Venetoclax plus Ibrutinib in Mantle-Cell Lymphoma: 3-Year Study Update

The AIM trial evaluated the efficacy and safety of ibrutinib combined with venetoclax in patients with relapsed or refractory mantle-cell lymphoma (MCL). The trial is testing the combination of ibrutinib and venetoclax. When data from this study were first analyzed at a median follow-up of 16 months, it was too early to learn about key efficacy measures, including progression-free survival (PFS), duration of response, time to progression, and overall survival (OS). Now, with another 22 months of follow-up, researchers report these data.

A total of 24 patients with MCL were enrolled in the study: 23 had relapsed or refractory disease and 1 had not received any treatment but could not receive chemotherapy. The drug regimen started with ibrutinib alone for 4 weeks, followed by a weekly ramp-up of venetoclax to the full dose. Initially, patients were to continue ibrutinib plus venetoclax until progressive disease or unacceptable toxicity. However, the trial was later changed to allow patients to stop taking both drugs if they achieved a minimal residual disease (MRD)-negative complete response. Patients who elected to stop therapy were closely monitored using MRD testing and regular scans. These patients could start taking both study drugs again if they became MRD positive or experienced clinical progression.

The median age of the 24 patients in the AIM study was 68 years. Most had received 2 previous treatments for MCL and had high-risk disease. Half (50%) had mutations in TP53. The rate of MRD-negativity was 67% by flow cytometry.

As of December 2019, median patient follow-up was almost 38 months. Duration of response is estimated at 74% at 30 months (ie, 75% of patients who have responded will remain in response at 30 months). Time to progression estimate is 60% at 30 months (ie, 60% of patients will remain in remission at 30 months). The median PFS was 29 months and median OS was 32 months.

Among 12 patients with MCL and a TP53 mutation, the complete response rate associated with ibrutinib and venetoclax was 50%. Duration of response in 6 responders ranged from 12+ to 38+ months from study initiation. In contrast, in 10 patients with mutated ATM, the complete response rate was 90%. Among the 9 responders with ATM-mutated MCL, duration of response ranged from 9+ to 38+ months from study initiation.

Of the 13 patients who died on study, 8 had progressive MCL. Among the other 5 deaths, 2 were due to infection, and 1 each to cardiac failure, brain tumor, and graft-versus-host disease.

Five patients who achieved an MRD-negative complete response stopped treatment after a median of 19 months of therapy. One patient progressed after 7 months. The other patients remain progression-free after 6+ to 18+ months off therapy.

Researchers concluded that stopping treatment with ibrutinib and venetoclax is feasible for patients with relapsed or refractory MCL who are in MRD-negative complete remission.

Abstract 756. ASH 2019.

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