Real-World Outcomes of Frontline Polatuzumab and Impact of Frailty in Older Adults with Newly Diagnosed Diffuse Large B-Cell Lymphoma (DLBCL)

Introduction

The FDA approval of polatuzumab with rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-RCHP) in 2023 has enriched the treatment landscape for newly diagnosed diffuse large B-cell lymphoma (DLBCL). In the phase III POLARIX trial, patients (pts) ≥ 70 years (yrs) had a lower risk of progression, relapse, and death without any increase in grade 3-5 adverse events (AEs) with pola-RCHP compared to those receiving R-CHOP (Hu et al, J Clin Oncol, 2023). While clinical trial data appear to support the risk-benefit profile of pola-RCHP in older adults (OA), there is a paucity of real-world data to validate these findings. Moreover, data on the impact of frailty on outcomes with this regimen in OA is lacking. This study seeks to fill that void and represents the largest single-center retrospective analysis of pts with DLBCL receiving frontline (1L) polatuzumab in the commercial setting to date.

Methods

Eligible pts (n=114) were identified using Memorial Sloan Kettering Cancer Center institutional databases and included all adults (age ≥ 18 yrs) who received polatuzumab in the 1L setting for DLBCL. Baseline characteristics, treatment details, toxicities, and outcomes were collected by retrospective chart review. As duration of follow up is not mature yet, complete response rate (CRR) was chosen as the primary end point for this report; secondary endpoints included overall response rate (ORR), progression free survival (PFS), overall survival (OS), and safety.

Results

A total of 114 pts with DLBCL received polatuzumab in the 1L setting (104 pola-RCHP, 2 pola-R-mini-CHP, 8 other regimens - e.g., pola-CHP without rituximab in CD20-negative DLBCL). Median age was 66 yrs (range 23-89); 34 (30%) pts were ≥ 70 yrs and 9 (8%) pts were ≥ 80 yrs. The overall population skewed male (58%) and toward non-germinal center B-cell-like (GCB) subtype DLBCL (59% vs. 35% GCB, 6% unclassifiable). A majority had stage IV disease (80%) with high International Prognostic Index (IPI) scores (IPI 3-5: 63%) and involvement of >1 extranodal site (56%). B symptoms were present in 32% of pts and CNS involvement in 2%. Eastern Cooperative Oncology Group (ECOG) status reflected a robust population (ECOG 0-1: 88%). In subgroup analysis, 59% of OA (pts ≥ 70 yrs) had non-GCB subtype DLBCL (32% GCB, 9% unclassifiable). Among OA, 5 (15%) were identified as having a geriatric syndrome (GS) (defined as the presence of dementia, delirium, depression, osteoporosis, incontinence, falls, failure to thrive, or neglect/abuse) while 3 (9%) were noted to have impairments in at least one activity of daily living (ADL) (defined as bathing, dressing, toileting, transferring, feeding, or continence).

Among all pts, ORR was 94% with CRR of 81%; 5% of pts had primary refractory disease. CRR was numerically higher in pts ≥ 70 yrs compared to those < 70 yrs (85% vs 79%), although this did not reach statistical significance (p=0.85). Similarly, ORR was higher in pts ≥ 70 yrs compared to pts < 70 yrs (97% vs 93%, p=0.67). Both pts treated with pola-R-mini-CHP remained in CR at data cutoff. In addition, OA with either geriatric syndromes (n=5) or ADL impairments (n=3) achieved encouraging ORRs and CRRs of 100%; all but 1 pt who developed grade 3 cardiomyopathy were able to complete 6 cycles of treatment. Among all pts, CRR was numerically lower in GCB vs non-GCB subtype (75% vs 82%, p=0.65), men vs women (76% vs 88%, p=0.34), IPI 3-5 vs IPI 1-2 (76% vs 88%, p=0.59), ECOG ≥2 vs ECOG 0-1 (70% vs 81%, p=0.75), and those with involvement of >1 extranodal site (73% vs 90%, p=0.09). Compilation and analysis of adverse event data is ongoing to understand rates of toxicities and factors predicting tolerability.

At a median follow up of 5.0 months (range: 0-23 months), median PFS and OS have not been reached; 19 pts have had evidence of progression of disease, and 4 pts have died (2 due to disease progression; 2 for unknown reasons). Continued follow up will allow us to analyze survival differences between various subgroups.

Conclusion

In this large retrospective analysis of polatuzumab-containing regimens for newly diagnosed DLBCL, we demonstrate robust real-world response rates in line with those reported in clinical trials. We also confirm similar efficacy of pola-RCHP in OA, even in the presence of GS or impairments in ADLs. Lastly, we advocate for prospective fitness evaluation in OA as retrospective analyses typically underestimate the prevalence of geriatric impairments.

