First-Line Ibrutinib Discontinuation Due to Progression Significantly Higher in CLL With Vs Without Deletion 17p

Patients with treatment-naïve chronic lymphocytic leukemia with the presence of deletion 17p who received treatment with ibrutinib in the first line were more likely to have poor survival and to discontinue treatment due to progression vs those without.

First-line treatment with ibrutinib (Imbruvica) in patients with treatment-naïve chronic lymphocytic leukemia (CLL) and deletion 17p (del[17p]) were more likely to experience poor survival and have a significantly higher rates of treatment discontinuation due to disease progression compared with those without del(17p).

Investigators reported that median overall survival (OS) was significantly worse for patients in the del(17p) cohort at 57.7 months, whereas the median was not reached (NR) in the non-del(17p) cohort (P = .0006). The time to next treatment (TTNT) across both groups was 49.4 months and NR, respectively (P = .033). Additionally, the time to discontinuation (TTD) was 32.5 months in the del(17p) cohort and 42.9 months in the non-del(17p) cohort (P = .337). Those with del(17p) were found to be at a significantly higher risk of death vs those without (HR, 1.70; P = .0031). Although the most common reason for discontinuation was due to toxicity, those with del(17p) were more likely to discontinue due to disease progression (20%) compared with the non-del(17p) group (6%; P <.0001).

“The initial management of patients with CLL/[small lymphocytic leukemia] with del(17p) requires special attention, as they are at higher risk for rapid disease progression,” the investigators wrote. “Combining ibrutinib and venetoclax [Venclexta] in [patients with] del(17p) may address these inferior outcomes, while second-generation BTK may be associated with fewer toxicity-related treatment discontinuations.”

The goals of the study were to describe and compare baseline factors among patients with and without the presence of del(17p) who were treated with ibrutinib monotherapy in the first line. Additionally, investigators sought to determine the real-world OS, TTNT, and TTD, as well as determine reasons for treatment discontinuation.

The analysis included a total of 1069 patients, of whom 23.8% had del(17p). The median age at diagnosis was 70 years and 69 years in both respective groups. Almost all patients received treatment at a community practice (94.6%), with the rest being treated in an academic setting. Investigators noted that those with del(17p) were more likely to have a later Rai stage than those without (P = .0002). First-line ibrutinib was administered sooner following diagnosis in the del(17p) group at a median of 0.8 years vs 2.3 years in the group without del(17p), respectively (P <.0001).

The analysis had a median follow-up of 17.5 months and was longer in the del(17p) group (20.4 months) vs the non-del(17p) group (16.3 months; P =.0001). Most patients had an ECOG performance status of 0 or 1.

In the overall patient cohort, the rate of death was 15.0%, switching to new treatment occurred in 24.2%, and discontinuations accounted for 32.1%. Specifically, the rate of death was 25.2% for those with del(17p) and 11.8% for those without; corresponding rates for starting a new treatment were 33.9% vs 21.2%; and discontinuation was reported in 37.4% and 30.4%, respectively.

Reference

Mato AR, Tang B, Azmi S, et al. A clinical practice comparison of patients with chronic lymphocytic leukemia with and without deletion 17p receiving first-line treatment with ibrutinib. Haematologica. Published online April 21, 2022. doi:10.3324/haematol.2021.280376