Validation of the NCCN‐IPI for diffuse large B‐cell lymphoma (DLBCL): the addition of β₂‐microglobulin yields a more accurate GELTAMO‐IPI

Abstract

The study included 1848 diffuse large B-cell lymphoma (DLBCL)patients treated with chemotherapy/rituximab. The aims were to validate the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) and explore the effect of adding high Beta-2 microglobulin (β2M), primary extranodal presentation and intense treatment to the NCCN-IPI variables in order to develop an improved index. Comparing survival curves, NCCN-IPI discriminated better than IPI, separating four risk groups with 5-year overall survival rates of 93%, 83%, 67% and 49%, but failing to identify a true high-risk population. For the second aim the series was split into training and validation cohorts: in the former the multivariate model identified age, lactate dehydrogenase, Eastern Cooperative Oncology Group performance status, Stage III-IV, and β2M as independently significant, whereas the NCCN-IPI-selected extranodal sites, primary extranodal presentation and intense treatments were not. These results were confirmed in the validation cohort. The Grupo Español de Linfomas/Trasplante de Médula ósea (GELTAMO)-IPI developed here, with 7 points, significantly separated four risk groups (0, 1-3, 4 or ≥5 points) with 11%, 58%, 17% and 14% of patients, and 5-year overall survival rates of 93%, 79%, 66% and 39%, respectively. In the comparison GELTAMO IPI discriminated better than the NCCN-IPI. In conclusion, GELTAMO-IPI is more accurate than the NCCN-IPI and has statistical and practical advantages in that the better discrimination identifies an authentic high-risk group and is not influenced by primary extranodal presentation or treatments of different intensity.

New prognosis score including absolute lymphocyte/monocyte ratio, red blood cell distribution width and beta‐2 microglobulin in patients with diffuse large B‐cell lymphoma treated with R‐CHOP: Spanish Lymphoma Group Experience (GELTAMO)

“…With the new model, the highest‐risk group had five‐year PFS of 19% and five‐year OS of 24%, favourable compared with IPI (45% and 59%, respectively). Likewise, a better high‐risk assessment of the new score was observed when compared to previously reported scores such as Tumor Score (TS), NCCN‐IPI and GELTAMO‐IPI (Rodriguez et al ., ; Zhou et al ., ; Montalbán et al ., ), which showed higher five‐year PFS and five‐year OS (32%, 38%, 29% and 45%, 46%, 40% respectively).…”

“…The NCCN‐IPI, compared with the IPI, incorporates age and LDH, achieving an enhanced capacity to discriminate low‐ and high‐risk groups (Zhou et al ., ; El‐Galaly et al ., ). With the same aim, our group recently reported the GELTAMO‐IPI, including all variables of IPI, with a further categorization of age and ECOG‐PS, as well as B2M (Montalbán et al ., ). In 1992, the MD Anderson Cancer Centre reported the TS exclusively considering variables related to the tumour: high LDH, Ann Arbor stage III/IV, high B2M, bulky mass and the presence of B symptoms (Rodriguez et al ., ).…”

“…The files of 2156 patients with DLBCL were retrieved from the archives of 20 academic and community hospitals in the GELTAMO network in Spain that was used for the validation of NCCN‐IPI and development of the GELTAMO‐IPI, as previously described (Montalbán et al ., ). Patients were diagnosed between January 1998 and July 2014.…”

Extranodal Diffuse Large B Cell Lymphoma: Molecular Features, Prognosis, and Risk of Central Nervous System Recurrence

“…The enhanced IPI (which improved on the specification of age and lactate dehydrogenase [LDH] as non-binary variables) has identified involvement of CNS, liver/gastrointestinal (GI) tract, lung, or marrow as additional unfavorable prognostic factors [9]. The Spanish Lymphoma Study Group evaluated extranodal origin in addition to the IPI, and found no additive prognostic value, but specific anatomic sites were not distinguished [13]. In contrast, a Danish-Canadian series of 443 patients staged with positron emission tomography (PET) found that 67% had extranodal involvement, that PET uptake in bone/bone marrow, pleura, or female reproductive organs was independently associated with worse progression-free survival (PFS) and OS, and that >2 or >3 involved sites conferred progressively worse prognosis [3].…”

Spanish Lymphoma Group (GELTAMO) guidelines for the diagnosis, staging, treatment, and follow-up of diffuse large B-cell lymphoma

“…Further independent studies are required to validate the proposed greater effectiveness of newer indices, including the National Comprehensive Cancer Network (NCCN)-IPI and GELTAMO-IPI [16, 17]. The inclusion of biomarkers and genes implicated in the biology of DLBCL has not significantly improved the prognostic accuracy of the IPI [18, 19].…”