DURHAM, NC—The sheer size of the VA enables its researchers to undertake analyses that no other healthcare system in the United States could perform. In the case of chronic lymphocytic leukemia (CLL) with prolymphocytic progression, a newly defined and very rare type of cancer, the scale of the VA and the number of patients it treats with leukemia allowed VA researchers to describe the characteristics and progression of the disease and begin to understand how it responds to current therapies.
CLL with prolymphocytic progression (CLL wPP) is classified in the 5th edition World Health Organization as a CD5+ nonmantle B-cell neoplasm with at least 15% prolymphocytes in the peripheral blood or bone marrow.
Because it so seldom occurs, little is known about CLL wPP, its genetic features, or how it might respond to recently developed targeted therapies for CLL. Researchers at the Durham VA Health Care System in Durham, NC, tapped the VA Corporate Data Warehouse to shed light on the disease. They presented their results at the 64th American Society of Hematology Annual Meeting in New Orleans on Dec. 10.1
Of 36,973 veterans diagnosed with CLL between 2014 and 2022, they identified 93 patients treated at 28 VA facilities who had CD5+ CLL with at least 15% prolymphocytes in the blood or bone marrow. The median follow-up since the date of prolymphocytic progression was 28.1 months and ranged between two weeks and 121.6 months.
The two-year survival rate from the date of progression was 66.2%, and the five-year survival was 35.3%. Of the 93 patients, eight had 55% prolymphocytes and would have been characteristics that would have been classified as having B-cell prolymphocytic leukemia (B-PLL) before CLL wPP was defined as a separate disease. The median time from diagnosis of CLL to having at least 15% prolymphocytes was 3.7 years and for having at least 55% prolymphocytes was 3.2 years. Notably, the team did not find a relationship between overall survival and the percentage of prolymphocytes.
TP53 deletions were more common in patients with at least 55% prolymphocytes (67%) compared to those with 15% to 54% prolymphocytes (39%), with a trend toward a significant impact on overall survival. (2-year OS 55.7% vs. 77.3%, p = 0.050).
More than half of the patients received a BTK, BCL-2 or P13K inhibitor after progression was diagnosed, with ibrutinib being the most common (29 patients) followed by venetoclax (19) and acalabrutinib (8). Nine patients received an anti-CD20 monoclonal antibody plus venetoclax. Most patients had received one previous therapy.
Common symptoms included splenomegaly (62%), constitutional symptoms (32%), and lymphadenopathy (24%). Nearly one-third had hemoglobin of less than 11 g/dL, and 2 in 5 had a platelet count of less than 100 x 109/L. Sixty percent had elevated LDH.
Partial response to therapy occurred in 28% of patients based on iwCLL criteria with a further 38% demonstrating hematologic response but did not have imaging available to document improvement in splenomegaly or lymphadenopathy. Patients who received targeted therapy had a median progression-free survival of 31.4 months. Patients had a median duration of targeted therapy of 13.1 months, with discontinuation primarily for progression or toxicity. One-quarter of patients went on to receive a further line of therapy and one received an allogeneic stem cell transplantation. Twenty-two patients died, with the disease progression being the leading cause (11) followed by infection (3) and unknown causes (5).
The team concluded that TP53 may hold prognostic value, while the percentage of prolymphocytes did not, and oral agents appeared to be effective in these patients.
- Lin C, Scobie MR, Friedman DR, Kelley MJ, Rodgers TD. Prolymphocytic Progression of Chronic Lymphocytic Leukemia in the Era of Novel Targeted Therapies: A Nationwide Veterans Affairs Retrospective Review. Abstract 1816. 2022 ASH Annual Meeting. Dec. 10, 2022.
