Defining Primary Refractory Diffuse Large B‐cell Lymphoma (DLBCL) Based on Survival Outcomes

Abstract

Background: DLBCL that fails to achieve a complete response (CR) or relapses early after standard immunochemotherapy (IC, e.g., R-CHOP or similar) is referred to as primary refractory DLBCL (prDLBCL) and has a poor prognosis. Different definitions of prDLBCL have been used in literature, and it is uncertain which definition of primary refractory correlates most closely with survival outcomes. In this study, we examined the association of time to refractory status with survival outcomes in patients with prDLBCL. Methods: Adult patients diagnosed with DLBCL between 2015 and 2020 and seen at an academic center included in the lymphoma epidemiology of outcomes (LEO) cohort were included. PrDLBCL was defined as no response or progressive disease (PD) during frontline IC (primary progressive disease, PD), partial response (PR) at end of treatment (EOT PR), or relapse with 12 months after achieving CR at EOT (early relapse). Clinical characteristics, treatment and response data (by Lugano 2014 response criteria), and follow-up data were abstracted from LEO. Results: Out of 2747 DLBCL patients, 310 (11.3%) had prDLBCL, 147 with PD, 66 with EOT PR, and 97 with early relapse. No significant differences in age, gender, race, number of extranodal sites, stage, IPI, or cell of origin were found between the 3 groups. The proportion of MYC and BCL2/BCL6 rearrangements or Myc/Bcl2 double expressor was small and not different among the 3 groups. Salvage therapies were mainly platinum based high-dose chemotherapy (57%), MTX-based therapy for CNS relapse (12%), or targeted therapies (9%). Patients with PD had significantly lower CR/PR rates (19.6%/19.6%) to second line therapy compared to patients with EOT PR (32.1%/30.4%) or early relapse (50.6%/19.1%)(P < 0.001). The 2-year overall survival (OS) rate was 31% for patients with PD, which was significantly worse compared to patients with EOT PR (2-year OS 50%) or early relapse (2-year OS 58%)(P = 0.001)(Figure 1A). In patients with early relapse, the 2-year OS was not significantly different among those who relapsed within 3 months or between 3 and 6 months but appeared better for those relapsing between 6 and 12 months (Figure 1B). Our findings validate the results in our previously reported Mayo cohort, other than the survival improvement in early relapsing patients between 6 and 12 months in LEO. Keyword: Aggressive B-cell non-Hodgkin lymphoma Conflicts of interests pertinent to the abstract. Y. Wang Employment or leadership position: Merck - immediate family member Consultant or advisory role: Loxo; Incyte; Innocare; TG Therapeutics; Kite, A Gilead Company; Lilly; Janssen; BeiGene Stock ownership: Merck - immediate family member Honoraria: Kite, A Gilead Company Research funding: InnoCare; Incyte; Novartis; Genentech; Loxo; MorphoSys; Genmab M. J. Maurer Employment or leadership position: Exact Sciences - immediate family member Consultant or advisory role: Genmab; Adpative Biotechnologies Stock ownership: Exact sciences - immediate family member Research funding: MorphoSys; Bristol Myers Squibb; roche/Genentech; Genmab S. Ayyappan Consultant or advisory role: TG Therapeutics, Seattle Genetics, BeiGene, Intellisphere LLC, Fate Therapeutics, AstraZeneca Pharmaceuticals, Abbvie Research funding: Genmab, Regeneron, Genentech T. M. Habermann Consultant or advisory role: Celgene; Kite/Gilead Research funding: Genentech Other remuneration: Uncompensated: Tess Therapeutics; Loxo/Lilly; MorphoSys; Incyte; BeiGene J. R. Cerhan Consultant or advisory role: Bristol-Meyers-Squibb; Protagonist Therapeutics Research funding: NanoString Technologies; Celgene; Genentech; Genmab; Other remuneration: Uncompensated: Regeneron G. S. Nowakowski Consultant or advisory role: Celgene; MorphoSys; Genentech; Selvita; Debiopharm Group; Kite/Gilead; TG Therapeutics; Kymera; Karyopharm Therapeutics; Ryvu Therapeutics; Bantham Research funding: Celgene; NanoString Technologies; MorphoSys