SUGGESTED TREATMENT REGIMENS...CLL/SLL with del(17p)/TP53 mutation...Preferred regimens...Ibrutinib

Eligible patients were ≥ 18 years, with a confirmed diagnosis of CLL/SLL, and who initiated ibrutinib therapy...in previously untreated patients with del17p and/or TP53 mutation, or in patients with relapsed or refractory disease R/R….Median PFS was 47.5 months (48.5/51.6 months in pro/ret). LOT and age (≤ 75 vs > 75 years) were statistically significant predictive factors for PFS. In patients with 0, 1, 2, and ≥ 3 prior LOT, median PFS was: not estimable (NE), 53.9 months, 47.5 months, and 33.5 months, respectively (Figure). At 48 months’ follow-up, ORR was 91.4%....In this longer follow-up of the real-world FIRE study reflecting clinical practice in France, ibrutinib was shown to be an effective treatment for patients with CLL/SLL, and patients who received ibrutinib in earlier LOT achieved better PFS.

The pooled analysis included 89 patients with TP53 aberrations receiving first-line treatment with single-agent ibrutinib...Among 16 patients with del(17p) who had TP53 sequencing results available, 11 had both del(17p) and TP53 mutations...For the 11 patients who had both del(17p) and TP53 mutations, median PFS was 42·8 months (95% CI: 7·2 months to NE)...In the overall pooled population, the four-year OS rate was 88% (95% CI: 78–93) (Figure 1B). Most patients (83/89) achieved a response, resulting in an ORR of 93% (95% CI: 86–98), including 39% who achieved a CR.

One hundred TN CLL patients were recruited in this study....Seventy-seven patients were IGHV unmutated, 33 displayed only 17p-, 22 only TP53m and 45 both 17p- and TP53m....The overall response rate was 84%, including 10% of complete remissions.

Seventy-seven patients were IGHV unmutated, 33 displayed only 17p-, 22 only TP53m and 45 both 17p- and TP53m….The overall response rate was 84%, including 10% of complete remissions...The 12, 24 and 36-month PFS was 91%, 82% and 75%, respectively….ibrutinib in TN CLL patients with TP53 abnormalities, confirming the efficacy of ibrutinib in this subset of patients.

In the CLL cohort...59.1%, had del17p and/or TP53 mutation, and 72.5% had no IGHV mutation. The median PFS for CLL was 38.3 months (51.5/not reached [NR] months in the pro/ret cohorts). ORR was 90.0% (complete response [CR] 16.7%, partial response [PR] 51.6%...

27 treatment-naive CLL patients with 17p deletion and/or TP53 mutation received ibrutinib, alone (n=15) or in combination with rituximab (n=12)….Our data demonstrate that frontline therapy with ibrutinib results in long-term remissions in high-risk CLL patients with 17p deletion and/or TP53 mutations, despite the lack of deep remissions, with an estimated 5-year PFS of 66%.