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3770 A Multicenter Study Analyzing Survival and Prognostic Factors in Patients with Leukemic Phase Follicular Lymphoma

Program: Oral and Poster Abstracts
Session: 905. Outcomes Research—Lymphoid Malignancies: Poster II
Hematology Disease Topics & Pathways:
Research, Lymphomas, non-Hodgkin lymphoma, Clinical Research, health outcomes research, B Cell lymphoma, Diseases, indolent lymphoma, real-world evidence, Lymphoid Malignancies
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Asaad Trabolsi, MD1, Narendranath Epperla, MD, MS2, Kaitlin Annunzio, DO3, Dan Morgenstern Kaplan, MD, MSc4*, Peter Doukas, MD5*, Frederique St-Pierre, MD6, Brittany McCall, MD7*, Lindsey Fitzgerald, MD8, Sunwoo Han, PhD9*, Isildinha M. Reis, PhD10*, Jennifer Rose Chapman-Fredricks, MD11*, Khaled Alhamad, MD12*, Thomas Ollila, MD13, Reem Karmali, MD, MSc14, Izidore S. Lossos, MD15 and Juan Pablo Alderuccio, MD16

1Sylvester Comprehensive Cancer Center, University of Miami/ Jackson Memorial Hospital, Miami, FL
2Division of Hematology and Oncology, Medical College of Wisconsin, Columbus, OH
3Ohio State University Medical Center, Columbis, OH
4Internal Medicine Residency program, division of internal medicine, Department of Medicine, University of Miami/ Jackson Memorial Hospital, Miami
5Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL
6Department of Medicine, Division of Hematology/Oncology and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Northwestern University Feinberg School of Medicine, Chicago, IL
7Brown Medical School, Providence, RI
8Huntsman Cancer Institute, University of Utah, Salt Lake City, UT
9Biostatistics and Bioinformatics Shared Resource, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL
10Department of Public Health Sciences and Biostatistics and Bioinformatics Shared Resource, University of Miami Miller School of Medicine, Miami, FL
11Department of Pathology, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL
12University of Utah, Salt Lake City, UT
13Brown University, Providence, RI
14Northwestern University, Chicago, IL
15Sylvester Comprehensive Cancer Center, Division of Hematology, University of Miami School of Medicine, Miami, FL
16Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL


Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma. Leukemic-phase FL (LP-FL) is a rare entity comprising 1-3% of FL patients (pts). Controversy exists about prognosis of LP-FL with some studies suggesting worse outcome. No clear cut-point of circulating cells has been used to define LP-FL; however, a level > 5x103^3 cells/uL is defined in GELF criteria for high burden disease. No unified treatment recommendation is present for these pts with some opting to treat as indolent FL and some choosing a more aggressive approach. Furthermore, limited case series (n=7 to 37) on LP-FL are available, hence we aimed to better understand prognosis and treatment strategies associated with better outcome in LP-FL.


Pts with a pathology proven diagnosis of FL in lymph node and/or bone marrow and a positive flow cytometry in peripheral blood for clonal B cells (CBs), at diagnosis or at relapse, were included in the study. Data was collected from 5 academic institution in the US. We report time-to-event outcomes including median progression-free survival (mPFS) and overall survival (mOS) estimated by Kaplan-Meier method (only pts who received therapy included) . Uni and multivariable analyses were performed using Cox regression. CBs were divided into 4 groups: (<1, 1-4.99, 5-9.99, >10) 10^3/uL. Pts treatment was grouped in 4 categories: anti-CD20 monoclonal antibody (CD20mAb), CD20mAb+Bendamustine, CD20mAb+ CHOP, and other. Pts with CD10 negative clones on flow cytometry were excluded as they might represent different lymphoma type.


