Glofitamab in combination with polatuzumab vedotin demonstrates high and durable efficacy in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) in the second-line (2L) and third-line and later (3L+) settings: A subgroup analysis Free

Background: Despite recent advances, R/R LBCL remains clinically challenging with poor outcomes and a critical need for effective and durable treatment options, particularly for patients with high-risk characteristics. In this open-label, multicenter, Phase Ib/II study (NCT03533283), glofitamab in combination with polatuzumab vedotin (Glofit+Pola) demonstrated high and durable efficacy and manageable safety in patients with R/R LBCL after ≥1 line of therapy, including in those with high-grade B-cell lymphoma (HGBCL; Hutchings, et al. ASH 2024). We report the efficacy of Glofit+Pola in patients with R/R LBCL, with subgroup analyses in the 2L and 3L+ setting.

Methods: Patients aged ≥18 years with R/R LBCL after ≥1 prior systemic therapy were included. After obinutuzumab pre-treatment on Cycle (C)1 Day (D)1, glofitamab was administered as step-up dosing in C1 (D8, 2.5mg; D15, 10mg) then the target dose of 30mg on D1 of C2–12 (21-day cycles), and polatuzumab vedotin (1.8mg/kg) was given on C1D2 and D1 of C2–6 (21-day cycles). Patients received fixed treatment of 12 cycles of glofitamab and six cycles of polatuzumab vedotin unless treatment was discontinued. Efficacy was assessed by overall response, durability of response, and survival outcomes.

Results: At the clinical cut-off date (September 2, 2024), 129 patients with LBCL were enrolled (HGBCL, n=44) and treated with Glofit+Pola: 53 (41.1%) patients in the 2L and 76 (58.9%) in the 3L+ subgroups. In the 2L and 3L+ subgroups, 66.0% (n=35) and 59.2% (n=45) of patients, respectively, were refractory to their first-line therapy; 88.2% (n=67) of patients in the 3L+ subgroup were refractory to any prior therapy. Prior chimeric antigen receptor T-cell therapy was reported in 1.9% (n=1; refractory) of patients in the 2L subgroup and 35.5% (n=27; 21 refractory) of patients in the 3L+ subgroup. The median survival follow up was 32.7 months (range: 0–55; 2L: 29.7 months [range: 1–55]; 3L+: 33.6 months [range: 0–55]).

The overall response rate (ORR) and complete response (CR) rate in the overall population were 80.6% and 62.0%, respectively. Comparable response rates were seen in patients in the 2L (ORR: 79.2%; CR: 66.0%) and 3L+ (ORR: 81.6%; CR: 59.2%) subgroups.

The median (m) duration of response (DOR) and duration of CR (DOCR) in the overall population were 24.3 months (95% confidence interval [CI]: 15.0–37.8) and 31.8 (95% CI: 21.9–not estimable [NE]), respectively. Similarly, in the 2L subgroup, the mDOR was 31.8 months (95% CI: 8.8–NE) and the mDOCR was also 31.8 months (95% CI: 17.8–NE). In the 3L+ subgroup, the mDOR and mDOCR were 23.5 months (95% CI: 10.9–37.8) and 37.8 months (95% CI: 21.9–NE), respectively.

In the overall population, the 12- and 24-month DOR rates were 62.4% (95% CI: 52.5–72.2) and 50.5% (95% CI: 39.6–61.4), respectively. The 12- and 24-month DOR rates, respectively, were 64.6% (95% CI: 49.5–79.6) and 53.3% (95% CI: 36.3–70.3) for the 2L subgroup, and 60.7% (95% CI: 47.7–73.7) and 48.6% (95% CI: 34.5–62.7) for the 3L+ subgroup.

The 12- and 24-month DOCR rates were also comparable across the overall population and 2L and 3L+ subgroups. In the overall population, 12- and 24-month DOCR rates were 75.1% (95% CI: 65.1–85.2) and 59.9% (95% CI: 47.5–72.3), respectively. Similarly, the 2L and 3L+ subgroups, respectively, achieved 12-month DOCR rates of 72.8% (95% CI: 57.5–88.0) and 76.7% (95% CI: 63.2–90.2), and 24-month DOCR rates of 59.3% (95% CI: 40.7–77.9) and 60.4% (95% CI: 43.8–77.0).

Median progression-free survival (PFS) in the overall population was 12.3 months (95% CI: 8.8–27.7). In the 2L subgroup, the mPFS was 17.7 months (95% CI: 8.1–NE) and in the 3L+ subgroup mPFS was 12.3 months (95% CI: 5.6–25.7).

Safety profiles in the 2L and 3L+ subgroups were comparable and manageable, and no new safety signals were observed.

Updated data, with >3 years of follow up, along with response in molecular subgroups, including cell of origin, will be presented.

Conclusions: Glofit+Pola in heavily pre-treated patients with R/R LBCL, including HGBCL, demonstrated high and durable efficacy, with comparable response rates and durability observed in the overall population and across both the 2L and 3L+ subgroups. These findings support the potential of this drug combination as an effective treatment option in a population with limited therapeutic alternatives.