Pola‐R‐CHP versus R‐CHOEP in young patients with high‐risk diffuse large B‐cell lymphoma

Introduction: The best treatment for young patients with high-risk diffuse large B-cell lymphoma (DLBCL) is still a matter of debate. Results of the phase 3 R-MegaCHOEP study showed promising results using etoposide in combination with R-CHOP (R-CHOEP). Progression-free (PFS) and overall survival (OS) rates for young patients (18–60 years) with high-risk (age-adjusted IPI 2, 3) DLBCL treated with R-CHOEP were among the best reported for such patients. Recently, the combination of polatuzumab vedotin and R-CHP (pola-R-CHP) was approved for the treatment of DLBCL patients based on the data of the POLARIX study that showed an improvement of PFS following treatment with pola-R-CHP compared to R-CHOP in DLBCL patients with an IPI 2–5. To obtain further insights into the optimal treatment of young (age ≤60 years), high-risk (aaIPI 2, 3) DLBCL patients we retrospectively compared outcomes of such patients treated with pola-R-CHP or R-CHOEP. Methods: Treatment consisted of 6 cycles pola-R-CHP followed by 2 cycles of rituximab (R) given every 3 weeks or 8 cycles of CHOEP given every two weeks plus 6 cycles of R. Event-free survival (EFS), PFS, and OS of DLBCL patients ≤60 years with aaIPI 2, 3 were calculated and major toxicities compared. The Kaplan-Meier method was used to estimate EFS, PFS, and OS in each group. Hazard ratios with 95% CI and log-rank tests comparing pola-R-CHP with R-CHOEP were calculated. P-values <0.05 were considered significant. Results: 113 patients treated with pola-R-CHP and 127 patients treated with R-CHOEP were analyzed. Major patient characteristics differed in aaIPI with more patients in the R-CHOEP group showing an aaIPI of 3 (28% vs. 12%). Two-year EFS-, PFS-, and OS-rates for patients treated with pola-R-CHP were 65.9% (CI: 56.7%, 74.8%), 74.8% (66.5%, 83.0%), and 88.3% (82.3%, 94.3%) as compared to 70.5% (62.5%, 78.5%), 74.9% (67.3%, 82.6%), and 84.6% (78.3%, 91.0%) for patients treated with R-CHOEP with no significant differences for any of these endpoints between treatment regimens. Patients treated with R-CHOEP experienced more hematological toxicity and infections (29.9% ≥ grade 3 infections in R-CHOEP-treated vs. 15.0% in pola-R-CHP treated patients) with 4 treatment-related deaths occurring in patients treated with R-CHOEP and 2 treatment-related deaths following pola-R-CHP, respectively. The research was funded by: This study was sponsored by F. Hoffmann-La Roche Ltd. Keywords: Aggressive B-cell non-Hodgkin lymphoma, Combination Therapies Conflicts of interests pertinent to the abstract. G. Lenz Consultant or advisory role: F. Hoffmann-La Roche Ltd., Gilead, Janssen, Bristol-Myers Squibb, Novartis, AbbVie, Incyte, Genmab, Constellation, ADC Therapeutics, Karyopharm, Miltenyi, PentixaPharm, Sobi, Immagene, Genase, Hexal/Sandoz, Lilly Research funding: Janssen, Bayer, AstraZeneca, MorphoSys Educational grants: AbbVie, Janssen, F. Hoffmann-La Roche Ltd. Other remuneration: F. Hoffmann-La Roche Ltd., Gilead, Novartis, Takeda, Bristol-Myers Squibb, AbbVie, Incyte, ADC Therapeutics, Sobi, Hexal/Sandoz (Speaker's Bureau). F. Hoffmann-La Roche Ltd. (Expert Testimony) H. Tilly Consultant or advisory role: F. Hoffmann-La Roche Ltd., Incyte, Celgene/Bristol-Myers Squibb Honoraria: Bristol-Myers Squibb, F. Hoffmann-La Roche Ltd. Research funding: F. Hoffmann-La Roche Ltd./Genentech, Inc. Educational grants: F. Hoffmann-La Roche Ltd., Janssen M. Ziepert Research funding: F. Hoffmann-La Roche Ltd. B. Altmann Research funding: F. Hoffmann-La Roche Ltd. V. Craine Employment or leadership position: F. Hoffmann-La Roche Ltd. M. Yan Employment or leadership position: Hoffmann-La Roche Ltd. Stock ownership: Hoffmann-La Roche Ltd. C. Herbaux Honoraria: F. Hoffmann-La Roche Ltd., Janssen-Cilag, AbbVie, Gilead Sciences Research funding: Takeda Educational grants: Janssen-Cilag, AbbVie, F. Hoffmann-La Roche Ltd. M. Nickelsen Consultant or advisory role: F. Hoffmann-La Roche Ltd. Honoraria: F. Hoffmann-La Roche Ltd. J. Hirata Employment or leadership position: Genentech, Inc. Stock ownership: F. Hoffmann-La Roche Ltd. D. Sahin Employment or leadership position: F. Hoffmann-La Roche Ltd. Stock ownership: F. Hoffmann-La Roche Ltd. C. Lee Employment or leadership position: F. Hoffmann-La Roche Ltd. Stock ownership: F. Hoffmann-La Roche Ltd. F. Morschhauser Consultant or advisory role: F. Hoffmann-La Roche Ltd./Genentech, Inc., Gilead, Celgene, Bristol-Myers Squibb, AbbVie, Epizyme, Servier, AstraZeneca, Novartis, Genmab Honoraria: F. Hoffmann-La Roche Ltd./Genentech, Inc., Chugai, Eisai Other remuneration: F. Hoffmann-La Roche Ltd./Genentech, Inc. (Expert Testimony) N. Schmitz Consultant or advisory role: Allogene, Miltenyi Stock ownership: Bristol-Myers Squibb Research funding: F. Hoffmann-La Roche Ltd., Janssen Educational grants: Miltenyi, Allogene