Efficacy of Tagraxofusp in Blastic Plasmacytoid Dendritic Cell Neoplasm, an Interrupted Time Series Analysis

Introduction: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare neoplasm that usually affects older adults with a median age of 66. ALL or AML induction regimens have been used to treat BPCN for many years. Tagraxofusp received FDA approval in December 2018 after showing a 75% complete response rate in the upfront setting and 67% in the relapsed setting based on a noncomparative phase II clinical trial. There is a paucity of real-world data on its efficacy.

Methods:

We identified the patients with BPDCN using the Surveillance Epidemiology and Results Database (SEER) database between 2000 and 2021. We calculated each year's mortality incidence rate (MIR) by summing the number of deaths for patients diagnosed with BPDCN each year over their total follow-up time in months. Data was grouped by age categories, sex, race, and year of diagnosis. To accurately estimate the efficacy of Tagraxofusp on overall survival, we chose 1000 randomly selected acute myeloid leukemia patients from the SEER database and used them as a comparator group. AML data was grouped, and MIR was calculated similarly to the BPDCN dataset. Both data were combined. We used an interrupted time series model using the Non-linear mixed effect model package in R to evaluate the difference in MIR before and after 2019 (2015-2019 and from 2019-2021) using AML patients as a comparator group. The year 2019 was used because it is the year when Tagraxofusp was available in the market. . Survival probabilities were estimated using the Kaplan-Meier method, with differences assessed by the log-rank test.

Results: We identified 638 patients with BPDCN in the SEER database between 2000-2021. Only 87 patients (13.6%) were diagnosed after 2019. The median age of the participants was 60 years old (IQR 35-73). 84% were males, and most were white (85%). The median survival was 25 months (0.95 CI 21-31 months). Median overall survival (OS) significantly decreased with age, with a median OS of 11 months (0.95 CI 9-14) and 24 months (0.95 CI 19-45) for those above the age of 70 and between 60-70 years old compared to 63 months (0.95 CI 18-113) for those between 50-60 years-old (P<0.01). There was no difference in median OS between White and non-White ethnic groups (25 months (0.95 CI 21-32) vs 19 months (0.95 CI 15-45), P= 0.79). Females tend to have higher median OS compared to males (37 months (0.95 CI 25-47) vs 23 months (095 CI 19-27) with a P value of 0.078.

There was no difference in OS among patients with BPDCN diagnosed between 2010-2015,2015-2018 and 2019-2021, with a median OS of 18 months (0.95 CI 13-46), 23 months (0.95 CI 16-38), and 16 months (0.95 CI 9-24) (P=0.33). Similarly, there was no difference in OS across the same year groups among AML sample patients with a median OS of 7 months (0.95 CI 6-11), eight months (0.95 CI 6-10), and eight months (0.95 CI 6-12) (P=0.63).

In the interrupted time series model that considers the randomly selected 1000 AML patients as a comparator group. patients who had BPDCN after 2019 had numerically lower absolute values of MIR compared to AML patients (-10.2%). However, the P value was not significant. Also, it was not significant for the trend post-Tagraxofusp approval (0.018, P=0.8).

Conclusion

In this interrupted time series analysis, we found that Tagraxofusp use was associated with a drop in MIR. However, this was not statistically significant. This could be due to limited size or due to non-superiority to other regimens used in the pre-Tagraxofusp era. Further research is needed to determine the efficacy of Tagraxofusp in the real-world.

Iragavarapu:Celgene/BMS: Research Funding; Morphosys/incyte: Research Funding; Regeneron: Research Funding; Century Therapeutics: Research Funding; Kite/Gilead: Research Funding; Merck: Research Funding; Janssen: Research Funding.