Ibrutinib-venetoclax combination shows long-term efficacy in chronic lymphocytic leukemia
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Key takeaways:
- Combination ibrutinib and venetoclax remains effective as first-line CLL treatment.
- Researchers reported 5-year rates of 90% for PFS and 95% for OS.
Combination ibrutinib and venetoclax for first-line treatment yielded a 5-year PFS of 90.1% and 5-year OS of 95.6% in 120 patients with chronic lymphocytic leukemia, according to long-term follow-up data presented at ASH Annual Meeting.
Nitin Jain, MD, from the department of leukemia at The University of Texas MD Anderson Cancer Center, and colleagues reported updated data (median follow-up 61.5 months) on 120 patients with CLL from a phase 2 trial of combined ibrutinib and venetoclax.
Patients with previously untreated CLL and at least one high-risk feature — including del(17p), mutated TP53, del(11q), unmutated IGHV or aged 65 years or older — received ibrutinib (Imbruvica; Janssen, Pharmacyclics) 420 mg daily for 3 cycles followed by addition of venetoclax (Venclexta; AbbVie, Genentech) at a weekly dose-escalation to 400 mg daily. Patients received combined therapy for 24 cycles (28 days/cycle), according to the abstract.
Patients with bone marrow undetectable minimal residual disease (MRD) at 24 cycles of combined therapy discontinued both study drugs, and MRD-positive patients continued ibrutinib. Patients who remained bone marrow MRD positive after cycle 24 were allowed an additional 12 cycles of combination therapy. Researchers examined PFS (defined as the time from the start of study drug to CLL progression, Richter transformation or death from any cause) and assessed blood every 6 months after active therapy.
Of 120 patients, 86% had IGHV-unmutated CLL and 23% had del(17p)/TP53 mutation. The results showed a 5-year PFS of 90.1% and a 5-year OS of 95.6%, as well as a 5-year PFS of 86.1% for patients with del(17p)/TP53 mutation. In total, six patients had CLL progression — one progressed during the first 2 years of therapy and five progressed during the off-therapy phase.
Overall, 52% of patients achieved bone marrow undetectable MRD remission and 36% were bone marrow MRD-positive after 12 cycles of the combination, while 64% achieved bone marrow undetectable MRD remission and 20% were bone marrow MRD-positive after 24 cycles. Further, 72% of patients achieved bone marrow undetectable MRD.
Out of the 77 patients with bone marrow undetectable MRD at the end of cycle 24, 73 discontinued all therapy and four continued ibrutinib, according to the abstract. Of 22 patients who had recurrence of blood MRD during the median follow-up time of 40 months after cycle 24, five had CLL progression, 16 patients had no clinical disease progression and are being monitored without any active therapy for CLL, and onedied of mesothelioma. Of the 55 patients who did not have recurrence of undetectable MRD, 53 remain in long-term follow-up in undetectable MRD remission.
Jain and colleagues also found that 24 patients were bone marrow MRD-positive at the end of cycle 24 of the combination; the one patient who was high-MRD-positive at end of cycle 24 had Richter transformation at that time, while the remaining 23 patients continued monotherapy with ibrutinib. Because of a trial amendment, MRD-positive patients were able to receive 12 additional cycles of venetoclax after cycle 24. Of the 23 patients,18 patients have resumed venetoclax, 11 have achieved undetectable MRD remission during the third year of combined therapy and two patients are still receiving ibrutinib. None of these 23 patients had clinical relapse, according to the results.
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