Transparency Submission

Brown, Krystal

krystal.brown@foresight-dx.com

2038082436_____

08/09/2024

Company: Foresight Diagnostics

Guideline: B-Cell Lymphomas

Panel: B-Cell Lymphomas Panel

Algorithm Page Number: BCEL-9

Specific Change Requested:

We would like to request that the Diffuse Large B-Cell Lymphoma guidelines include circulating tumor DNA minimal residual disease (ctDNA-MRD) assessment using the Foresight CLARITYTM MRD test, based on PhasED-Seq technology.

Specifically, we request the addition of ctDNA-MRD assessment using Foresight’s MRD test during follow-up for relapse or refractory disease.

- BCEL-9: In addition to Clinical and Imaging follow-up, add Molecular follow-up with ctDNA-MRD assessment during FOLLOW-UP.

FDA Clearance: N/A

Rationale for Requested Change: The body of evidence demonstrating that the prognostic performance of Foresight’s MRD test, based on PhasED-Seq technology, is superior to current standard of care PET imaging in LBCL has continued to grow over the last 5 years. With known limitations in prognostic performance of PET-CT scans, we believe the evidence collectively supports the clinical adoption of testing as part of follow-up after treatment in relapse and refractory disease. Published data across numerous manuscripts and presentations has demonstrated the prognostic performance of Foresight’s MRD test using PhasED-Seq-technology in LBCL [2-11]. Recent publications have demonstrated the prognostic performance of Foresight’s MRD test after treatment for relapsed or refractory disease [4, 10], such that it would be clinically appropriate to incorporate ctDNA-MRD into response assessment at the end of >1L therapy as well. This includes data from the multi-center Phase 3 TRANSFORM study in patients receiving the CAR19 T-cell liso-cel that demonstrates the prognostic value of Foresight’s ctDNA-MRD test in patients during the time of PET CR. Specifically, Stepan et al. showed that ctDNA-MRD status was significantly prognostic for PFS in patients in a metabolic CR both 1 month and 12 months after CAR-T infusion [reference 10, slide 12]. The analytical performance of Foresight’s MRD test has also been demonstrated to be robust and reproducible with an analytical limit of detection below 1 in 1,000,000 and a false positive rate of less than 1% [1]. Though there are many emerging MRD tests in lymphoma, only Foresight’s ctDNA-MRD test has demonstrated the robust analytical [1] and clinical validity [2-11] necessary to support clinical use. Collectively, we believe this data demonstrates that the Foresight CLARITY test provides robust and reliable results for clinical use. The consistent, superior performance of Foresight’s MRD test compared to standard of care PET-CT overall and in patients with relapse/refractory supports the use of ctDNA-MRD assessment in follow-up for relapse/refractory disease.

Citation of Literature

1. Boehm N, Close S, Kurtz DM, et al. Analytical Validation of a Circulating Tumor DNA Assay using PhasED-Seq Technology for Detecting Residual Disease in B-Cell Malignancies. medRxiv. 2024

2. Goldstein J, Kim WS, Yoon SE, et al. Optimizing Circulating Tumor DNA Limits of Detection for DLBCL during First Line Therapy. Blood. 2023;142(Supplement 1):187-187.

3. Hoffmann MS, Munoz JL, Westin J, et al. Golcadomide (GOLCA; CC-99282), a Novel CELMoD Agent, Plus R-CHOP in Patients (pts) with Previously Untreated Aggressive B-Cell Lymphoma (a-BCL): Safety and Efficacy Results from Phase 1b Dose Expansion. Blood. 2023;142(Supplement 1):4459-4459.

4. Kurtz DM, Hogan G, Schultz A, et al. Early and Sustained Circulating Tumor DNA Response Dynamics after Loncastuximab Tesirine for Relapsed/Refractory Diffuse Large B-Cell Lymphoma. Blood. 2023;142(Supplement 1):3133-3133.

5. Kurtz DM, Soo J, Co Ting Keh L, et al. Enhanced detection of minimal residual disease by targeted sequencing of phased variants in circulating tumor DNA. Nature Biotechnology. 2021/12/01 2021;39(12):1537-1547.

6. Lynch RC, Poh C, Ujjani CS, et al. Polatuzumab vedotin with infusional chemotherapy for untreated aggressive B-cell non-Hodgkin lymphomas. Blood Advances. 2023;7(11):2449-2458.

7. Roschewski M, Kurtz DM, Westin J, et al. MRD-NEGATIVITY AFTER FRONTLINE DLBCL THERAPY: POOLED ANALYSIS OF 6 CLINICAL TRIALS. Hematological Oncology. 2023;41(S2):177-179.

8. Roschewski M, Kurtz DM, Westin J, et al. MRD-Negativity As a Potential Surrogate Endpoint after Frontline DLBCL Therapy: Pooled Analysis of Trials & Implications for Clinical Trial Design. Blood. 2022;140(Supplement 1):785-786.

9. Roschewski M, Lindenberg L, Mena E, et al. End-of-Treatment Response Assessment after Frontline Therapy for Aggressive B-Cell Lymphoma: Landmark Comparison of a Singular PET/CT Scan Versus Ultrasensitive Circulating Tumor DNA. Blood. 2023;142(Supplement 1):192-192.

10. Stepan L, Ansari S, Okal A, et al. Circulating Tumor DNA Dynamics as Early Outcome Predictors for Lisocabtagene Maraleucel as Second-Line Therapy for Large B-Cell Lymphoma from the Phase 3 TRANSFORM Study. Blood. 2023;142(Supplement 1):225-225.

11. Sworder BJ, Yoon SE, Kim SJ, et al. Prognostic Utility of Minimal Residual Disease (MRD) after Curative Intent Induction Therapy for DLBCL: A Prospective Real-World Ctdna Study. Blood. 2023;142(Supplement 1):69-69.