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

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

• 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