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Patients with diffuse large B-cell lymphoma (DLBCL) who relapse within five years of frontline immunochemotherapy (IC) have very variable outcomes. In some cases, a second long-term remission can be achieved with high-dose chemotherapy and autologous stem cell transplant (auto-SCT), though patients who are refractory to therapy tend to have poor outcomes.
Being able to predict response and risk has both clinical and research applications. In December 2019, at the 61st American Society of Hematology (ASH) Meeting & Exposition, Matthew J. Maurer, Mayo Clinic, Rochester, US, presented results from a study which aimed to evaluate clinical predictors of outcome at first relapse or progression of DLBCL after frontline IC and subsequently build and validate a risk model for this patient setting.
Different cohorts were used for modeling and validation. All cohorts were formed of patients enrolled at initial diagnosis and treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) or similar IC. All patients were prospectively followed for progression or relapse:
The primary outcome measured was overall survival (OS) from date of first progression/relapse.
The final prognostic calculator was developed based on the associations between age at progression and TTP from frontline IC. The final modeling set included 1,011 patients aged 40–80 years with a TTP of 0–60 months and a concordance (C)-statistic of 0.67. When assessed for calibration using the SEAL dataset, the model predicted a mean 2-year OS of 34%, which was the same as the original 2-year OS predicted by Kaplan-Meier curves (34%).
The model was then validated with the MER and LYFO cohorts in patients who initiated second-line therapy for relapsed/refractory (R/R) DLBCL. In both the MER and LYFO cohort, the model underestimated survival, as shown in Table 1.
Table 1. Model validation in MER and LYFO cohorts
DLBCL, diffuse large B-cell lymphoma; IC, immunochemotherapy; IQR, interquartile range; LYFO, Danish National Lymphoma Registry; MER, Molecular Epidemiology Resource; OS, overall survival; R/R, relapsed/refractory |
||
|
MER cohort |
LYFO cohort |
Patient population |
Patients who initiated second-line therapy for R/R DLBCL |
Patients with DLBCL who progressed after frontline IC |
N |
290 |
559 |
Median age, years (IQR) |
62 (57–70) |
67 (60–73) |
C-statistic |
0.67 |
0.67 |
Mean 2-year OS (predicted vs actual) |
33% vs 47% |
32% vs 38% |
How can predicting survival in patients with relapsed DLBCL improve treatment decisions?
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