Laboratory Prognostic Index (LaPI) in Diffuse Large B Cell Lymphoma: Validation Study on Behalf of the Spanish Lymphoma Cooperative Group (GEL-TAMO)

Introduction: A large number of prognostic variables has been described in diffuse large B cell lymphoma (DLBCL), but not all of them are available in all centres. In the 2021 ASH Annual Meeting and Exposition the LaPI score (Laboratory Prognostic Index) was presented; this tool included three laboratory variables at DLBCL diagnosis: lactate dehydrogenase (LDH), hemoglobin (Hb), and beta-2 microglobulin (B2M). The aim of this work is to optimize the LaPI score design and to validate this index in an independent cohort of DLBCL patients.

Methods: The training cohort was composed of 125 DLBCL NOS cases with a large blood test performed at diagnosis; more than thirty variables were studied. The laboratory parameters with the highest prognostic impact on event-free survival (EFS) were selected by univariate hazard ratio analysis (UV HR, Cox regression). B coefficients obtained by multivariate (MV) analysis were used to assign the score of each variable. The LaPI score was also applied to overall survival (OS). For the validation of the index there was used the GELTAMO-IPI cohort (N=828). The parameters' cut-offs were established according to each Laboratory range. After combining both cohorts, patients were finally grouped according to their EFS. The LaPI score was compared with other DLBCL prognostic indexes by Kaplan Meir curves and by the concordance C-index.

Results: The training cohort (median follow-up 24 months, range 0.3-109) included patients with both a curative- (85%) and a non-curative- (15%) -intention therapy. The three variables included in the final LaPI model were: high LDH level (EFS UV HR 2.4, MV B coefficient 0.5, 1 point), anaemia (EFS UV HR 3.1, MV B coefficient 0.5, 1 point), and high B2M level (increased to less than double: EFS UV HR 2.6, MV B coefficient 0.6, 1 point; increased to more than double: EFS UV 3.1, MV B coefficient 0.9, 2 points). The patients of the validation cohort (median follow-up 46 months, range 1-162) had completed a first-line treatment based on R-CHOP and a minimum one-year follow-up. After combining both cohorts, a 953 patient-series was obtained, with a 64-year-old median age (18-91 range), a male/female ratio close to 1, and a median follow-up of 41 months. The LaPI score was applied to this new cohort (Figure 1) and the differences in EFS between each score level and the immediately higher level were evaluated (UV HR, 95% CI): 0 vs 1 point HR 2.3 (1.3-4.1), 1 vs 2 points HR 1.1 (0.8-1.6), 2 vs 3 HR 1.7 points (1.2-2.4) and 3 vs 4 HR 2.2 points (1.4-3.3). Patients with a score of 1 and 2 were grouped into a single cluster. The R-IPI score was also calculated: the very good group (9%) presented a 97% 3-year EFS and a 97% 3-year OS, the good group (46%) 80% EFS and 86% OS after 3 years, and the poor group (45%) 60% 3-year EFS and 63% 3-year OS.

Conclusions: The LaPI score is able to predict survival at DLBCL diagnosis by the analysis of three laboratory parameters routinely assessed in peripheral blood in most centres: LDH, Hb and B2M. Its prognostic discrimination power is superior to other scores, its application is easier than any other index, and it is capable of identifying a group of patients with a very adverse prognosis for whom it would be necessary to identify optimized therapeutic strategies.

Salar:Janssen: Honoraria, Speakers Bureau; BMS/Celgene: Honoraria; Beigene: Honoraria; Roche: Research Funding, Speakers Bureau; Abbvie: Research Funding; Incyte: Speakers Bureau; Gilead: Research Funding. Cordoba:Janssen: Consultancy; Astra Zeneca: Consultancy; Beigene: Consultancy; Lilly: Consultancy; Astra Zeneca: Other: Speaker; Janssen: Other: Speaker. Novelli:Novartis: Research Funding; Mundipharma: Consultancy. González de Villambrosia:Takeda: Honoraria; Janssen: Honoraria; Incyte: Honoraria; EusaPharma: Honoraria. Sancho:Bristol Myers Squibb: Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Kern Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees; Eli Lilly & Company: Consultancy, Membership on an entity's Board of Directors or advisory committees; Miltenyi Biomedicine: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sandoz: Consultancy, Membership on an entity's Board of Directors or advisory committees. Abrisqueta:Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sandoz: Honoraria; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees. Martín García-Sancho:Kyowa Kirin: Consultancy, Honoraria, Other: Support for attending meetings and/or travel; Clinigen: Consultancy, Honoraria, Other: Support for attending meetings and/or travel; Eusa Pharma: Consultancy, Honoraria, Other: Support for attending meetings and/or travel; Roche: Consultancy, Honoraria, Other: Support for attending meetings and/or travel; Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Other: Support for attending meetings and/or travel; Novartis: Consultancy, Honoraria, Other: Support for attending meetings and/or travel; Gilead/Kite: Consultancy, Honoraria, Other: Support for attending meetings and/or travel; Servier: Consultancy, Honoraria, Other: Support for attending meetings and/or travel; Incyte: Consultancy, Other: Support for attending meetings and/or travel; Lilly: Consultancy, Other: Support for attending meetings and/or travel; Takeda: Consultancy, Honoraria, Other: Support for attending meetings and/or travel; ADC Therapeutics America: Consultancy, Honoraria, Other: Support for attending meetings and/or travel; Miltenyi: Consultancy, Honoraria, Other: Support for attending meetings and/or travel; Kern: Consultancy, Honoraria, Other: Support for attending meetings and/or travel. Bastos-Oreiro:KITE/GILEAD: Consultancy, Honoraria; NOVARTIS: Speakers Bureau; INCYTE: Consultancy, Speakers Bureau; JANSSEN: Speakers Bureau; Roche: Consultancy, Research Funding, Speakers Bureau.