Difference between revisions of "Idelalisib (Zydelig)"
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==General information== | ==General information== | ||
| − | Class/mechanism: Isoform-selective PI3K (phosphatidylinositol 3-kinase) inhibitor. | + | Class/mechanism: Isoform-selective PI3K (phosphatidylinositol 3-kinase) inhibitor. Idelalisib inhibits class I isoform p110 delta (p110δ), which is one of the mediators of activation of the PI3K pathway and is expressed at high levels by hematopoietic cells, particularly leukocytes. Inhibition of the PI3Kδ kinase pathway affects B-cell receptor (BCR), CXCR4, and CXCR5 signaling, disrupting trafficking and homing of B-cells to the lymph nodes and bone marrow. Lymphoma cells treated with idelalisib have been observed to have impaired chemotaxis, adhesion properties, and cell viability.<ref name=insert>[http://www.gilead.com/~/media/Files/pdfs/medicines/oncology/zydelig/zydelig_pi.pdf Idelalisib (Zydelig) package insert]</ref><ref>[[:File:Idelalisib.pdf | Idelalisib (Zydelig) package insert (locally hosted backup)]]</ref><ref>[http://zydelig.com/ Zydelig manufacturer's website]</ref><ref>S. E. Coutre, J. C. Byrd, R. R. Furman, J. R. Brown, D. M. Benson, N. D. Wagner-Johnston, I. W. Flinn, B. S. Kahl, S. E. F. Spurgeon, B. J. Lannutti, H. K. W. Hsu, R. Ulrich, S. Peterman, L. Holes, L. L. Miller, A. S. Yu. [http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=102&abstractID=83782 Phase I study of CAL-101, an isoform-selective inhibitor of phosphatidylinositol 3-kinase P110d, in patients with previously treated chronic lymphocytic leukemia.] 2011 ASCO Annual Meeting abstract 6631.</ref><ref>I. W. Flinn, J. C. Byrd, R. R. Furman, J. R. Brown, T. S. Lin, C. Bello, N. A. Giese, A. S. Yu. [http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=65&abstractID=34213 Preliminary evidence of clinical activity in a phase I study of CAL-101, a selective inhibitor of the p1108 isoform of phosphatidylinositol 3-kinase (P13K), in patients with select hematologic malignancies.] 2009 ASCO Annual Meeting abstract 3543.</ref><ref>Lannutti BJ, Meadows SA, Herman SE, Kashishian A, Steiner B, Johnson AJ, Byrd JC, Tyner JW, Loriaux MM, Deininger M, Druker BJ, Puri KD, Ulrich RG, Giese NA. [http://www.bloodjournal.org/content/117/2/591.full CAL-101, a p110delta selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability.] Blood. 2011 Jan 13;117(2):591-4. Epub 2010 Oct 19. [https://pubmed.ncbi.nlm.nih.gov/20959606/ PubMed]</ref> |
<br>Route: PO | <br>Route: PO | ||
<br>Extravasation: n/a | <br>Extravasation: n/a | ||
For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as [http://www.thomsonhc.com/home/dispatch Micromedex], [http://online.lexi.com/ Lexicomp], [http://www.utdol.com/online/content/search.do UpToDate (courtesy of Lexicomp)], or the prescribing information.<ref name="insert"></ref> | For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as [http://www.thomsonhc.com/home/dispatch Micromedex], [http://online.lexi.com/ Lexicomp], [http://www.utdol.com/online/content/search.do UpToDate (courtesy of Lexicomp)], or the prescribing information.<ref name="insert"></ref> | ||
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==Diseases for which it is established ''(work in progress)''== | ==Diseases for which it is established ''(work in progress)''== | ||
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*2014-07-23: [http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm406387.htm FDA approved] for the treatment of patients with relapsed [[Chronic lymphocytic leukemia | chronic lymphocytic leukemia (CLL)]], in combination with [[Rituximab (Rituxan) | rituximab]], in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities. ''(Based on GS-US-312-0116)'' | *2014-07-23: [http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm406387.htm FDA approved] for the treatment of patients with relapsed [[Chronic lymphocytic leukemia | chronic lymphocytic leukemia (CLL)]], in combination with [[Rituximab (Rituxan) | rituximab]], in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities. ''(Based on GS-US-312-0116)'' | ||
