Real-World Outcomes of Frontline Polatuzumab and Impact of Frailty in Older Adults with Newly Diagnosed Diffuse Large B-Cell Lymphoma (DLBCL)
Authors: Iyengar Varun , Chicola Jessica , Joseph Ashlee , Okwali Michelle , Truong Regina , Bapodra Neil , Boardman Alexander P. , Caron Philip , David Kevin A. , Epstein-Peterson Zachary D. , Falchi Lorenzo , Ghione Paola , Kumar Anita , Lue Jennifer Kimberly , Luttwak Efrat , Horwitz Steven , Intlekofer Andrew M. , Johnson William T. , Moskowitz Alison , Noy Ariela , Owens Colette , Palomba Maria Lia , Steiner Raphael E. , Stuver Robert , Vardhana Santosha A. , Zelenetz Andrew D. , Salles Gilles , Hamlin Paul A. , Torka Pallawi 
Published: December 2024

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 &gt;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 &lt; 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 &lt; 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 &gt;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.