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453 Prognostic Factors Other Than Age Drive the Risk of Disease Progression in Adults with Burkitt Lymphoma Treated with DA-EPOCH-R

Program: Oral and Poster Abstracts
Type: Oral
Session: 627. Aggressive Lymphomas: Clinical and Epidemiological: Clinical Management of Aggressive B cell NHL
Hematology Disease Topics & Pathways:
Clinical Trials, Adults, Epidemiology, Lymphomas, Non-Biological, Clinical Research, B Cell Lymphoma, Chemotherapy, Clinically Relevant, Diseases, Therapies, Lymphoid Malignancies, Study Population, Clinical Practice (e.g. Guidelines, Health Outcomes and Services, and Survivorship, Value; etc.)
Sunday, December 12, 2021: 12:30 PM

Rahul Lakhotia, MBBS1, Kieron Dunleavy, MD2, Jeremy S. Abramson, MD3, Brian K. Link, MD4, Bayard L. Powell, MD5, Christopher Melani, MD1, Andrea Nicole Lucas, RN1*, Seth M. Steinberg, PhD6*, Jonathan W. Friedberg, MD7, Brad S. Kahl, MD8, Richard F. Little, MD, MPH9, Nancy L. Bartlett, MD10, Michelle A. Fanale, MD11, Ariela Noy, MD12, Wyndham H. Wilson, MD, PhD1* and Mark Roschewski, MD13

1Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
2Georgetown University, Washington, DC
3Massachusetts General Hospital Cancer Center, Boston, MA
4Department of Medicine, University of Iowa, Iowa City, IA
5Comprehensive Cancer Center of Wake Forest Baptist Health, Winston-Salem, NC
6Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, MD
7Wilmot Cancer Institute, University of Rochester, Rochester, NY
8Washington University School of Medicine in St. Louis, Saint Louis, MO
9National Cancer Institute, Washington, DC
10Washington University Sch. of Med. Siteman Cancer Center, Saint Louis, MO
11Department of Lymphoma and Myeloma, University of Texas M.D. Anderson Cancer Ctr., Houston, TX
12Memorial Sloan-Kettering Cancer Ctr., New York, NY
13Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD

Introduction

Adults with Burkitt lymphoma (BL) are at risk for both early toxic death and disease progression. Age is associated with a poor prognosis with highly dose-intensive regimens, but it is unclear if this is driven by disease biology or treatment intolerance. We previously reported that survival for adult BL patients treated with DA-EPOCH-R were poorest with CNS, bone marrow (BM) and/or peripheral blood (PB) involvement, but age was not prognostic (Roschewski et al J Clin Oncol 2020). A retrospective study of patients treated with standard regimens outside of clinical trials identified the Burkitt Lymphoma International Prognostic Index (BL-IPI) which stratified patients into risk categories based on 4 variables: age ≥40y, ECOG ≥2, serum LDH >3x ULN, and CNS involvement (Olszewski J Clin Oncol 2021). We analyzed the prognostic utility of BL-IPI to predict time to progression (TTP) and event-free survival (EFS) for adult patients with BL treated on a prospective multicenter study of risk-adapted DA-EPOCH-R.

Methods

NCI 9177 was a multicenter study that included pts ≥ age 18 with any HIV status. Treatment was risk-adapted based on LDH, ECOG status, stage, and largest tumor lesion. Low-risk patients received 3 cycles of DA-EPOCH-RR and high-risk patients received 6 cycles of DA-EPOCH-R with either IT chemo prophylaxis or extended IT treatment for active CNS disease. Event-free survival (EFS) was calculated from study entry until progression, last documentation of active disease, death, or last follow-up. Time to progression (TTP) was calculated from study entry until date of progression. Kaplan-Meier estimation and log-tank tests were used to determine the prognostic utility of the BL-IPI including individual factors. Receiver operating characteristic curves were plotted to determine the c-index which measures the predictive ability of a survival model.

