A “functional cure” may be achievable in a subset of patients with follicular lymphoma treated with chemoimmunotherapy: 15‐year follow‐up of phase iii swog‐s0016

Background: Follicular lymphoma (FL) is considered incurable with current therapies which include chemoimmunotherapy as the standard of care for first line. S0016 enrolled patients with untreated advanced FL (bulky stage II or III–IV) between 2001 and 2008 and randomized them to CHOP × 6 followed by (131) I-tositumomab radioimmunotherapy (CHOP-RIT) or CHOP-R × 6; no maintenance was included. Methods: Fifteen-year PFS and OS were estimated according to the Kaplan–Meier method. Cumulative incidence of disease progression was calculated using the nonparametric Nelson-Aalen estimator with death without progression/relapse treated as a competing risk. Results: Baseline characteristics between the CHOP-RIT (n = 267) and CHOP-R (n = 264) arms were balanced: age (median 53.4 vs. 54.5 years), B symptoms (26% vs. 29%), path grade 3 (9% vs. 8%), high FLIPI risk (26% vs. 22%), high β2M (55% vs. 53%), marrow involvement (55% vs. 56%) and bulky disease (26% vs. 24%). After a median follow-up of 15.5 years, the 15-year OS was 70% (95% CI: 65.9%–74.1%) for the entire cohort, 67% (95% CI: 60.7%, 72.6%) for CHOP-RIT and 73% (95% CI: 67.2%, 78.4%) for the CHOP-R (p-value = 0.56) arm. The 15-year estimate of PFS for the entire cohort was 40% (95% CI: 36.0%, 44.7%). The PFS was superior in the CHOP-RIT arm [47% (95% CI: 40.4%, 53.0%)] versus CHOP-R [34% (95% CI: 28.2%, 40.0%)] (p-value = 0.004). While the overall incidence of progression increased overtime, the average progression rate dramatically decreased: 6.8% (0–5 years), 2.3% (5–10 years), 1.1% (10–15 years) and 0.6% (15%–20%). Cumulative incidence of progression at 15-years for the entire study population was 50.5% (95% CI: 46.5%–54.8%) and was lower in the CHOP-RIT arm vs. CHOP-R arm [42.3% (95% CI: 36.1–48.4%) vs. 58.6% (95% CI: 52.2%–64.4%); p-value = 0.0009] There was no difference between the 2 arms in incidence of 2nd malignancies (19.7% vs. 22.1%; p-value = 0.52) or AML/MDS (5.3% vs. 2.2%; p-value = 0.08). The estimate of 15-year cumulative incidence of deaths due to 2nd malignancies were 7% and 5.4% in CHOP-RIT and CHOP-R arms (p-value = 0.45) but the 15-cumulative incidence of deaths due to AML/MDS was higher in CHOP-RIT arm (4.4% vs. 1.2%; p-value = 0.03). The most common causes of death were lymphoma (15.2%), 2nd malignancies (7.2%) and non-cancer medical issues (6.4%) in the CHOP-RIT arm and lymphoma (11.6%), non-cancer medical issues (8.6%) and 2nd malignancies (5.6%) in CHOP-R arm (p-value 0.27). The cumulative incidence of death without progression at 15-years was 9.1% (95% CI: 6.7%–11.9%). The research was funded by: NIH/NCI/NCTN grants U10CA180888, U10CA180819 Keywords: chemotherapy, combination therapies, indolent non-Hodgkin lymphoma Conflicts of interests pertinent to the abstract M. Shadman Consultant or advisory role: AbbVie, Genentech, AstraZeneca, Pharmacyclics, BeiGene, BMS, MorphoSys/Incyte, Kite, Eli Lilly, Genmab, Mustang Bio, Janssen, Regeneron, ADC therapeutics, Fate Therapeutics and MEI Pharma Research funding: Mustang Bio, BMS, Pharmacyclics, Genentech, AbbVie,TG Therapeutics, BeiGene, AstraZeneca, Genmab, MorphoSys/Incyte, Vincerx. J. P. Leonard Consultant or advisory role: Roche/Genentech Research funding: Roche/Genentech A. K. Gopal Consultant or advisory role: Incyte, Kite, Morphosys/Incyte, ADCT, Acrotech, Merck, Karyopharm, Servier, Beigene, Cellectar, Janssen, SeaGen, Epizyme, I-Mab bio, Gilead, Genentech, Lilly, Caribou, Fresenius-Kabi Research funding: Merck, I-Mab bio, IgM Bio, Takeda, Gilead, Astra-Zeneca, Agios, Janssen, BMS, SeaGen, Teva, Genmab