The rate of undetectable minimal residual disease (MRD) in the bone marrow increased with the duration of ibrutinib plus venetoclax combination therapy in a study of patients with high-risk, previously untreated chronic lymphocytic leukemia/small cell leukemia (CLL/SLL). These findings were presented at the 61st American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, Florida.
High rates of complete remission were previously reported for adult patients with treatment-naive CLL/SLL enrolled in a single-arm, phase 2 clinical trial (ClinicalTrials.gov Identifier: NCT02756897) evaluating the efficacy and safety combination therapy with a Bruton tyrosine kinase inhibitor, ibrutinib, plus a BCL2 inhibitor, venetoclax, in those with high-risk disease and/or of older age.2 One of the aims of the analysis presented here, which used updated data from that study, was to more closely investigate clinical findings with respect to the presence of MRD in the bone marrow.
Of the 80 patients enrolled in the clinical trial, the median patient age was 65 years, and high-risk disease — which was defined as unmutated IGHV, a TP53 aberration, or a chromosome 11q deletion — in this population was found to be 92%. In patients 70 years or older, mutations were seen was in 30% of the group. Ibrutinib monotherapy was administered for 3 monthly cycles, followed by the addition of venetoclax at cycle 4, and the combination was continued for 24 monthly cycles.
At a median follow-up of 27 months, rates of undetectable MRD in the bone marrow for the 75 patients initiating venetoclax were 0% at 3 months (prior to the addition of venetoclax), 16%, 42%, 65%, and 75% following 3-, 6-, 12-, and 24-monthly cycles of combination therapy, respectively.
Grade 3/4 neutropenia occurred in 51% of patients, whereas only 2% of patients experienced grade 3 thrombocytopenia.
Of the 14 patients who were taken off the study early, the rationales were diverse. Five patients discontinued treatment during the ibrutinib monotherapy phase and 9 stopped combination therapy. Dose reductions for ibrutinib were required in 52% of patients, with atrial fibrillation as the cause in 10% of these individuals. Venetoclax dose reductions were needed in 29% of patients (most commonly for neutropenia).
No progression of CLL was observed for any patients enrolled in the study, although Richter transformation to diffuse large B-cell lymphoma (DLBCL) was observed in 2 patients.
Of the 3 patient deaths, 2 were attributed to fungal infections, although in 1 case the patient may have had symptoms of the infection prior to study enrollment. In the second case, the patient developed fungal pneumonia while receiving ibrutinib monotherapy; the individual was removed from the study after receiving 2 weeks of study drug, but continued to receive ibrutinib off study and died 2 years later. The third case involved a patient with a diagnosis of bilateral pneumonia.
Nitin Jain, MD, from The University of Texas MD Anderson Cancer Center, Houston, Texas,, who was the presenter of the study findings, summarized the results of the study by saying that “combination ibrutinib plus venetoclax is an effective, chemotherapy-free, oral regimen for patients with high-risk, untreated CLL,” and that “responses continue to improve with ongoing therapy.”
- Jain N, Keating MJ, Thompson PA, et al. Combined ibrutinib and venetoclax for first-line treatment for patients with chronic lymphocytic leukemia (CLL). Presented at: 61st American Society of Hematology (ASH) Annual Meeting and Exposition; December 7-10, 2019: Orlando, Florida. Abstract 34.
- Jain N, Keating MJ, Thompson PA, et al. Ibrutinib and venetoclax for first-line treatment of CLL. N Engl J Med. 2019;380:2095-2103.
This article originally appeared on Cancer Therapy Advisor