Identification of a clinicopathologic prognostic index for newly diagnosed large B-cell lymphoma patients treated with R-CHOP

Identification of a clinicopathologic prognostic index for newly diagnosed large B-cell lymphoma patients treated with R-CHOPWhile the International Prognostic Index (IPI), 1 as well as the revised IPI (R-IPI), 2 are predictive of survival outcomes in newly diagnosed large B-cell lymphoma (LBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), differences in survival outcomes may also be explained by heterogeneity of tumor features.Results from assays performed in clinical laboratories can identify pathologic subgroups of LBCL with an unfavorable prognosis following treatment with R-CHOP, including non-germinal center B (GCB) cell of origin, 3 MYC rearrangement, 4,5 double-hit, 6,7 double-expressor 8,9 and TP53 mutation. 10,11However, tumor features have not been routinely incorporated into a prognostic index for patients with newly diagnosed LBCL treated with R-CHOP.Through analysis of features of LBCL tumors obtained from newly diagnosed LBCL patients treated with R-CHOP, we developed a novel Clinicopathologic Prognostic Index (CPPI), which outperformed the R-IPI in identifying a smaller cohort of patients who experienced inferior survival outcomes.The CPPI may be useful in risk-stratifying newly diagnosed LBCL patients receiving standard-of-care therapies and identifying high-risk patients who may benefit from treatment with investigational regimens.Clinicopathologic data from eligible newly diagnosed LBCL patients obtained from three publicly available datasets 12,14 were retrospectively compiled and analyzed.Included patients were those treated with R-CHOP with available International Prognostic Index (IPI) score, cell of origin (COO) and double expressor (DE) status (MYC 40% and BCL2 50%) by immunohistochemistry (IHC), MYC rearrangement and MYC-BCL2 double-hit status by fluorescence in situ hybridization (FISH), genomic variant reporting of TP53 and follow-up time of over 1 year from diagnosis if not experiencing disease progression before that time.Excluded patients were those whose tumors demonstrated MYC-BCL2 double-hit status as they are not routinely treated with R-CHOP in clinical practice.TP53 mutations were classified as loss of function (LOF) as previously described, 12 defined as either as a missense mutation designated as non-functional and/or LOF via query of the TP53 Database or any nonsense, frameshift, or splice site mutation as per ClinVar and/or PVS1 criteria for predicted LOF variants, and only those classified as LOF were included in the analysis.Progression-free survival (PFS) was determined from diagnosis to documented disease progression, death from any cause or date of last follow-up in remission.Overall survival (OS) was calculated from the date of diagnosis until