Ianalumab plus ibrutinib resulted in high response rates among patients with chronic lymphocytic leukemia (CLL), with some patients able to discontinued ibrutinib after achieving undetectable minimal residual disease (uMRD).
Ianalumab is an anti-BAFF-R monoclonal antibody, Janghee Woo, MD, PhD, of the Novartis Institutes for BioMedical Research, explained at the AACR Annual Meeting 2023. It has a dual mechanism of action that inhibits B-cell differentiation, proliferation, and survival, and depletes B-cells through antibody-dependent cellular cytotoxicity within the tumor microenvironment.
This phase 1b, dose-escalation and expansion trial (ClinicalTrials.gov Identifier: NCT03400176) treated 15 patients with CLL who were already receiving ibrutinib with different doses of Ianalumab for 6 cycles. Patients with evidence of disease continued the combination to cycle 8 and then followed every 3 months for 2 years.
The dose expansion portion of the trial assigned 24 patients into 2 arms: arm A included patients who had received ibrutinib for 1 year or more with residual disease but not clinical relapse and arm B included patients who acquired resistance mutations to ibrutinib but did not demonstrate clinical relapse.
The primary objectives included determining the recommended dose for expansion (RDE) and safety. The secondary objectives included antitumor activity.
The median age of all patients at baseline was 65 and 28.2% were female. The majority of patients had an Eastern Cooperative Oncology Group performance status of 0 and the median number of prior treatment regimens was 1. There were 30.8% of patients with no prior treatment. The median duration of ibrutinib was 2.95 years. There were 15.4% of patients with mutated IGHV, 20.5% with mutated BRKC481, 12.8% with mutated PLCy2, 15.4% with a 17p deletion, 23.1% with an 11q deletion, 25.6% with a 13q deletion, and 7.7% with trisomy 17. A complex karyotype was present among 51.3% of patients.
The ORR at cycle 9 or before treatment discontinuation was 56.7%, with a complete response (CR) rate of 37.8% The CR + CR with incomplete marrow recovery (CRi) was 40.5%.
Patients who were in their first line of treatment demonstrated better outcomes than patients with had relapsed or refractory disease. The ORR for previously-untreated patients was 81.8% with a CR of 54.5% and a CR + CRi of 63.6%, whereas the ORR and CR of patients with relapsed/refractory disease was 46.2% and 30.8%, respectively.
The uMRD in blood or bone marrow was achieved by 45.9% of patients by cycle 9 of treatment, including 63.6% of patients in their first line of therapy and 38.5% of patients with relapsed/refractory disease.
Of the patients who achieved CR or had uMRD, 43.2% elected to discontinue ibrutinib, remaining off therapy for 4.9 to 19.8 months.
There were no dose-limiting toxicities and the RDE was determined to be 3.0 mg/kg given every 2 weeks. There were 33.3% of patients who developed a grade 3 or higher adverse event, with the most common including neutrophil or lymphocyte count decrease, hypophosphatemia, and lipase increase.
“Ianalumab and ibrutinib combination was well-tolerated, appeared highly active, and had an acceptable safety profile,” Dr Woo concluded.
Disclosures: This research was supported by Novartis. Please see the original reference for a full list of disclosures.
Rogers KA, Yan P, Flinn IW, et al. Assessing clinical and pharmacodynamic (PD) profiles of patients (pts) with chronic lymphocytic leukemia (CLL) on ianalumab (VAY736) + ibrutinib. AACR 2023. April 14-19, 2023. Abstract CT021.
This article originally appeared on Hematology Advisor