Results

113 patients were enrolled including 31 (27%) low-risk, 55 (49%) intermediate-risk, and 27 (24%) high-risk by BL-IPI. With a median follow up of living patients of 3.3y, the 5-year TTP for pts with high-risk BL-IPI was 78.3% (95% CI: 55-90) compared to 95.2% (95% CI: 88-98)(p=0.022) for pts with low/intermediate IPI (Figure 1A). Pts with high-risk BL-IPI had a lower 5-year EFS of 66.7% (95% CI: 46-81) compared to 94.2% (95% CI: 83-98) for intermediate-risk and 83.6% (95% CI: 65-93) for low-risk, respectively (p=0.004)(Table 1). Pts aged ≥40y had a similar 5-year TTP and EFS of 93.6% (95% CI: 84-98) versus 88.4% (95% CI: 74-95)(p=0.32) and 86.7% (95% CI: 76-93) versus 81.1% (95% CI: 66-90)(p=0.50) compared to pts under 40y. Pts with ECOG PS ≥2 had a worse 5-year TTP and EFS of 76.5% (95% CI: 49-90) versus 94.4% (95% CI: 87-98)(p=0.01) and 61.9% (95% CI: 38-79) versus 89.8% (95% CI: 81-95)(p=0.0004) compared to pts with ECOG PS <2. Pts with serum LDH 3x ULN also had worse 5-year TTP and EFS of 77.3% (95% CI: 54-90) versus 95.2% (95% CI: 88-98)(p=0.008) and 65.4% (95% CI: 44-80) versus 90.4% (95% CI: 82-95)(p=0.001) compared to pts without serum LDH > 3x ULN. Pts with CNS involvement had worse 5-year TTP and EFS of 62.5% (95% CI: 23-86) versus 93.9% (95% CI: 87-97)(p=0.002) and 45.5% (95% CI: 17-71) versus 88.8% (95% CI: 81-94)(p=0.0001) compared to pts without CNS involvement. Nineteen (70%) pts high-risk by BL-IPI had CNS/BM/PB involvement while 8 (30%) had no CNS/BM/PB involvement. Ten (12%) pts with low/intermediate-risk by BL-IPI had CNS/BM/PB involvement and 76 (88%) had no CNS/BM/PB involvement. Pts without involvement of CNS/BM/PB had an excellent prognosis across BL-IPI groups with 5-year TTP of 97.3% (95% CI: 90-99) for low/intermediate-risk by BL-IPI and 100% for high-risk by BL-IPI. Patient with CNS/BM/PB involvement had 5-year TTP of 80.0% (95% CI: 41-95) for low/intermediate-risk by BL-IPI and 66.7% (95% CI: 38-85) for high-risk by BL-IPI (global p=0.006)(Figure 1B). Compared to BL-IPI (C-index 0.62 p=0.13), CNS/BM/PB involvement had better discrimination between prognostic groups (C-index 0.76, p=0.0005).

Conclusion

Patients with low-or intermediate risk BL-IPI scores had an excellent 5-year TTP and EFS of 95% and 94% in NCI 9177. Age is not prognostic with DA-EPOCH-R but CNS/BM/PB involvement is prognostic across BL-IPI groups. Future studies in adults with BL should focus on high-risk disease including younger patients.

Disclosures: Dunleavy: Incyte: Honoraria; Genetech: Honoraria; Pharmacyclics: Honoraria; Bayer: Honoraria; Morphosys: Honoraria; Beigene: Honoraria; Gebmab: Honoraria. Abramson: EMD Serono: Consultancy; Kymera: Consultancy; BeiGene: Consultancy; Bluebird Bio: Consultancy; Genmab: Consultancy; Genentech: Consultancy; Karyopharm: Consultancy; AbbVie: Consultancy; Incyte Corporation: Consultancy; Astra-Zeneca: Consultancy; Allogene Therapeutics: Consultancy; Seagen Inc.: Research Funding; Bristol-Myers Squibb Company: Consultancy, Research Funding; C4 Therapeutics: Consultancy; Morphosys: Consultancy; Kite Pharma: Consultancy; Novartis: Consultancy. Link: MEI: Consultancy; Genentech/Roche: Consultancy, Research Funding; Novartis, Jannsen: Research Funding. Friedberg: Acerta: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Kahl: AbbVie, Adaptive, ADCT, AstraZeneca, Bayer, BeiGene, Bristol-Myers Squibb, Celgene, Genentech, Incyte, Janssen, Karyopharm, Kite, MEI, Pharmacyclics, Roche, TG Therapeutics, and Teva: Consultancy; AbbVie, Acerta, ADCT, AstraZeneca, BeiGene, Genentech: Research Funding. Bartlett: Pharmacyclics: Research Funding; Millennium: Research Funding; Merck: Research Funding; Kite, a Gilead Company: Research Funding; Janssen: Research Funding; Genentech: Research Funding; Forty Seven: Research Funding; Celgene: Research Funding; Bristol Myers Squibb: Research Funding; Autolus: Research Funding; Seagen: Consultancy, Research Funding; Roche/Genentech: Consultancy; ADC Therapeutics: Consultancy, Research Funding. Noy: Epizyme: Consultancy; Rafael Parhma: Research Funding; Morphosys: Consultancy; Targeted Oncology: Consultancy; Medscape: Consultancy; Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy, Honoraria.

*signifies non-member of ASH