Chicago, Illinois—Acalabrutinib in combination with obinutuzumab was well-tolerated and yielded high response rates in patients with treatment-naïve and relapsed/refractory (RR) chronic lymphocytic leukemia (CLL), according to 3-year follow-up results from a phase 1b/2 trial presented at the 2019 ASCO Annual Meeting.

The trial enrolled patients with CLL who were treatment-naïve or RR to 1 or more prior therapies. Acalabrutinib was originally administered at 200 mg daily in the first 15 patients, but after results from the phase 1 study was switched to 100 mg twice daily going forward until disease progression. Obinutuzumab was administered for 6 cycles starting with cycle 2.

The primary end points of the trial were overall response rate and safety. Key secondary endpoints included duration of response, progression-free survival (PFS), overall survival (OS), and minimal residual disease (MRD) status.

A total of 45 patients were included in the trial; 19 treatment-naïve patients and 26 RR patients. At a follow-up of 3 years, 78% of patients remain on therapy and in remission. Therapy was discontinued for 2 patients in the treatment-naïve group and 8 patients in the RR group.

The overall response rate was 95% in the treatment-naïve group and 92% in the RR group and responses have deepened over time. Complete response (CR) was achieved in 31.6% of patients in the treatment-naïve group and 7.7% in the RR group.

The median PFS was not reached in either group. The 39-month PFS was 94.4% in the treatment-naïve group and 42-month PFS was 72.7%.

MRD was assessed in the bone marrow at 12 cycles of therapy and in the blood every 3 cycles using flow cytometry. At 12 cycles, 26% of treatment-naïve patients and 15% of RR patients were MRD-negative in the marrow.

The most common adverse events were upper respiratory tract infection (71%), increased weight (71%), maculopapular rash (67%), cough (64%), diarrhea (62%), headache (56%), nausea (53%), arthralgia (51%) and dizziness (47%).

The most common grade 3/4 adverse events were decreased neutrophil count (24%), syncope (11%), decreased platelet count, increased weight (9%) and cellulitis (9%).

“In conclusion, treatment with acalabrutinib plus obinutuzumab yielded high response rates that have been durable irrespective of high-risk disease status. The combination has been well-tolerated, and most patients remain on treatment and in remission at 3.5 years,” Jennifer Ann Woyach, MD, The Ohio State University Comprehensive Cancer Center, Columbus, lead investigator of the study, told attendees.—Janelle Bradley

Woyach JA, Rogers KA, Bhat SA, et al. Acalabrutinib with obinutuzumab (Ob) in treatment-naive (TN) and relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL): Three-year follow-up. Presented at: the 2019 ASCO Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract 7500.