Long-term survival projections of loncastuximab tesirine-treated patients in relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).

Authors

Mehdi Hamadani

Mehdi Hamadani

BMT & Cellular Therapy Program, Medical College of Wisconsin, Milwaukee, WI

Mehdi Hamadani , Christopher N. Graham , Laura Liao , Katherine H Zhang , Hannah Strat , David Ungar , Weiyun Z. Ai , Lei Chen , Carmelo Carlo-Stella

Organizations

BMT & Cellular Therapy Program, Medical College of Wisconsin, Milwaukee, WI, RTI Health Solutions, Research Triangle Park, NC, ADC Therapeutics, Inc., New Providence, NJ, Clinical Development, ADC Therapeutics America, Inc., Murray Hill, NJ, Division of Hematology and Oncology, Department of Medicine, University of California, San Francisco, CA, Humanitas Research Hospital, Rozzano, Italy

Research Funding

Pharmaceutical/Biotech Company

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 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.

Results.

Method
Distribution
Mean Survival, years
AIC
Parametric
Log-normal
1.97
238.7
Flexible cubic spline
Hazard, 2 knots
2.39
240.2
Mixture cure
Gamma
6.13
236.7
Non-mixture cure
Weibull
6.11
236.8
Hybrid flexible cubic spline
Hazard, 2 knots,2-year switch point
6.23
--
Hybrid flexible cubic spline
Hazard, 2 knots,3-year switch point
4.96
--

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Abstract Details

Meeting

2022 ASCO Annual Meeting

Session Type

Publication Only

Session Title

Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia

Track

Hematologic Malignancies

Sub Track

Non-Hodgkin Lymphoma

Citation

J Clin Oncol 40, 2022 (suppl 16; abstr e19551)

DOI

10.1200/JCO.2022.40.16_suppl.e19551

Abstract #

e19551

Abstract Disclosures