Evaluating the role of molecular markers in predicting relapse and guiding cost-effective surveillance strategies in low-grade non-Hodgkin lymphomas.

20 Background: Follicular Lymphoma (FL) is the most common indolent Non-Hodgkin Lymphoma. With newer therapies, outcomes have improved with only 10-20% now having early relapses. Clinical prognostic models however have limitations in predicting these relapses. Newer models involving molecular markers including PRIMA23 and m7-FLIPI have better predictive potential for early relapse. Over 10 molecular and genetic markers are uniquely present in patients who suffer an early relapse. A focused surveillance using molecular and genetic markers could therefore provide better cost-effective surveillance strategies in FL. Methods: Data on molecular and genetic signatures of de-novo and relapsed FL were collected from PUBMED and EMBASE databases. Searches were conducted in accordance with the National Institute for Health and Care Excellence guidelines. Eligible studies were those limited to adults ≥18 years with FL undergoing initial chemo-immunotherapy and those that relapsed within 2 years. Cost of PET-CTs was extracted from Medicare and private insurance billing data. Results: In the United States,13,619 FL cases will be diagnosed in 2025. Clinical surveillance in FL currently involves CT or PET- CT scans every 4 months. Over a 2-year period 27,238 patients will complete 163,428 PET-CT’s. The national average Medicare cost of a PET-CT is $1599. With private insurance, cost is $2550 to $7275. The total 2-year outlay for PET-CT’s therefore range from $261 to $416 million without factoring ancillary costs. Over a 10-year period, this amounts to $1.3- 2.0 billion. These costs could be reduced by limiting surveillance to patients at higher risk for relapse. In an Alliance Group study, only 15.2% of patients with FL were high-risk using m7-FLIPI model indicating that selecting high-risk patients for image-based surveillance can reduce surveillance costs by 80-90%. Conclusions: Several unique molecular and genetic signatures are present in early relapsing patients. These include KMT2C, TP53, BTG1, MKI67, XBP1, SOCS1, B2M, FAS, IKZF3, and MYD88. 80% of early relapsing patients carry low frequency of these mutations suggesting that progression is from treatment-resistant clones existing at diagnosis. This in turn allows prognostic models like m7-FLIPI to better define high-risk patients more likely to relapse. Since this group could be as low as 10% of patients with FL, it could translate to >90% cost savings over current expenditures with targeted surveillance.