Polatuzumab vedotin in combination with venetoclax and rituximab for patients with R/R DLBCL

Patients with released/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are ineligible for transplant have limited treatment options and a poor prognosis; however, novel combination therapies may improve outcomes.¹ Polatuzumab vedotin, an antibody-drug conjugate targeting CD79b, is being evaluated in combination with several other agents for the treatment of patients with R/R DLBCL.¹ The Lymphoma Hub previously covered outcomes of polatuzumab vedotin in combination with venetoclax and rituximab and primary analysis results from the phase Ib/II GO29834 trial (NCT02600897) investigating the combination of polatuzumab vedotin, rituximab, and lenalidomide in patients with R/R DLBCL. Here, we summarize the results from the GO29834 trial, published by Abrisqueta et al.¹ in Lancet Haematology.

Study design¹

• This was an open-label, multicenter, phase Ib/II trial (Figure 1)
• The primary safety and efficacy outcomes were the maximum tolerated dose of lenalidomide and the complete response rate, respectively

IV, intravenous; RP2D, recommended phase II dose.
*Data from Abrisqueta, et al.¹

Key findings¹

• In total, 57 patients were included (phase Ib, n = 18; phase II, n = 39) with a median age of 71 years.
• The efficacy cohort (n = 49) included patients from cohort C (n = 10) of the phase Ib portion and patients from the phase II portion (n = 39), while the safety cohort included all patients (n = 57); median follow-up was 11.8 months.

Phase Ib

• No dose-limiting toxicities were observed
  • One patient in cohort C had a fatal adverse event (AE) deemed unrelated to the study treatment
• 20 mg lenalidomide was chosen as the recommended phase II dose

Safety

• Overall, 98%, 77%, and 40% of patients experienced ≥1 any grade, Grade 3–4, and serious AEs, respectively.
  • The most common Grade 3–4 AEs were neutropenia (61%), and thrombocytopenia (14%).
  • The most common serious AEs were infection (18%), pyrexia (18%), and tumor flare (4%).
• Overall, 35 patients died, most commonly due to disease progression (n = 26) and AEs (n = 5).
  • One patient died due to a treatment-related AE (neutropenic sepsis).

Induction response

• Induction response rates are shown in Figure 2
• Median duration of response was 9.3 months

*Data from Abrisqueta, et al.¹

Survival outcomes

• Median progression-free survival (PFS) and overall survival were 6.0 months and 11.9 months, respectively.
  • Among patients with a complete response, median PFS and overall survival were not reached.
• Estimated 12- and 24-month PFS rates are shown in Figure 3.

PFS, progression-free survival.
*Data from Abrisqueta, et al.¹

 

Key learnings
Polatuzumab vedotin in combination with rituximab and lenalidomide was associated with clinical activity and an acceptable safety profile in patients with R/R DLBCL. While responses were encouraging, they did not meet the prespecified threshold of 40%.