Treatment outcomes of Limited Stage Grade 3A Follicular Lymphoma

Abstract

Introduction: While radiotherapy is an established standard of care for limited stage, low grade follicular lymphoma (FL), the management of localized FL grade 3A (FL3A) disease remains controversial. We reviewed the outcomes of grade 3A patients treated with definitive RT, combined modality therapy (CMT), or systemic therapy (ST) alone. Methods: We retrospectively analyzed a single institution database to identify newly-diagnosed, grade FL3A patients with Ann Arbor stage I/II disease treated between 2000 and 2021. Patients were stratified by definitive treatment modality including RT monotherapy, CMT, or ST. Best post-RT imaging response was evaluated using Lugano criteria for all by CT, and by PET if available. Rate of complete response (CR) was compared between the three treatment modalities. Progression-free survival (PFS) and Overall survival (OS) were calculated using Kaplan Meier from first day of treatment. Univariable Cox regression was used to assess possible clinicodemographic associations with PFS. Results: 84 patients (median age 62, 38% male) were analyzed with median follow-up of 6.9 years from initiation of treatment. Patients were stage I (73%) or II (27%) and 92% were initially PET staged at diagnosis. 29 (35%) had extranodal disease. The median (IQR) maximum SUV and size prior to treatment were 9.8 (5.4, 14.0) and 3.2 (2.0, 4.5) cm respectively. RT was the most common treatment modality (n = 48, 57%), followed by CMT (n = 21, 25%), then ST (n = 15, 18%). For RT/CMT patients the planned RT dose was most commonly 36 Gy (32%, range 4–40 Gy). 2 patients (3%) received very low dose of 4 Gy. Of the CMT/ST patients the most common regimen was 3–4 cycles of R-CHOP (53%). 3 patients (8%) received Rituximab alone. Compared to RT patients, ST patients were most likely to have been diagnosed after 2010 (p = 0.002) and have stage II disease (p < 0.001), while CMT patients were more likely to be female (p = 0.03) and have grade 3 disease not further characterized (p = 0.002). The rates of CR post-treatment were 88% for RT, 100% for CMT, and 87% for ST. Factors significantly associated with PFS univariably included the treatment modality (CMT vs. RT HR 0.30, 95% CI: 0.10–0.91, p = 0.03), and presence of low-grade FL component in the biopsy (HR 3.33, 95% CI: 1.43–7.78, p = 0.005). Age, sex, stage, extranodal status, Ki67 score, size, and SUV were not predictive of PFS. The probability of transformation to DLBCL was 4.2% (95% CI: 1.1%–11%) at 5 years after treatment. Overall survival was excellent for all treatment modalities with median OS of 18 years for CMT, and not reached for RT or ST. Keywords: Combination Therapies, Indolent non-Hodgkin lymphoma, Radiation Therapy Conflicts of interests pertinent to the abstract. A. Zelenetz Consultant or advisory role: ADC Therapeutics, AbbVie, Adaptive Biotechnologies Corp Arvinas, Inc. AstraZeneca BeiGene, Ltd. Bristol-Myers Squibb, Curio Science LLC, Dava Oncology, Genentech, Instituto de Ciencias Integradas, Kyowa Kirin Co., Ltd. MEI Pharma, Inc., Medscape, Oncopeptides, AB Sandoz, Inc., Secura Bio, Inc., Suzhou Liang Yihui Network Science and Technology Company, Limited G. Salles Consultant or advisory role: AbbVie, Aptitude Health, Bayer, BeiGene, Ltd., Bio Ascend, Bristol-Myers Squibb, Celgene, Epizyme, Everest Clinical Research Corporation, GenMab, Genentech, Gilead Pharmaceutical, Incyte, Ipsen, Janssen Pharmaceutical, Nordic Nanovector ASA, s, Inc., Loxo Oncology, Miltenyi Biotec Incorporated, MorphoSys AG, Novartis, Owkin, Inc., Physicians' Education Resource, RAPT Therapeutics, Regeneron Pharmaceuticals, Inc., Roche, Scientific Education Support Ltd., Takeda Millennium J. Yahalom Consultant or advisory role: Convergent R.N.R Ltd. B. Imber Consultant or advisory role: GT Medical Technologies, Inc.