Hamadani M, Graham C, Liao L, Zhang K, Strat HM, Ungar D, Ai W, Chen L, Carlo-Stella C. Long-term survival projections of loncastuximab tesirine-treated patients in relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). J Clin Oncol. 2022 Jun.


BACKGROUND: Loncastuximab tesirine (loncastuximab tesirine-lpyl; Lonca) is an FDA approved CD19-directed antibody-drug conjugate for R/R DLBCL. From the LOTIS-2 trial primary data cut (April 6, 2020), overall response rate was 48.3% and median overall survival (OS) was 9.9 months. The OS Kaplan-Meier (KM) plot displayed a survival plateau suggesting the presence of long-term survivors (LTS). Survival analyses were conducted on a more mature data cut (March 1, 2021; median follow-up = 1.7 years, follow-up completeness at median = 81%) to estimate the percentage of LTS and expected lifetime survival (mean OS) for lonca-treated patients.

METHODS: Consistent with studies of other R/R DLBCL treatments, identified through a literature review, parametric and mixture cure models were fit utilizing multiple distributions. Flexible cubic spline (hazard scale 1-3 knots) and non-mixture cure analyses were also conducted. Age- and gender-matched United States life table hazards were used in projections for LTS and to ensure modeled hazards were not less than the general population. Best-fit models were determined through fit statistics, KM and fitted curve overlays, and clinical plausibility. The best-fit model from each method was a candidate for overall best fit. A hybrid model following the best-fit parametric/spline model to a defined time point and switching to general population mortality was also constructed.

RESULTS: Mixture and non-mixture cure models fit best (individual best fits gamma and Weibull, respectively). Parametric and spline models (individual best fits log-normal and 2 knot models, respectively) did not fit the observed data well nor fit the clinical expectation of long-term survival. Due to better fit, spline models were used in the hybrid model. LTS from the mixture cure and non-mixture cure models were 24-26%. Mixture cure, non-mixture cure, and hybrid model with a 2-year switch point were consistent in survival predictions (6.11-6.23 years). In a sensitivity analysis with 3-year switch point in the hybrid model, the estimated survival was shorter due to the switch point being below the observed survival plateau. Table 1 presents full survival results and fit statistics.

CONCLUSIONS: The observed survival plateau suggests lonca-treated patients may include LTS. Mixture cure, non-mixture cure, and hybrid models fit the trial data well and align on survival projections (6.11-6.23 years). Additional follow-up may help refine the switch point of the hybrid model and confirm presence of LTS.

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