Boardman:Cancer Study Group, LLC: Consultancy; OncLive: Honoraria; Bristol Myers Squibb: Consultancy. Epstein-Peterson:OncLive: Honoraria; Amgen: Research Funding; Viracta: Research Funding; Kymera: Research Funding; Genmab: Consultancy. Falchi:Genentech, Roche, Genmab, AbbVie, Innate, BeiGene: Research Funding; AbbVie, Genentech, ADC Therapeutics, Seagen, Ipsen: Membership on an entity's Board of Directors or advisory committees; EvolveImmune: Consultancy; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Genmab: Consultancy, Research Funding; Genentech, Roche, Genmab, Abbvie, Sanofi, EvolveImmune: Honoraria; Roche: Consultancy, Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Memorial Sloan Kettering Cancer Center: Current Employment; Kaplan: Other: CME Presentation: Projects in Knowledge; Taylor Francis: Other: Journal Editor; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Kumar:Kite Pharmaceuticals, Janssen: Honoraria; Seattle Genetics: Research Funding; Abbvie Pharmaceuticals: Research Funding; Adaptive Biotechnologies, Celgene, Pharmacyclics: Research Funding; Astra Zeneca: Honoraria, Research Funding; Genentech, Inc.: Consultancy, Honoraria, Research Funding; BridgeBio Pharmaceuticals: Current equity holder in publicly-traded company; Loxo Oncology/Lily Pharmaceuticals: Honoraria, Research Funding. Lue:Kymera Therapeutics: Research Funding; ADC Therapeutics: Consultancy; GenMab: Consultancy; Merck Pharmaceuticals: Consultancy; Lumanity: Consultancy. Horwitz:ADC Therapeutics, Affimed, Celgene, Crispr Therapeutics, Daiichi Sankyo, Kyowa Hakko Kirin, Takeda, Seattle Genetics, Trillium Therapeutics, and SecuraBio.: Research Funding; Auxilius Pharma, Abcuro Inc., Corvus, Daiichi Sankyo, DrenBio, Farallon Capital Management, L.L.C., Kyowa Hakko Kirin, March Bio, Neovii Pharmaceuticals AG, ONO Pharmaceuticals, Pfizer, SecuraBio, SymBio, Treeline Bio and Takeda Pharmaceuticals.: Consultancy; Auxilius Pharma, Abcuro Inc., Corvus, CTI BioPharma Corp, Daiichi Sankyo, DrenBio, Kyowa Hakko Kirin, March Bio, ONO Pharmaceuticals, Pfizer, SecuraBio, SymBio and Takeda Pharmaceuticals.: Honoraria. Johnson:BioNTech: Consultancy; Sobi: Other: Advisory Board; Electra Therapeutics: Other: Advisory Board. Moskowitz:Miragen Therapeutics: Honoraria; ADC therapeutics: Research Funding; Merck: Research Funding; Seattle Genetics: Honoraria, Research Funding; Secura Bio: Research Funding; Takeda Therapeutics: Honoraria; Tessa Therapeutics: Honoraria; Incyte: Research Funding; Brystal-Meyers Squibb: Research Funding; Beigene: Research Funding. Noy:AstraZeneca: Consultancy; epizyme: Consultancy; guidepoint global: Consultancy; clearview: Consultancy; EUSA: Consultancy; health advance: Consultancy; janssen Global: Consultancy, Other: drug provided for research; ADC therapeutics: Consultancy; Beigene: Consultancy; Medallion Healthcare: Honoraria; NSCI: Honoraria; OncLIve: Honoraria; PER: Honoraria; Cornerstone Pharma: Honoraria, Research Funding. Palomba:Novartis: Consultancy; Synthekine: Consultancy; Bristo Meyer Squibb: Consultancy; Cellectar: Consultancy. Steiner:Seagen: Research Funding; BMS: Research Funding; Rafael Pharmaceuticals: Research Funding; GSK: Research Funding. Stuver:Pfizer: Research Funding. Zelenetz:Genentech/Roche: Consultancy, Research Funding; Novartis: Consultancy; BeiGene: Consultancy, Research Funding; BMS/Celgene/Juno: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnology: Consultancy; Janssen: Consultancy; Gilead/Kite: Consultancy; Abbvie: Consultancy; MorphoSys: Consultancy; AstraZeneca: Consultancy; MEI Pharma: Consultancy, Research Funding. Salles:Incyte: Consultancy; Ipsen: Consultancy, Research Funding; Merck: Consultancy; Molecular Partners: Consultancy; AbbVie: Consultancy, Research Funding; Genmab: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Genentech/Roche: Consultancy, Research Funding; BeiGene: Consultancy; BMS/Celgene: Consultancy; Kite/Gilead: Consultancy; Nurix: Research Funding. Torka:Seagen: Consultancy; Genmab: Consultancy; TG Therapeutics: Consultancy; ADC Therapeutics: Consultancy; Abbvie: Consultancy; Lilly Oncology: Consultancy; Genentech: Consultancy.