Polatuzumab Vedotin Is Safe, Efficacious, But Yields Short Duration of Response in R/R LBCL

Although treatment with polatuzumab vedotin (Polivy) after anti-CD19 CAR T-cell therapy was safe and effective for patients with relapsed/refractory large B-cell lymphoma, it had a short duration of response.

Polatuzumab vedotin-piiq (Polivy) demonstrated promising safety and efficacy in patients with relapsed/refractory large B-cell lymphoma (LBCL) who have previously received anti-CD19 CAR T-cell therapy; however, investigators noted that the agent yielded a short duration of response.1

A total of 25 patients achieved a response, including 8 a complete responses and 17 partial responses. The median duration of response was 11 weeks (95% CI, 5-17). Moreover, after a median follow-up of 47 weeks, 81% of patients had progressed or died. The median progression-free survival (PFS) was 10 weeks (95% CI, 5-15), and the median overall survival (OS) was 17 weeks (95% CI, 14-21).

“Studies aimed at better characterizing intrinsic mechanism of resistance, including upregulation of BCL2 family proteins, to favor the development of more effective [polatuzumab vedotin]–based combination strategies for these patients, are warranted,” the investigators wrote.

A total of 57 patients were enrolled in the study. Patients received polatuzumab at a dose of 1.8 mg/kg intravenously every 3 weeks, with dose reductions administered based on toxicity. It was also variably combined with bendamustine (Bendeka) and rituximab (Rituxan), which has previously been approved by the FDA.2

Patients were a median age of 60 years, and 49% of patients were older than 60 years. Seventy percent of patients were male. Two of 53 patients had a ECOG performance status of 3 or 4, and 77% had diffuse LBCL or high-grade B-cell lymphoma. The main disease sites included bone marrow biopsy involvement (13%) and prior central nervous system (CNS) lymphoma (5%). Almost half of all patients had over 2 or more lines of therapy before CAR T-cell therapy (44%). Other previous therapies included autologous stem cell transplant (30%), previous allogeneic stem cell transplant (4%), and primary refractory to CAR T (32%).

Patients had a median absolute neutrophil count of 2.9 109/L, hemoglobin of 10.2 g/dL, and platelet count of 102 109/L. Lactate dehydrogenase (LDH) was above the normal limit in 84% of patients and the median bilirubin total was 0.5 mg/dL. Additionally, most patients were CD19-positive (84%) and all were CD79-positive (100%).

In total, 98% of patients received the full polatuzumab dose and underwent a median of 2 cycles of treatment. Additionally, 61% of patients received concomitant bendamustine and 95% received concomitant rituximab.

Progressive disease was observed in 50% of patients, 4% had stable disease, and 2% had disease that was not evaluable. No factors were found to be associated with overall response rate.

Overall, 91% of patients discontinued treatment. Reasons for discontinuation included disease progression (70%), complete response or patient decision (13%), receiving an allogeneic stem cell transplant (6%), clinical trial (2%), and adverse effects, specifically peripheral neuropathy (2%).

Findings from the multivariate analysis indicated that a maintained association was identified for patients with bone marrow involvement (HR, 5.2; 95% CI, 1.8-15.0; P = .003) and elevated lactate dehydrogenase (HR, 5.0;1.4-16.0; P = 01).

These findings were presented at the 2022 Tandem Meeting.

References

  1. Strati P, Rosenthal AC, Gouni S, et al. An updated multi-center retrospective study of polatuzumab for patients with large B-cell lymphoma relapsed after standard of care CAR T-cell therapy. Presented at the 2022 Tandem Meeting; Salt Lake City, UT; April 23-26, 2022.
  2. FDA approves polatuzumab vedotin-piiq for diffuse large B-cell lymphoma. News Release. FDA June 10, 2019. Accessed May 3, 2022. https://bit.ly/3KIpvA9