New Prognostic Markers Revealed in Newly Diagnosed DLBCL

Two immune systems conditions, hypogammaglobulinemia and hypocomplementemia, may be predictive of adverse outcomes in patients with diffuse large B-cell lymphoma (DLBCL), according to a retrospective study. These prognostic indicators are challenging the standard system, International Prognostic Scoring (IPI), which is a considered to be a limited measurement tool for determining patient outcomes.

The study was conducted based on earlier evidence in chronic lymphocytic leukemia (CLL), suggesting that hypogammaglobulinemia is indicative of early death, but there was no prior evidence to show the prognostic value of hypogammaglobulinemia in DLBCL. Thus, the study was launched with 553 Chinese patients with newly diagnosed DLBCL. The goal of the study was to determine how progression-free survival (PFS) and overall survival (OS) were impacted by hypogammaglobulinemia and hypocomplementemia.

Of the 533 patients enrolled, 364 were treated with rituximab (Rituxan) plus the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). A total of 161 patients with treat with the R-EPOCH regimen (rituximab plus etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin). For the remaining 28 patients, treatment was rituximab plus low-dose CHOP (R-mini-CHOP).

Patient data were stratified by the clinical characteristics obtained at baseline. In the population of patients with or without hypogammaglobulinemia, the majority of the group was male 53.0%. The majority of patients were also aged 60 years or less (56.2%), had stage III-IV disease (59.1%), presented with A symptoms (64.4%), and had an ECOG performance status of 0 or 1 (82.1%).

Laboratory tests conducted at baseline showed that the most of the study population presented with 1 or no extranodal site (74.7%), had a lactate dehydrogenase (LDH) level below upper limit of normal ([ULN], 61.5%), had an IPI score of 0-2 (69.1%), presented with a non-germinal center B-cell-likeHans classification ([B2-M]63.1%), and had a beta 2 microglobulin ≤ ULN.

It was also noted in the baseline clinical characteristics that most patients (83.9%) did not have moderate or severe infections.

The results show poor outcomes among patients with DLBCL and hypogammaglobulinemia or hypocomplementemia in terms of both PFS and OS, according to a univariate Cox regression analysis.

Overall, the hazard ratio (HR) for PFS in patients with hypogammaglobulinemia was 1.776 (95% CI, 1.264–2.495; P =.001) compared with those who did not have hypogammaglobulinemia. TheHR for OS in this comparison was 1.973 (95% CI, 1.289–3.018; P =.002). Among patients with hypocomplementemia, the HR for PFS was 1.919 ; 95% CI, 1.191–3.094; P =.007). The HR for OS was2.363; 95% CI, 1.345–4.151; P =.003).

In terms of the other clinical characteristics, PFS was significantly inferior outcomes were observed with in patients > 60 years of age compared with younger patients (HR, 1.412; 95% CI, 1.046–1.907; P =.024), in terms of patient characteristics.

Regarding disease status, B symptoms were worse compared with A symptoms (HR, 1.886; 95% CI, 1.397–2.546; P <.001), as were patients with stage III-IV disease versus early-stage-disease (HR, 3.913; 95% CI, 2.637–5.806; P <.001), an ECOG performance status > 1 compared with a high ECOG score (HR, 2.411; 95% CI, 1.728–3.365; P <.001), and more than 1 extranodal site versus multiple sites (HR, 1.937; 95% CI, 1.421–2.641; P <.001).

Comparing patients by baseline laboratory values, those with an LDH level greater than ULN had shorter PFS compared to patients with LDH lower than ULN (HR, 3.368; 85% CI, 1.468–4.596; P <.001), and those with B2-M greater than ULN versus those with B2-M lower than ULN (HR, 2.946; 95% CI, 2.120–4.094; P <.001).

Having an IPI score of 3–5 was also associated with poorer PFS in patients with DLBCL and hypogammaglobulinemia or hypocomplementemia (HR, 3.022; 95% CI, 2.236–4.085; P <.001).

The same indicators of poor PFS were indicative of significantly shorter OS in this study. For age, the HR for the being < 60 years of age versus > than 60 years was (HR,1.537; 95% CI, 1.047–2.255; P = .028. Among patients with B symptoms versus A symptoms showed the difference was demonstrated as (HR, 2.292 ; 95% CI, 1.560–3.366; P <.001). Patients with late-stage disease had worse OS compared with those with early stage disease (HR, 5.290; 95% CI , 3.013–9.289; P<.001), and those with a ECOG PS > 1 had worse OS compared with those who had a score of 0 or 1 (HR, 3.059; 95% CI, 2.016–4.641; P <.001).

Characteristics by baseline laboratory values showed poorer OS in patients with LDH > ULN versus those with LDH < ULN (HR, 3.899; 95% CI, 2.597–5.854; P <.001), as well as B2-M > ULNcompared with B2-M < ULN (HR, 4.380; 95% CI, 2.790–6.878; P <.001, and non-GCB tumors compared with GCB tumors (HR, 2.467; 1.541–3.950; P <.001).

Based on the data obtained, investigators led by Bi-Hui Pan, MD, of the First Affiliated Hospital of Nanjing Medical University, recommend that their new immunization cumulative prognostic score be utilized along with the IPI system for a more accurate prediction of survival in patients with DLBCL.

_Reference:

_{Pan BH, Kong YL, Wang L, et al. The prognostic roles of hypogammaglobulinemia and hypocomplementemia in newly diagnosed diffuse large B-cell lymphoma. Leukemia & Lymphoma. Published online Oct 16, 2020. doi: 10.1080/10428194.2020.1832673}