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FDA approval granted to polatuzumab vedotin in combination with bendamustine and rituximab for R/R DLBCL

Jun 13, 2019
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The United States (US) Food & Drug Administration (FDA) have granted accelerated approval to polatuzumab vedotin (Pola) in combination with bendamustine (B) and rituximab (R) (BR) for the treatment of patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are not eligible for transplant. This is the first chemoimmunotherapy to be approved in this setting.1,2

Background: Pola

Pola is an antibody-drug conjugate which binds to CD79b on B-cells, specifically delivering a cytotoxic dose of monomethyl auristatin E (MMAE), which is a microtubule inhibitor.2,3 CD79b is a viable target in DLBCL as it is ubiquitously expressed in mature B-cell lymphomas.3

Founding trial information: GO29365 (NCT02257567)

The phase Ib/II randomized trial compared Pola + BR to BR. Another arm of this trial investigated Pola + B + obinutuzumab (Pola + BG) to BG. The FDA approval is based on the results of the randomized phase Ib/II results presented at ASCO 20184 and ASH 20182 which are summarized below.

Results given as Pola + BR versus BR

Study design, phase II:2

  • N = 80
  • Randomization (1:1):
    • Pola + BR (n = 40)
    • BR (n = 40)
  • Dosing as below, every 21 days for up to 6 cycles:
    • Pola: 1.8mg/kg
    • B: 90mg/m2/day x 2 days
    • R: 375mg/m2
  • Follow-up (phase II): 22.3 months

Efficacy: phase II:1,2

Table 1: Efficacy results for Pola + BR compared to BR in phase II portion of the study as assessed by independent review committee at the end of treatment

 

Pola + BR 
(n = 40)

BR 
(n = 40)

Hazard ratio (HR)

P value

Complete response rate

40%

18%

-

0.026

Median duration of response (DoR)

10.3 months

(5.6–not reached [NR])

4.1 months

(2.6–12.7)

0.44

 

0.032

Median progression-free survival (PFS)

7.6 months

(6.0–17.0)

2.0 months

(1.5–3.7)

0.34

 

<0.0001

Median overall survival (OS)

12.4 months

(9.0–NR)

4.7 months

(3.7–8.3)

0.42

 

0.0023

  • Of patients who partially or completely responded (n = 25)
    • Duration of response (DOR) ≥6 months: 16 (64%)
    • DOR ≥12 months: 12 (48%)

Safety, phase II:4

  • Manageable toxicity
  • Most common adverse events (AEs): neutropenia, thrombocytopenia, anemia, peripheral neuropathy, fatigue, diarrhea, fever, decreased appetite and pneumonia1
  • Most common grade 3–5 AEs higher in pola + BR vs BR
    • Cytopenias
    • Febrile neutropenia
    • Infections
  1. FDA approves first chemoimmunotherapy regimen for patients with relapsed or refractory diffuse large B-cell lymphoma. https://www.fda.gov/news-events/press-announcements/fda-approves-first-chemoimmunotherapy-regimen-patients-relapsed-or-refractory-diffuse-large-b-cell [accessed 2019 Jun 12]
  2. Sehn L.H. et al. Polatuzumab Vedotin (Pola) Plus Bendamustine (B) with Rituximab (R) or Obinutuzumab (G) in Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL): Updated Results of a Phase (Ph) Ib/II Study. Blood. 2018 Nov 21. DOI: 10.1182/blood-2018-99-118551
  3. 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 Onc. 2019 May 14. DOI: 10.1016/S1470-2045(19)30091-9
  4. Sehn L.H. et al. Randomized phase 2 trial of polatuzumab vedotin (pola) with bendamustine and rituximab (BR) in relapsed/refractory (r/r) FL and DLBCL. J Clin Onc. 2018 Jun 01. DOI: 10.1200/JCO.2018.36.15_suppl.7507
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