Abstract 1440: Evolution of CD19 expression in pediatric B-cell malignancies in the era of targeted therapy
Authors: Libert Diane , Yuan Constance M. , Shalabi Haneen , Salem Dalia , Yates Bonnie , Delbrook Cindy , Fry Terry , Shern John , Stetler-Stevenson Maryalice , Shah Nirali 
Published: August 2019

Introduction: Ubiquitous expression of CD19 renders it an ideal target for immunotherapy in B-cell neoplasms. As such, loss or decrease in CD19 is emerging as a means of cancer resistance. As a referral center for CD22-based approaches, an alternative target in B-cells, we had the opportunity to serially evaluate CD19 changes following targeted therapy.

Methods: In this retrospective chart review, we assessed for evolution of CD19 expression in patients referred for CD22 immunotherapies. Data collection included demographics, prior therapies, and serial CD19 expression as assessed by flow cytometry (% positivity and site density), response to prior CD19 targeted therapy, and change from baseline.

Results: 56 unique patients were analyzed. The median age was 19 years (range 4-30). At the time of referral (baseline), 23 (41%) subjects were CD19 negative, all following &gt; 1 forms of CD19-targeted therapy. 8 (14%) were CD19 partial positive including 2 patients who were 28% and 81% CD19 positive but CD19-immunotherapy naïve. 25 (43%) were CD19 positive, 2 were CD19 dim following blinatumomab, and 7 were CD19-immunotherapy naïve. In 40 of 56 subjects (71%), there was no change in CD19 expression. 16 (29%) patients had either gain or loss of CD19. In those with CD19 re-expression, the median time for this occurrence was 91 days from baseline.

Conclusions: In this heterogenous population, we document evolution in CD19 expression following CD19-immunotherapy and identified unique patients with inherent CD19 alterations. Some patients retain or regain CD19 expression, conferring new susceptibility to CD19 targeting, while others permanently lose CD19, rendering further CD19-targeted approaches futile. The development of this latter population raises the concern for the outgrowth of subclinical CD19 negative clones. Pairing these findings with genomics will be important to understand the mechanism behind these changes in expression in the search to optimize treatment for B-cell cancers.

Table 1Baseline DemographicsFirst Change from Baselinen=56 (%)# with CR to prior therapyChangen (%)Days to ↑ CD19 expression (Median, IQR)Age (median, range in years)19 (4-30)Male38 (68%)At study baseline*CD19 negative23 (41%)Baseline CD19 Negative (n=23)Remains CD19 neg17 (74%)NAPrior CD19 CAR1614Prior blinatumomab32Becomes CD19 Partial4 (17%)133 (351)Both33**Other CD19 targeted (SGN19a)10Becomes CD19 Positive2 (9%)416 (39)No prior targeted therapy0–CD19 partial#8 (14%)Baseline CD19 Partial (n=8)Becomes CD19 neg0NAPrior CD19 CAR10Prior blinatumomab62Remains CD19 partial4 (50%)NABoth00Becomes CD19 positive4 (50%)53 (66)No prior targeted therapy2–CD19 positive23 (41%)Baseline CD19 positive (n=25)Becomes CD19 neg##2 (8%)NAPrior CD19 CAR55Prior blinatumomab74Becomes CD19 partial3 (12%)NABoth42**No prior targeted therapy7–CD19 dim^ (uniformly positive)2 (4%)CD19 dim to positive1 (4%)21 (NA)Prior CD19 CAR00Prior blinatumomab21Remains CD19 positive19 (76%)NABoth00No prior targeted therapy00CR: Complete remissionIQR: interquartile range*Baseline represents first sample that subject had at the time of referral to the NIH with detectable disease^Indicates CD19 expression &lt; 2000 sites/cells#Partial positivity defined by &lt; 95% antigen positive**Complete response to CD19 CAR, no response to blinatumomab##Following interval CD19 targeted-therapy

Citation Format: Diane Libert, Constance M. Yuan, Haneen Shalabi, Dalia Salem, Bonnie Yates, Cindy Delbrook, Terry Fry, John Shern, Maryalice Stetler-Stevenson, Nirali Shah. Evolution of CD19 expression in pediatric B-cell malignancies in the era of targeted therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1440.