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Association details:
| Biomarker: | TP53 mutation |
|---|---|
| Cancer: | Chronic Lymphocytic Leukemia |
| Drug: | Zydelig (idelalisib) (PI3Kδ inhibitor) |
| Direction: | Sensitive |
Evidence:
Source:
Excerpt:
Suggested treatment regimens...CLL/SLL with del(17p)/TP53 mutation…Relapsed/refractory therapy…Other recommended regimens…Idelalisib
Source:
Title:
Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
Excerpt:
...it is recommended that patients with TP53 deletion/mutation are treated with novel inhibitors (ibrutinib; idelalisib and rituximab) in front-line and relapse settings.
DOI:
10.1093/annonc/mdv303
Source:
Title:
Efficacy and Safety of Idelalisib in Combination With Ofatumumab for Previously Treated Chronic Lymphocytic Leukemia
Excerpt:
...Overall Response Rate`Lymph Node Response Rate`Overall Survival`Progression-Free Survival in Subgroup of Participants With Chromosome 17p Deletion and/or TP53 Mutation`Complete Response Rate...
Trial ID:
Source:
Title:
Updated results of a phase III randomized, controlled study of idelalisib in combination with ofatumumab for previously treated chronic lymphocytic leukemia (CLL).
Published date:
05/20/2016
Excerpt:
Pts with CLL progressing ≤ 24 mo from last therapy...With > 8 mos longer follow-up, IDELA + OFA vs OFA continues to show superior PFS and ORR, and now demonstrates superior OS in pts with del17p/TP53mut and a trend of improvement of OS in the ITT population.
DOI:
10.1200/JCO.2016.34.15_suppl.7515
Trial ID:
Source:
Title:
delalisib, an inhibitor of phosphatidylinositol 3-kinase p110d, for relapsed/refractory chronic lymphocytic leukemia
Excerpt:
The ORR for the 13 subjects with del17p and/or TP53 mutation who had a median of 5 prior regimens, and 85% of whom were refractory to their most recent prior regimen, was 54% (7/13), and the median PFS was 3 months. Of this subgroup, 7 subjects were treated at doses of ≥150 mg bid, and their median PFS was 5 months....This study demonstrates the clinical utility of inhibiting the PI3Kδ pathway with idelalisib.
DOI:
10.1182/blood-2013-11-535047
Trial ID:
Source:
Title:
664 Clinical and Biological Impact of TP53 Alterations in Del(11q) Chronic Lymphocytic Leukemia
Published date:
11/04/2020
Excerpt:
We generated isogenic HG3-Cas9 CLL-derived cell lines harboring monoallelic del(11q) (targeting 11q22.1/11q23.3 regions) and further loss-of-function mutations in ATM and/or TP53 to mimic all the possible combinations observed in our CLL cohort...We next assessed whether these cell models could predict responses of these combined abnormalities to BTK and PI3K inhibitors...We observed that HG3-del(11q) TP53MUT and HG3-TP53MUT cells showed partial response to ibrutinib and idelalisib, although the IC50 values were still higher than the ones observed in HG3WT clones, especially with idelalisib (27.4 and 20.6 vs. 1.8 uM, respectively).
