01992653) was treatment safety and tolerability, as well as the determination of the maximum tolerated dose of polatuzumab vedotin. Secondary endpoints included, overall response rate (ORR), complete response (CR), progression-free survival (PFS), event-free survival (EFS), and overall survival (OS).

Study design & baseline characteristics

  • N = 82 evaluable patients with histologically-confirmed B-cell non-Hodgkin lymphoma (NHL), aged ≥ 18 years:
    • For the phase Ib dose escalation phase: n = 25 (patients who had previous lymphoma treatments were also allowed)
    • For the phase II expansion phase: n = 57 (only previously untreated B-cell NHL patients with an International Prognostic Index [IPI] 2–5)
      • Patient histology (phase II): 100% diffuse large B-cell lymphoma (DLBCL)
    • Dosing:
      • Polatuzumab vedotin (pola; 21-day cycles; up to 6–8 cycles):
        • Administration schedule: on Day 2 of cycle 1 and 2 and then on Day 1 of each cycle
        • Starting dose: 1.0 mg/kg
        • Planned dose escalations: < 50% of the previous dose
        • Maximum explored dose: 1.8 mg/kg
        • Method of administration: IV infusion via syringe pump over 90 minutes for the starting dose and then over 30 minutes for following doses if well-tolerated (infusions could be slowed or interrupted accordingly)
        • Premedication: oral acetaminophen or paracetamol, and prednisone or prednisolone
      • CHP chemotherapy:
        • Cyclophosphamide: 750 mg/m2 intravenously (IV) on Day 1 of each cycle
        • Doxorubicin: 50 mg/m2 IV on Day 1 of each cycle
        • Prednisone: 100 mg orally on Days 1–5 once daily
      • Anti CD20 therapy (one of the following):
        • Rituximab (R): 375 mg/m2 IV on Day 1 of each cycle
        • Obinituzumab (G): 1000 mg IV on Days 1, 8, and 15 of cycle 1 and on Day 1 for the next cycles
      • For the phase II part, patients with naïve DLBCL were assigned to either:
        • Pola (1.8 mg/kg) + R-CHP: n = 45
        • Pola (1.8 mg/kg) + G-CHP: n = 21

Key findings

  • Recommended phase II dose of pola from phase Ib data: 1.8 mg/kg
  • Dose escalation led to only two dose-limiting events:
    • Grade 4 pulmonary embolism (1.8 mg/kg pola + R-CHP)
    • Grade 3 febrile neutropenia & Grade 3 thrombocytopenia (1.4 mg/kg pola + G-CHP)
Phase II results (DLBCL population; 1.8 mg/kg pola + R-CHP or G-CHP; n = 66)


Naïve DLBCL phase II cohort (n = 66)

95% CI


89% (n = 59)



77% (n = 55


12-month PFS



24-month PFS



12-month OS



12-month EFS



Proportion of ongoing responses at 12 months



  • No difference in PFS was observed with different number of treatment cycles (6 versus 8), anti-CD20 therapy (R versus G), or IPI categories (0–2 versus 3 or 4–5; post-hoc analysis)
  • PFS was similar in patients with different molecular DLBCL subtypes (cell or origin) and in double expressor patients (MYC and BCL2)


  • In the naïve DLBCL population who received the recommended phase II pola dose (1.8 mg/kg) the most common Grade 1–2 adverse events (AEs) observed, were the following:
    • Diarrhea: 48%
    • Nausea: 45%
    • Fatigue: 47%
    • Peripheral neuropathy: 38%
    • Constipation: 26%
    • Anemia: 26%
    • Pyrexia: 21%
  • In the same population the most common Grade ≥ 3 AEs observed were:
    • Neutropenia: 30%
    • Febrile neutropenia: 18%
    • Thrombocytopenia: 9%
  • The most common serious AEs were:
    • Febrile neutropenia: 14%
    • Neutropenia: 6%
    • Pneumonia: 6%
  • In the same population, 11% of patients discontinued treatment due to AEs after receiving 1–5 cycles and 8% of patients had a pola dose reduction
  • A higher incidence of neutropenia and thrombocytopenia was observed in patients receiving G-CHP than R-CHP
  • Median time to resolution for all grades peripheral neuropathy (range): 2.4 (0.8–6.5) months
  • Median time to resolution for Grade 2–3 peripheral neuropathy (range): 4.9 (1.0–9.1) months
  • Four DLBCL patients (6%) died during the study either due to Grade 5 AEs (n = 2; atrial fibrillation, septic shock) or due to disease progression (n = 2)


The results of this phase Ib-II trial indicate that pola in combination with G-CHP or R-CHP has a manageable toxicity profile and leads to promising response outcomes in previously untreated patients with DLBCL

  1. Tilly H. et al. Polatuzumab vedotin in combination with immunochemotherapy in patients with previously untreated diffuse large B-cell lymphoma: an open-label, non-randomised, phase 1b-2 study. Lancet Oncol. 2019 May 14. pii: S1470-2045(19)30091-9. DOI: 10.1016/S1470-2045(19)30091-9 [Epub ahead of print]
  2. Sehn, L.H. et al. 2015. Diffuse large B-cell lymphoma: optimizing outcome in the context of clinical and biologic heterogeneity. Blood 125, 22–32.

Understanding your specialty helps us to deliver the most relevant and engaging content.

Please spare a moment to share yours.

Please select or type your specialty

  Thank you


Subscribe to get the best content related to lymphoma & CLL delivered to your inbox