Background: Transplant-ineligible patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) have a poor prognosis (Gisselbrecht C, et al. Br J Haematol 2018). Several treatment options are available, including platinum-based chemotherapies such as oxaliplatin plus rituximab and gemcitabine (R-GemOx). Adding polatuzumab vedotin to R-GemOx (Pola-R-GemOx) may improve outcomes for patients with a continued unmet medical need. Pola-R-GemOx is an investigational combination. The safety of polatuzumab vedotin and platinum-based therapy combinations must be considered as both are associated with neuropathy. POLARGO (NCT04182204; MO40598) is a Phase III, multicenter, open-label, randomized trial evaluating the safety and efficacy of Pola-R-GemOx vs R-GemOx in patients with R/R DLBCL.
Aims: To present the results from the safety run-in stage of POLARGO.
Methods: The primary endpoint is the safety and tolerability of polatuzumab vedotin (1.8 mg/kg) + R-GemOx (R, 375 mg/m2; Gem, 1000 mg/m2; Ox, 100 mg/m2) given every 21 days for up to 8 cycles. Safety was assessed by the incidence, nature, and severity of adverse events (AEs; NCI CTCAE v5.0), with a focus on peripheral neuropathy (PN). Dose interruptions and reductions were used to assess tolerability. Granulocyte-colony stimulating factor was given as primary prophylaxis with each cycle (C) of therapy; anti-infective prophylaxis for pneumocystis and herpes virus was mandatory. All patients provided informed consent.
Results: As of October 26, 2021, 15 patients were enrolled, and 11 (73%) received ≥4 cycles of Pola-R-GemOx. Median age was 76 (range 47–87) years, 10 (67%) patients had an IPI score of 3–5, 7 (47%) had ≥2 prior therapy lines, and 8 (53%) were refractory to last treatment. Grade 3–4 AEs were reported in 5 (33%) patients: thrombocytopenia (20%) and neutropenia (13%) were the most common. Two (13%) patients had serious AEs (grade 3 febrile neutropenia and grade 3 infection [n=1 each]). There were no grade 5 AEs or AEs leading to drug discontinuation. Eight (53%) patients had grade 1 or 2 PN; there were no cases of grade ≥3 PN. Three (20%) patients had drug interruptions due to PN. Two (13%) patients had a dose reduction of polatuzumab vedotin and oxaliplatin due to PN at C5 and C8, respectively; one patient (7%) had a dose reduction of polatuzumab vedotin due to grade 4 thrombocytopenia at C2.
End-of-treatment (EOT) objective response rate was 40% (95% confidence interval [CI]: 16–68) and complete response rate was 27% (95% CI: 8–55); 7 (47%) patients had progressive disease at EOT. Ten (67%) patients received subsequent therapies following Pola-R-GemOx, including CAR T-cell therapy (n=3) and stem-cell transplant (n=1).
Summary/Conclusion: In the safety run-in stage, Pola-R-GemOx was safe and tolerable. PN was manageable with dose interruptions and reductions; no cases of grade ≥3 PN were observed. The toxicity of this combination did not compromise delivery of subsequent treatments. POLARGO is currently enrolling patients to receive Pola-R-GemOx vs R-GemOx; results will be presented at a future meeting.