PMID- 33516721
OWN - NLM
STAT- MEDLINE
DCOM- 20220128
LR  - 20220128
IS  - 2152-2669 (Electronic)
IS  - 2152-2669 (Linking)
VI  - 21
IP  - 5
DP  - 2021 May
TI  - Retrospective Analysis of the Impact of Adverse Event-Triggered Idelalisib 
      Interruption and Dose Reduction on Clinical Outcomes in Patients With 
      Relapsed/Refractory B-Cell Malignancies.
PG  - e432-e448
LID - S2152-2650(20)31037-5 [pii]
LID - 10.1016/j.clml.2020.12.016 [doi]
AB  - BACKGROUND: Idelalisib is a phosphatidylinositol 3-kinase delta inhibitor approved 
      for relapsed/refractory follicular lymphoma, a type of indolent non-Hodgkin 
      lymphoma (iNHL), and chronic lymphocytic leukemia (CLL). Idelalisib-triggered 
      adverse events (AEs) may be managed with treatment interruption and/or dose 
      reduction, potentially extending therapy duration and increasing the likelihood 
      of continued response. PATIENTS AND METHODS: Post hoc analyses were conducted to 
      evaluate clinical outcomes after AE-induced idelalisib interruption for 125 
      patients with iNHL and 283 with CLL. RESULTS: Progression-free survival (PFS) was 
      longer for patients with iNHL who experienced >/= 2 interruptions versus those with 
      0 interruptions who discontinued idelalisib or study because of AEs (hazard ratio 
      0.33; P = .0212). Both PFS and overall survival were longer for patients with CLL 
      with >/= 2 interruptions versus 0 interruptions in those who discontinued therapy 
      because of an AE (hazard ratio PFS 0.50, overall survival 0.41; P < .005). 
      Clinical benefits persisted for patients with CLL who experienced treatment 
      interruption after receiving idelalisib for >/= 6 months. Supplementing 
      interruption with dose reduction did not worsen clinical outcomes. However, time 
      off therapy of >/= 8% may diminish the clinical benefit of treatment interruption. 
      CONCLUSION: Idelalisib interruption and dose reduction were associated with 
      enhanced clinical outcomes for patients with relapsed/refractory iNHL or CLL who 
      experienced an AE, supporting this management strategy when indicated.
CI  - Copyright (c) 2020 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Ma, Shuo
AU  - Ma S
AD  - Northwestern University, Robert H. Lurie Comprehensive Cancer Center, Feinberg 
      School of Medicine, Chicago, IL. Electronic address: shuo-ma@northwestern.edu.
FAU - Chan, Rebecca J
AU  - Chan RJ
AD  - Medical Affairs, Gilead Sciences Inc., Foster City, CA.
FAU - Gu, Lin
AU  - Gu L
AD  - Biostatistics, Gilead Sciences Inc., Foster City, CA.
FAU - Xing, Guan
AU  - Xing G
AD  - Biostatistics, Gilead Sciences Inc., Foster City, CA.
FAU - Rajakumaraswamy, Nishanthan
AU  - Rajakumaraswamy N
AD  - Clinical Research, Gilead Sciences Inc., Foster City, CA.
FAU - Ruzicka, Bianca B
AU  - Ruzicka BB
AD  - Medical Affairs, Gilead Sciences Inc., Foster City, CA.
FAU - Wagner-Johnston, Nina D
AU  - Wagner-Johnston ND
AD  - Oncology-Hematologic Malignancies, Johns Hopkins University, Baltimore, MD.
LA  - eng
SI  - ClinicalTrials.gov/NCT01282424
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201224
PL  - United States
TA  - Clin Lymphoma Myeloma Leuk
JT  - Clinical lymphoma, myeloma & leukemia
JID - 101525386
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Purines)
RN  - 0 (Quinazolinones)
RN  - YG57I8T5M0 (idelalisib)
SB  - IM
MH  - Aged
MH  - Antineoplastic Agents/*adverse effects
MH  - Drug Tapering/*methods
MH  - Female
MH  - Humans
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Progression-Free Survival
MH  - Purines/*adverse effects
MH  - Quinazolinones/*adverse effects
MH  - Retrospective Studies
OTO - NOTNLM
OT  - Alternative dosing regimen
OT  - Chronic lymphocytic leukemia
OT  - Follicular lymphoma
OT  - PI3K inhibitor
OT  - Toxicity management
EDAT- 2021/02/01 06:00
MHDA- 2022/01/29 06:00
CRDT- 2021/01/31 20:26
PHST- 2020/10/07 00:00 [received]
PHST- 2020/12/18 00:00 [revised]
PHST- 2020/12/19 00:00 [accepted]
PHST- 2021/02/01 06:00 [pubmed]
PHST- 2022/01/29 06:00 [medline]
PHST- 2021/01/31 20:26 [entrez]
AID - S2152-2650(20)31037-5 [pii]
AID - 10.1016/j.clml.2020.12.016 [doi]
PST - ppublish
SO  - Clin Lymphoma Myeloma Leuk. 2021 May;21(5):e432-e448. doi: 
      10.1016/j.clml.2020.12.016. Epub 2020 Dec 24.