1225 - Real-world evidence on venetoclax in chronic lymphocytic leukemia: The KROHEM (Croatian cooperative group for hematological diseases) experience

Real-world evidence on venetoclax in chronic lymphocytic leukemia: The KROHEM (Croatian cooperative group for hematological diseases) experience

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the western adult population. The B cell lymphoma-2 (BCL-2) family proteins play a key role in regulating intrinsic apoptosis and in many cancers have a major impact on tumor survival and therapy resistance. Hence, the role of BCL-2 inhibitors is very beneficial in the treatment of CLL. Venetoclax is the first selective, orally bioavailable BCL-2 inhibitor in use for both frontline and relapse/refractory CLL.
In this trial we conducted a multicenter retrospective chart analysis of patients with chronic lymphocytic leukemia treated with venetoclax to describe outcomes and toxicities.
From 2017 to 2023 a total of 188 patients were treated. Median age at venetoclax initiation was 66 years (range 33-90), median prior lines of therapies was 2 (1-6), 42 pts (22%) had del(17p). 64(34%) was treated frontline, 60(32%) received venetoclax as a second line and 64(34%) in later lines. Prior to venetoclax initiation, 33(17%) received a BTK inhibitor and 83(44%) received anti CD20 monoclonal antibody. 75 patients (40%) received venetoclax as a monotherapy while 113(60%) received venetoclax in combination either with rituximab or obinutuzumab.
Overall response rate(ORR) was 85% in all analyzed cohorts with 94 (50%) patients achieved complete remission. 14 (7%) patients were not yet evaluated, 6 (3%) did not respond to treatment and died early in treatment and 6 (3%) patients progressed during treatment. Patients treated in first line had an overall response rate of 100% and in those patients that received venetoclax as a second line had an ORR of 96%. Almost all non responders that died early in treatment or those with early progression were patients treated in third or subsequent lines of therapy.
After a median follow up of 12 months estimated median overall survival (OS) was not reached, 2-year OS for the whole cohort was 83.5%. Figure1. Event free survival (EFS) was 83%. When we analyzed the patients by the treatment lines, in first line EFS was 93.8%, in second line 85% and third and subsequent lines it was 70.3% with a statistically significant difference (p=0.042). Figure 2.
Adverse event of any grade occurred in 50% of the patients during venetoclax therapy. The most frequent adverse events where hematological and non hematological adverse events events include: infections including COVID 19 , tumor lysis syndrome, diarrhea, and elevated liver enzymes. Grade III/IV adverse events occurred in 86(45%) patients, mostly neutropenia (90%), but only 33(18%) needed hospitalization because of febrile neutropenia. 67(35%) had a temporary treatment discontinuation due to adverse events and 53(28%) patients had a dose reduction. In only 11(6%) patients venetoclax treatment was permanently discontinued due to toxicity. Richters transformation occurred in 18(10%) patients. Of those patients 16 were in second or subsequent lines while patients had a concurrent Richters transformation at the beginning of treatment. Two patients developed secondary malignancy(breast cancer and skin cancer).
Our real-life data tend to confirm that venetoclax used as monotherapy or in combination with rituximab or Obinutuzumab is effective treatment for both untreated and relapse/refractory CLL patients. Our data are very similar to the clinical trials data although our follow up is shorter. Adverse events were observed at a similar incidence as in the clinical trials, and the most of adverse events were easily manageable.