Polatuzumab vedotin (Pola) is an antibody-drug conjugate targeting CD79b, delivering monomethyl auristatin E, and has been applied in B-cell lymphoma treatment. The R-pola-CHP in Polarix(G. Salles et al, the NEJM, 2022) study and pola-BR in the phase Ib/II trial(Laurie H. Sehn et al, J Clin Oncol, 2019) showed significantly higher CR rate and ORR in Diffuse Large B-cell Lymphoma(DLBCL). However, results of real world was not clear. Real-world study in Turkey has summarized 71 R/R DLBCL treated with pola-BR, drawing 48% ORR and 32% CR rate(Mehmet Sinan Dal et al, Annals of Hematology, 2023). To clarify if pola based regimen could show safety and efficacy in DLBCL in real-word settings, as proved in China in March 2023, a real-world study was conducted. This study compiles efficacy and safety of pola-related regimens as first-line treatment and salvage treatment for DLBCL.

This multicenter retrospective study included patients diagnosed as untreated DLBCL or R/R DLBCL treated with Pola at three academic hospitals in Beijing between May 2023 and May 2024. The evaluation and adverse effects(AE) were strictly observed during a median follow-up of 8 months. All patients received up to 8 cycles of treatment based on the investigator's judgment. The different regimens and tumor characteristics were recorded. The treatment response to Pola in interim evaluation and junction evaluation was determined using imaging modalities such as positron emission tomography (PET).

Totally 55 patients were enrolled, including 41 patients with untreated DLBCL and 14 patients with R/R DLBCL. In untreated DLBCL, the median age was 69 years(range:32-86) and male patients accounted for 37%. Eleven patients whose median age was 80 years(range:73-86) were treated with Pola-R2. Other 30 patients whose median age was 67 years(range:32-79) were treated with pola plus chemotherapy. Among those, 29 patients received Pola-R-CHP-like therapy, including R-Pola-CHP(n=27), R-Pola-CHP-MTX(n=2), and 1 patient received R-Pola-EPCH. The untreated DLBCL with chemotherapy group achieved a 100% overall response rate (ORR), and the untreated DLBCL without chemotherapy group had 84% ORR. Forty patients were evaluated in interim as 31 in CR(CR rate=78%), 8 in PR and 1 in PD. Twenty-six patients were evaluated in junction with 6 cycles in median of treatments as 22 in CR(CR rate=84.6%), 2 in PR and 2 in PD. The quit to treatments was due to PD evaluation(n=2), severe infection(n=1). During the follow-up of 8 months, there was no relapse patient evaluated as CR or PR before. The patients treated with pola plus chemotherapy had higher but not significantly ORR than those without chemotherapy(100% v 91%, p=0.22). Both groups showed similar severe AE rate(77% vs 82%, p=0.10): neutropenia(70% v 73%), liver injury(13% v 18%), and infection(17% v 18%). For R/R DLBCL, 11 patients were treated with pola plus chemotherapy(R-Pola-CHP n=4, Pola-BR n=4, R-Pola-DHAP n=3), and 3 patients received pola based chemo-free regimen(Pola-R2 n=2, Pola n=1). The ORR in R/R DLBCL was approximately 76%. Among 11 patients treated with pola plus chemotherapy, 2 patients were evaluated as PD and treated with palliative radiotherapy or chimeric antigen receptor T-cell immunotherapy, while others had CR or PR. Among 3 patients treated with chemo-free regimen, 2 patients were evaluated as CR and 1 patient did not receive further treatment after evaluated as PD in interim. There were 8 patients evaluated in junction as 6 in CR, 2 in PR. The median OS and PFS in both all groups were not reached. The most common grade 3 to 4 AE was neutropenia (n=37, 67.3%), including 70% untreated DLBCL and 57% R/R DLBCL. Grade 3-4 anemia occurred in 45.4% and thrombocytopenia occurred in 30.9%. There were 9 patients showing liver injury (grade 3-4 n=2) and 9 patients showing infection (grade 3-4 n=7) of lung, urinary system or gastrointestinal tract. One patient died due to pneumonia. Other AE including peripheral nausea(n=17), fatigue(n=15) and neuropathy(n=5) were all grade 1-2.

This real-world study shows that pola based therapy has a good efficacy and safety in either first-line or salvage therapy, which was comparable with previous researches. Pola-R2 is suitable for elderly patients with untreated DLBCL, offering similar CR rate and better tolerance. For R/R DLBCL, pola based chemotherapy has a high remission rate and could serve as bridging therapy to other novel therapies.

Disclosures

No relevant conflicts of interest to declare.

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2024
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