Sixty-one pts (period 1998 to 2022) were identified in participating institutions with LP-FL, 10 of which had CD10- flow cytometry and excluded from study. Of 51 remaining pts, median age was 56 years (y). Nine (17.6%) pts were Hispanic and 44 (86.2%) pts were white. Most pts (37%) presented asymptomatic lymphadenopathy, 22% with B symptoms, 14% with incidental elevated WBC, 12% with organ compromise and 12% due to other reasons. Overall, B symptoms were present in 20 (39%) pts. Hepato/splenomegaly was present in 22 (43%) pts, high tumor burden (GELF criteria) in 12 (23%) pts, and most pts (n=42; 82%) presented ECOG PS 0-1. We less frequently observed anemia (Hg <12g/dL, n= 10; 20%) and elevated LDH (n=17; 33%). High risk FLIPI score (≥3) was present in 28 (55%) pts. Median count of CBs of 1.62 x 10^3/uL. CBs were <5 10^3/uL in 35 (69%) pts, CBs=5-10 10^3/uL in 6 (12%) pts and CBs >10 10^3/uL in 10 (20%) pts. Median absolute lymphocyte count was 3.0 x10^3/uL. Cytogenetic data was available in tissue biopsies in 13 (25%) pts and all carried t(14;18). Treatment was as follows: 24 (47%) pts with bendamustine + CD20mAb , 15 (29%) pts with CD20mAb + CHOP, 7 (14%) pts were treated with CD20mAb, 3 (6%) pts underwent active surveillance, and 2 (4%) with other treatments. Overall response rate (ORR) was 87%. Of those 31 (65%) pts had complete response (CR) and 11 (23%) pts had partial response (PR).

With a median follow up of 5.5 y the mPFS was 3.6 y and mOS was 9.6 y (Figure 1). Relapse/ progression of disease occurred in 26 (54%) pts and CBc was detect in 12/13 pts in which flow cytometry was done. Transformation on relapse occurred in 7 pts. In pts experiencing disease relapse/progression, CAR T-cell was given to 6 pts with an ORR of 83.3% (CR: in 4 and PR in 1 pts); one pt died due to CAR-T grade 5 neurotoxicity. Death occurred in 13 pts with 6 (46% of all deaths) being lymphoma-related.

Age≥60 and male sex were associated with worse PFS in univariable analysis (Table 1), with age only remaining significant in a multivariable analysis that also included sex and frontline therapy (HR 3.19, p=0.01 ). Notably, FLIPI score, CBs count category, and type of frontline therapy did not predict PFS. Progression of disease within 24 months (POD24) predicted OS in univariable analysis (HR= 3.93; p=0.029). Multivariable analysis for OS was not performed due to small number of deaths.


To our knowledge, this is the largest study of LP-FL. Median OS was around 10 years, a comparable outcome to historical nodal FL survival. Treatment type also did not predict PFS or OS. Circulating monoclonal cell levels did not impact survival . This is notable as the current GELF criteria includes circulating malignant cells ≥5 x10^3/uL as an indication for treatment while our date shows that no set cut-point may be needed. In addition, CAR T-cell appears to be an effective therapy with similar results as in nodal FL.

Disclosures: Trabolsi: Johnson & Johnson: Current equity holder in publicly-traded company. Epperla: Lilly: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Beigene: Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Speakers Bureau. Ollila: ADC Therapeutics: Honoraria; Ono Pharmaceuticals: Honoraria, Research Funding. Karmali: Takeda: Research Funding; BeiGene: Consultancy, Honoraria, Research Funding, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Research Funding; Kite/Gilead: Consultancy, Honoraria, Research Funding; Miltenyi: Consultancy, Honoraria, Research Funding; Calithera: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech/Roche: Consultancy, Honoraria; Lilly: Consultancy, Honoraria; Morphosys: Consultancy, Speakers Bureau; Janssen: Consultancy. Lossos: Adaptive: Honoraria; LRF: Membership on an entity's Board of Directors or advisory committees; NCI: Research Funding; University of Miami: Current Employment; NCI: Research Funding; BeiGene: Consultancy. Alderuccio: Genmab: Research Funding; Abbvie: Consultancy; Genentech: Consultancy; ADC Therapeutics: Consultancy, Research Funding; BeiGene: Research Funding; Regeneron: Consultancy.

*signifies non-member of ASH