Abstract 6579: Clinical utility of comprehensive genomic testing with artificial-intelligence-based analysis to identify targetable sub-clonal events in relapsed acute myeloid leukemia (AML)

Abstract

Abstract Next-generation sequencing (NGS) is increasingly used to inform diagnostic, therapeutic, and prognostic decisions in AML at the time of first presentation. We highlight the utility of NGS combined with Watson™ for Genomics (WfG), an artificial-intelligence-based decision-support system, in identifying new clinically actionable alterations as a result of clonal evolution in the relapsed disease setting. In less than 3 minutes, WfG identified an IDH1 R132H pathogenic mutation in the relapsed sample sequenced with the Illumina TruSight Tumor 170-gene panel leading to the compassionate use of ivosidenib. In addition, mutations in two genes resulting in increased sensitivity to PARP inhibitors and mutations in PTEN resulting in activation of the MTOR/PI3K signaling pathway were detected by WfG. In February 2018, a previously healthy 23-year old Caucasian female presented with AML consisting of 80% blasts with positive FLT3 mutation. She received induction cytarabine plus daunorubicin (7+3) followed by multikinase inhibitor therapy with midostaurin on days 8 to 21. A 28-day bone marrow biopsy showed persistent disease with 40% blasts. In March 2018, the patient underwent re-induction chemotherapy with mitoxantrone, etoposide, and cytarabine (MEC) followed by midostaurin on days 8 to 21. A bone marrow biopsy after completion of re-induction therapy showed complete remission with < 5% blasts (CR1). In May 2018, a matched donor was not found on a bone marrow registry, and the patient underwent a post-remission dual unrelated umbilical cord blood (UCB) hematopoietic stem cell transplantation (HSCT). Engraftment was not achieved. In July 2018, the patient had disease relapse with the presence of circulating blasts and 7% of blasts in the bone marrow. While NGS is typically not performed on relapsed samples, WfG identified IDH1 R132H and PTEN C78T pathogenic mutations using the 170-gene panel. Based on these results, the patient initiated azacytidine plus the IDH1 inhibitor ivosidenib. In August 2018, a bone marrow biopsy showed less than 5% blasts positive for a FLT3-ITD mutation. In September 2018, the patient underwent reduced-intensity conditioning with fludarabine, cyclophosphamide, and total body irradiation followed by haploidentical allogeneic HSCT from her mother. Maintenance therapy with azacytidine plus ivosidenib was continued until the present time. Currently, the patient is in remission for over 15 months without evidence of AML minimal residual disease. She has developed mild skin chronic graft-versus-host disease that is controlled with standard treatment. She works on a full-time basis and has excellent functional status. The combination of CGP, artificial intelligence, and expert care has resulted in an excellent outcome in a patient with relapsed AML. In conclusion, our experience suggests that CGP testing should be considered at different time points, at least in the relapsed setting, to help treating physicians alter or help improve clinical outcome. CGP testing in a relapsed setting is precluded because it is not covered by payers. In support of optimal care, we have initiated a new program for compassionate use of genomic testing, where such testing is medically necessary, but not covered by insurance or payer supported. Citation Format: Ravindra Kolhe, Ashis Mondal, Vamsi Kota, Nkhil Sahajpal, Meenakshi Ahluwalia, Allan Njau, Dilhan Weeraratne, Yull Arriaga, David Brotman, Gretchen Jackson, Jane Snowdon. Clinical utility of comprehensive genomic testing with artificial-intelligence-based analysis to identify targetable sub-clonal events in relapsed acute myeloid leukemia (AML) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6579.