Dataset Information

Tumor Lysis, Adverse Events, and Dose Adjustments in 297 Venetoclax-Treated CLL Patients in Routine Clinical Practice.

ABSTRACT:

Purpose

Clinical trials of venetoclax reported negligible rates of clinical tumor lysis syndrome (TLS) in patients with chronic lymphocytic leukemia (CLL) when using an extended dose escalation schedule. We aimed to understand TLS prophylaxis, rates of select adverse events (AE), and impact of dosing modifications in routine clinical practice.

Experimental design

This retrospective cohort study included 297 CLL venetoclax-treated patients outside of clinical trials in academic and community centers. Demographics, baseline disease characteristics, venetoclax dosing, TLS risk and prophylaxis, and AEs were collected.

Results

The group was 69% male, 96% had relapsed/refractory CLL, 45% had deletion chromosome 17p, 84% had unmutated IGHV, 80% received venetoclax monotherapy, and median age was 67. TLS risk was categorized as low (40%), intermediate (32%), or high (28%), and 62% had imaging prior to venetoclax initiation. Clinical TLS occurred in 2.7% of patients and laboratory TLS occurred in 5.7%. Pre-venetoclax TLS risk group and creatinine clearance independently predict TLS development in multivariable analysis. Grade 3/4 AEs included neutropenia (39.6%), thrombocytopenia (29.2%), infection (25%), neutropenic fever (7.9%), and diarrhea (6.9%). Twenty-two patients (7.4%) discontinued venetoclax due to an AE. Progression-free survival was similar regardless of number of dose interruptions, length of dose interruption, and stable venetoclax dose.

Conclusions

These data provide insights into current use of venetoclax in clinical practice, including TLS rates observed in clinical practice. We identified opportunities for improved adherence to TLS risk stratification and prophylaxis, which may improve safety.

SUBMITTER: Roeker LE

PROVIDER: S-EPMC8020996 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

Tumor Lysis, Adverse Events, and Dose Adjustments in 297 Venetoclax-Treated CLL Patients in Routine Clinical Practice.

Roeker Lindsey E LE Fox Christopher P CP Eyre Toby A TA Brander Danielle M DM Allan John N JN Schuster Stephen J SJ Nabhan Chadi C Hill Brian T BT Shah Nirav N NN Lansigan Frederick F Yazdy Maryam M Cheson Bruce D BD Lamanna Nicole N Singavi Arun K AK Coombs Catherine C CC Barr Paul M PM Skarbnik Alan P AP Shadman Mazyar M Ujjani Chaitra S CS Tuncer Hande H HH Winter Allison M AM Rhodes Joanna J Dorsey Colleen C Morse Hannah H Kabel Charlene C Pagel John M JM Williams Annalynn M AM Jacobs Ryan R Goy Andre A Muralikrishnan Sivraj S Pearson Laurie L Sitlinger Andrea A Bailey Neil N Schuh Anna A Kirkwood Amy A AA Mato Anthony R AR

Clinical cancer research : an official journal of the American Association for Cancer Research 20190419 14

<h4>Purpose</h4>Clinical trials of venetoclax reported negligible rates of clinical tumor lysis syndrome (TLS) in patients with chronic lymphocytic leukemia (CLL) when using an extended dose escalation schedule. We aimed to understand TLS prophylaxis, rates of select adverse events (AE), and impact of dosing modifications in routine clinical practice.<h4>Experimental design</h4>This retrospective cohort study included 297 CLL venetoclax-treated patients outside of clinical trials in academic and ...[more]

PMID: 31004001

Similar Datasets

Project description:BackgroundIbrutinib, an inhibitor of Bruton's tyrosine kinase, and venetoclax, an inhibitor of B-cell lymphoma 2 protein, have been approved for patients with chronic lymphocytic leukemia (CLL). Preclinical investigations have indicated potential synergistic interaction of their combination.MethodsWe conducted an investigator-initiated phase 2 study of combined ibrutinib and venetoclax involving previously untreated high-risk and older patients with CLL. All patients had at least one of the following features: chromosome 17p deletion, mutated TP53, chromosome 11q deletion, unmutated IGHV, or an age of 65 years or older. Patients received ibrutinib monotherapy (420 mg once daily) for 3 cycles, followed by the addition of venetoclax (weekly dose escalation to 400 mg once daily). Combined therapy was administered for 24 cycles. Response assessments were performed according to International Workshop on Chronic Lymphocytic Leukemia 2008 criteria. Minimal residual disease was assessed by means of multicolor flow cytometry in bone marrow (sensitivity, 10-4).ResultsA total of 80 patients were treated. The median age was 65 years (range, 26 to 83). A total of 30% of the patients were 70 years of age or older. Overall, 92% of the patients had unmutated IGHV, TP53 aberration, or chromosome 11q deletion. With combined treatment, the proportions of patients who had complete remission (with or without normal blood count recovery) and remission with undetectable minimal residual disease increased over time. After 12 cycles of combined treatment, 88% of the patients had complete remission or complete remission with incomplete count recovery, and 61% had remission with undetectable minimal residual disease. Responses were noted in older adults and across all high-risk subgroups. Three patients had laboratory evidence of tumor lysis syndrome. The adverse-event profile was similar to what has been reported with ibrutinib and venetoclax.ConclusionsIn this study, combined venetoclax and ibrutinib was an effective oral regimen for high-risk and older patients with CLL. (Funded by AbbVie and others; ClinicalTrials.gov number, NCT02756897.).

Dataset Information

Tumor Lysis, Adverse Events, and Dose Adjustments in 297 Venetoclax-Treated CLL Patients in Routine Clinical Practice.

Purpose

Experimental design

Results

Conclusions

Publications

Tumor Lysis, Adverse Events, and Dose Adjustments in 297 Venetoclax-Treated CLL Patients in Routine Clinical Practice.

Similar Datasets

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