MULTICENTER REAL-WORLD OUTCOMES OF FRONTLINE POLA-R-CHP IN TREATMENT NAÏVE DLBCL

Abstract

Introduction: Incorporation of polatuzumab vedotin into initial therapy of diffuse large B-cell lymphoma (DLBCL) became a standard of care (SOC) based on the POLARIX trial, which demonstrated improvement in progression free survival (PFS) with pola-R-CHP compared to R-CHOP. In this study we evaluate the safety and efficacy of SOC frontline pola-R-CHP for treatment naïve DLBCL.

Methods: We performed a multicenter retrospective study including patients (pts) from 17 US centers. Pts with treatment naïve DLBCL who received pola-R-CHP as frontline therapy outside of the setting of a clinical trial were eligible. The primary objective was to evaluate the PFS of SOC pola-R-CHP in frontline DLBCL. Secondary objectives included evaluating the safety of the regimen as well as secondary measures of efficacy such as overall response rate (ORR), complete response rate (CRR), overall survival (OS), and time to next treatment (TTNT).

Results: A total of 535 pts treated with pola-R-CHP between August 2021 to September 2024 were included. At least one cycle of alternate treatment was given in 28% pts before switching to pola-R-CHP (78% of these pts received R-CHOP). The median age was 67 years (range 22–90), 41% were female, 17% had ECOG ≥ 2, 89% had advanced stage, 45% had > 1 extranodal site, 63% had elevated LDH, 63% had an IPI of 3–5, 33% had bulky disease (≥ 7.5 cm), 3.3% had central nervous system involvement, 29% were double expressor, 3.9% were double/triple hit, 34% had germinal center B-cell subtype (GCB) and 59% had non-GCB subtype by Hans.

ORR was 92% with a CRR of 80% in all pts; ORR was 93% versus 92% (CRR 77% vs. 81%) for GCB versus non-GCB. At a median follow up of 11 months (range 0.5–32), 1-year PFS was 81% (95% CI: 77%–84%) among all pts, 78% for GCB versus 82% for non-GCB; 1-year OS was 91% (95% CI: 87%–93%) among all pts and 91% for both cell of origin (COO) subgroups. Subsequent treatment was given in 16% pts with median TTNT 5.8 months (range 0.8–18).

With respect to safety, 37% developed any grade neuropathy with 1.1% grade ≥ 3, 20% had grade ≥ 3 infection, 3.4% had cardiomyopathy, 31% had grade ≥ 3 neutropenia, 15% had grade ≥ 3 febrile neutropenia, and 15% had grade ≥ 3 thrombocytopenia. 31% were hospitalized and 6.0% had ICU admission for treatment-related adverse events. Treatment was discontinued in 13% due to toxicity (4.5%), progression (3.6%), or other reasons (4.7%). Seven deaths (1.3%) were deemed to be related to pola-R-CHP.

In univariate Cox models, > 1 extranodal sites, bulky disease, CNS involvement, and double/triple hit were associated with inferior PFS (p < 0.05) and ECOG ≥ 2, elevated LDH, and IPI 3–5 were associated with inferior OS and PFS (p < 0.05). COO was not significantly associated with PFS or OS.

Conclusion: The results of our study suggest that SOC pola-R-CHP is safe and effective for treatment naïve DLBCL, with outcomes similar to those found in POLARIX and no differences in outcomes based on COO.

Research funding declaration: GNE, ADC-T, Genmab/Abbvie, Ipsen

Keywords: Aggressive B-cell non-Hodgkin lymphoma

Potential sources of conflict of interest:

S. K. Thiruvengadam

Consultant or advisory role: Abbvie, Ipsen, Kite

Other remuneration: Research funding- GNE, Ipsen, ADC-T, Genmab/Abbvie

A. Bock

Consultant or advisory role: Genmab/Abbvie, Regeneron

C. Ujjani

Consultant or advisory role: abbvie, genmab, adc therapeutics, beigene, atara, astrazeneca

Other remuneration: abbvie, pharmacyclics, lilly, gilead, astrazenca

H. Cherng

Honoraria: ADC-Therapeutics

D. Russler-Germain

Consultant or advisory role: Regeneron, Tempus, Ipsen

A. F. Herrera

Consultant or advisory role: Bristol Myers Squibb, Genentech, Merck, Seagen, AstraZeneca, ADC Therapeutics, Takeda, Genmab, Pfizer, Abbvie, Allogene Therapeutics

Other remuneration: Research funding: Bristol Myers Squibb, Genentech, Merck, Seagen, AstraZeneca