Updated Safety and Efficacy Data for Ibrutinib as First-Line Treatment in Older Patients with CLL or SLL

TOP - February 2017, Vol 10, No 1 - Conference Correspondent

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) occur mainly in older patients, who are likely to have several comorbidities and who often are unable to receive aggressive drug therapies, such as alkylating drugs, which are typically used for patients with CLL or SLL. Ibrutinib is the first FDA-approved once-daily inhibitor of Bruton’s tyrosine kinase indicated for the treatment of patients with CLL/SLL, thereby allowing this patient population to receive treatment without chemotherapy.

The phase 3 RESONATE-2 clinical trial compared the efficacy and safety of ibrutinib and chlorambucil in patients (aged ≥65 years) with treatment-naïve CLL or SLL; at a median of 18.4 months of follow-up, ibrutinib showed significant reduction in the risk for disease progression or death by 84%.

Updated results for the RESONATE-2 study at a follow-up of 29 months were reported by Barr and colleagues for treatment-naïve patients with CLL or SLL. A total of 269 patients (median age, 73 years) with treatment-naïve CLL or SLL were randomized to receive ibrutinib 420 mg daily until disease progression or chlorambucil 0.5 mg/kg (maximum 0.8 mg/kg) on days 1 and 15 of a 28-day cycle, for a total of up to 12 cycles. Patients with deletion (del)17p were excluded from this extension study. Patients who received chlorambucil whose disease progressed were allowed to cross over to the ibrutinib arm. The primary end point was progression-free survival (PFS); the secondary end point was overall survival (OS).

At a median of 29 months of follow-up, the increased duration of PFS was sustained, at 89%, with ibrutinib versus 34% with chlorambucil at 24 months. The PFS improved significantly with ibrutinib versus chlorambucil at all the high-risk subgroups, including those with del11q and those without IGHV mutation. Ibrutinib demonstrated a 99% reduction in the risk for disease progression or death, and a 92% reduction in the subgroup of patients with del11q.

Overall, 41% of patients switched from chlorambucil to ibrutinib; the 2-year OS rates based on the OS analysis in the intent-to-treat population resulted in estimated rates of 95% in the ibrutinib arm and 84% in the chlorambucil arm. Similarly, the investigator-assessed overall response rate was 92% with ibrutinib and 36% with chlorambucil.

Ibrutinib showed higher sustained hematologic improvements from baseline versus chlorambucil in patients with anemia (90% vs 45% improvement in hemoglobin) and thrombocytopenia (80% vs 46% improvement in platelet counts). Grade ≥3 adverse events (AEs) in ≥5% of patients included neutropenia, pneumonia, anemia, and hypertension; AEs of any grade leading to dose reductions were reported in 13% of patients. The incidence of the common grade ≥3 AEs in the ibrutinib-treated patients typically decreased over time. Overall, important AEs decreased in frequency with longer follow-up.

At a median of 29 months, ibrutinib continued to demonstrate significant efficacy, with an 88% reduction in the risk for disease progression or death versus chlorambucil.

Related Items
Palliative Care Use Dismal Among Patients with Hematologic Malignancies
TON - March 2018, Vol 11, No 1 published on March 9, 2018 in Conference Correspondent, ASH, Palliative Care, Hematologic Cancers
Oral Multiple Myeloma Medication Linked to Decreased Productivity Loss
Chase Doyle
TON - March 2018, Vol 11, No 1 published on March 9, 2018 in Conference Correspondent, ASH, Multiple Myeloma
Ivosidenib, New IDH1 Inhibitor, Elicits Complete Response in Relapsed Acute Myeloid Leukemia
Wayne Kuznar
TON - March 2018, Vol 11, No 1 published on March 9, 2018 in Conference Correspondent, Drug Updates & News, ASH
“Superhero” Navigators Convene at the 8th Annual Navigation & Survivorship Conference
Meg Barbor, MPH
TON - March 2018, Vol 11, No 1 published on March 9, 2018 in Conference Correspondent, AONN+
Silent Patients Find Their Voices Through an Advocate’s Journey
Meg Barbor, MPH
TON - March 2018, Vol 11, No 1 published on March 9, 2018 in Patient Advocacy, Conference Correspondent, ESMO
Measuring Financial Well-Being in Cancer Survivorship
Meg Barbor, MPH
TON - March 2018, Vol 11, No 1 published on March 9, 2018 in Conference Correspondent, Survivorship
Combining Immunotherapy and Radiotherapy Shows Good Synergy
Chase Doyle
TON - March 2018, Vol 11, No 1 published on March 9, 2018 in Immunotherapy, Conference Correspondent
Quizartinib Combinations Show High Activity in Newly Diagnosed Acute Myeloid Leukemia with FLT3 Mutation
Wayne Kuznar
TON - March 2018, Vol 11, No 1 published on March 9, 2018 in Conference Correspondent, Drug Updates & News
Humanizing Cancer Care: The Patient Perspective
Gail Thompson
TON - March 2018, Vol 11, No 1 published on March 9, 2018 in Conference Correspondent, ACCC
Emerging Safety Data with Checkpoint Inhibitors
Phoebe Starr
TON - November 2017, Vol 10, No 6 published on November 27, 2017 in Conference Correspondent
Last modified: February 2, 2017