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MEETING NEWS Highlights from the 2019 ASH Annual Meeting limited-stage disease have better overall survival (OS) than those with advanced-stage disease, they can expe- rience late relapses regardless of treatment strategy. While National Comprehensive Cancer Network guidelines recommend these patients receive abbre- viated R-CHOP followed by radiation therapy, recent research has suggested that certain patients who have a negative PET scan after 3 cycles of chemotherapy may be able to skip radiation therapy. In the S1001 study, Dr. Persky and investigators evaluated this approach in patients with newly diagnosed, stage I or II, non-bulky (< 10 cm in greatest diameter) DLBCL. Patients with CNS lymphoma, testicular lymphoma, primary medi- astinal B-cell lymphoma, and concurrent or preceding indolent lymphoma were excluded. All participants received standard R-CHOP therapy, then had an inter- im PET scan performed on days 15 through 18 of cycle 3. If the PET scan was negative (defined as a Deauville score 1-3), patients proceeded with 1 additional cycle of R-CHOP; if the PET scan was positive (Deauville score 4-5), patients received involved-field radiation therapy (IFRT) within 5 weeks, followed by ibritumomab tiuxetan. Initially, 159 patients were enrolled, but 1 was up- staged by PET and 26 were considered ineligible due to incorrect histology (n=21), no specimen submitted (n=3), and bulky bone disease (n=2). The 132 remaining evaluable patients (median age = 62 years; range = 18-86) proceeded with 3 cycles of R-CHOP. Of these patients, 62% (n=82) had stage I disease. The median largest diameter on imaging was 3.5 cm (range = 1.0-9.7 cm); 43% of patients (n=57) had extranodal involvement, while 66% (n=87) had involvement only with head and neck. Stage-modified international prognostic index (smIPI) was 0 in 27% of patients, I in 42%, II in 28%, and III in 4% of patients. The study population also included 4 patients (3%) with double-hit lymphoma (DHL), either MYC/BCL2 (n=2) or MYC/BCL6 (n=2). Prior to PET scan, 4 patients went off treatment, leaving 128 patients who underwent PET scans. Upon central review, 110 patients were considered PET-negative and 18 were PET-positive. Dr. Persky noted that, of the PET-positive patients, 4 were due to infection (Deau- ville X) and so were treated as having a PET-negative scan. One patient in the PET-negative arm died, so 113 patients continued R-CHOP per study protocol. In the “truly PET-positive” group, 2 patients refused radiation, and the 12 remaining patients received per-protocol IFRT plus ibritumomab tiuxetan. During a median follow-up of 4.5 years (range = 1.1-7.5), only 5 patients had progressive disease: 3 who received 4 cycles of R-CHOP, 1 who was PET-positive but declined radiation, and 1 who went off treatment after the first cycle of R-CHOP. 30 Focus on Lymphoid & Plasma Cell Malignancies Two study participants died from lymphoma, while 11 patients died from non-lymphoma causes (including 1 PET-negative patient who died from secondary acute myeloid leukemia and another who died of lung adeno- carcinoma that was diagnosed via PET scan). Dr. Persky pointed out that the patients in the latter group were older, with a median age of 80 years. Overall, survival outcomes were similar between PET-negative and PET-positive patients, confirming the authors’ hypothesis that PET-directed therapy would improve survival by guiding intensity of treatment based on risk. The 5-year progression-free survival (PFS; primary endpoint) and OS rates for PET-positive and PET-negative patients, respectively, were: • PFS: 86% vs. 88% • OS: 93% vs. 91% This compared favorably with the historical 5-year PFS for patients with limited-stage DLBCL, which has been reported at 85%, Dr. Persky said. He added that survival outcomes appeared to differ according to disease stage at enrollment. For example, patients with smIPI stage 0 had a 5-year PFS of 97%, stage I and II had a 5-year PFS of 86%, and stage III had a 5-year PFS of 30%. At the time of data presentation, all 4 patients with “dou- ble hit” lymphoma (DHL) had disease that was still in remission. Together with results from the FLYER trial, which suggested that younger patients with favorable-prognosis limited stage disease can achieve similarly high 5 year PFS and OS rates with 4 cycles of R-CHOP plus two cycles of rituximab monotherapy as with 6 cycles of R-CHOP, “this NCTN trial establishes four cycles of R-CHOP alone as the new standard approach to limited-stage disease for the majority of patients,” Dr. Persky said. 2 He noted, however, that because of the small number of lymphoma events, the researchers were unable to draw conclusions about the prognostic ability of scoring systems like smIPI or lymphoma subtype. ● The authors report no relevant conflicts of interest. References 1. Persky D, Li H, Stephens D, et al. PET-directed therapy for patients with limited-stage diffuse large B-cell lymphoma - results of intergroup NCTN Study S1001. Abstract #626. Presented at the 2019 American Society of Hematology Annual Meeting, December 8, 2019; Orlando, FL. 2. Poeschel V, Held G, Ziepert M, et al. Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER): a randomised, phase 3, non-inferiority trial. Lancet. 2020;394:2271-2281.