First-line ibrutinib plus venetoclax for non-blastoid mantle cell lymphoma in patients ≥65 years or with TP53 mutations

The phase 3 SYMPATICO study included an open-label cohort to evaluate the efficacy and safety of first-line ibrutinib plus venetoclax in patients with non-blastoid mantle cell lymphoma (MCL) ≥65 years (n=65), or ≥18 years with a TP53 mutation (TP53m) (n=11). Eligible patients received oral ibrutinib 560 mg once daily and venetoclax (5-week ramp-up to 400 mg once daily) for 2 years, then single-agent ibrutinib 560 mg until disease progression or unacceptable toxicity. In total, 78 patients were enrolled. With median time on study of 40.5 months (range, 0.6+ to 46.9), the complete response (CR) rate was 69% (95% CI, 58-79), and the overall response rate was 95% (95% CI, 87-99). The median duration of response was 37.1 months (95% CI, 30.3-not estimable [NE]). Median progression-free survival (mPFS) was 40.2 months (95% CI, 29.4-NE); median overall survival (OS) was not reached (3-year OS rate, 79% [95% CI, 68-86]). In patients ≥65 years, CR rates were 76% (no TP53m) and 44% (with TP53m), mPFS was 40.2 and 22.0 months, and 3-year OS was 85% and 66%, respectively. In adult patients <65 years (with TP53m), the CR rate was 73%, mPFS was 15.4 months, and 3-year OS was 73%. The most common treatment-emergent adverse events were diarrhea (49%), fatigue (37%), neutropenia (35%), and COVID-19 (32%). First-line ibrutinib plus venetoclax showed promising efficacy, with high CR rates and durable remissions, in patients with previously untreated non-blastoid MCL and may be an option for patients ≥65 years or patients of any age with TP53m. NCT03112174.