*2014-07-23: [http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm406387.htm Accelerated approval] for the treatment of patients with relapsed [[Chronic lymphocytic leukemia | small lymphocytic lymphoma (SLL)]] in patients who have received at least two prior systemic therapies. ''(Based on DELTA)'' | *2014-07-23: [http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm406387.htm Accelerated approval] for the treatment of patients with relapsed [[Chronic lymphocytic leukemia | small lymphocytic lymphoma (SLL)]] in patients who have received at least two prior systemic therapies. ''(Based on DELTA)'' | ||
| − | **2022-01-14: | + | **2022-01-14: Accelerated approval for the treatment of patients with relapsed [[Chronic lymphocytic leukemia | small lymphocytic lymphoma (SLL)]] in patients who have received at least two prior systemic therapies voluntarily withdrawn by the manufacturer. ''(No supporting studies are cited)'' |
===[[Follicular lymphoma]] - '''WITHDRAWN'''=== | ===[[Follicular lymphoma]] - '''WITHDRAWN'''=== | ||
*2014-07-23: [http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm406387.htm Accelerated approval] for the treatment of patients with relapsed [[Follicular lymphoma | follicular B-cell non-Hodgkin lymphoma (FL)]] in patients who have received at least two prior systemic therapies. ''(Based on DELTA)'' | *2014-07-23: [http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm406387.htm Accelerated approval] for the treatment of patients with relapsed [[Follicular lymphoma | follicular B-cell non-Hodgkin lymphoma (FL)]] in patients who have received at least two prior systemic therapies. ''(Based on DELTA)'' | ||
| − | **2022-01-14: | + | **2022-01-14: Accelerated approval for the treatment of patients with relapsed [[Follicular lymphoma | follicular B-cell non-Hodgkin lymphoma (FL)]] in patients who have received at least two prior systemic therapies voluntarily withdrawn by the manufacturer. ''(No supporting studies are cited)'' |
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==History of changes in EMA indication== | ==History of changes in EMA indication== | ||
*2014-09-18: Initial authorization | *2014-09-18: Initial authorization | ||
| − | *Zydelig is indicated in combination with an | + | *Zydelig is indicated in combination with an anti-CD20 monoclonal antibody (rituximab or ofatumumab) for the treatment of adult patients with chronic lymphocytic leukaemia (CLL) who have received at least one prior therapy. |
| − | *Zydelig is indicated in combination with an | + | *Zydelig is indicated in combination with an anti-CD20 monoclonal antibody (rituximab or ofatumumab) for the treatment of adult patients with chronic lymphocytic leukaemia (CLL) as first line treatment in the presence of 17p deletion or TP53 mutation in patients who are not eligible for any other therapies. |
*Zydelig is indicated as monotherapy for the treatment of adult patients with follicular lymphoma (FL) that is refractory to two prior lines of treatment. | *Zydelig is indicated as monotherapy for the treatment of adult patients with follicular lymphoma (FL) that is refractory to two prior lines of treatment. | ||
==History of changes in Health Canada indication== | ==History of changes in Health Canada indication== | ||
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*2020-04-21: Conditions were met | *2020-04-21: Conditions were met | ||
==Also known as== | ==Also known as== | ||
| − | *'''Code names:''' CAL-101 | + | *'''Code names:''' CAL-101, GS-1101 |
*'''Brand name:''' Zydelig | *'''Brand name:''' Zydelig | ||
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[[Category:Follicular lymphoma medications (historic)]] | [[Category:Follicular lymphoma medications (historic)]] | ||
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[[Category:EMA approved in 2014]] | [[Category:EMA approved in 2014]] | ||
[[Category:FDA approved in 2014]] | [[Category:FDA approved in 2014]] | ||
[[Category:Health Canada approved in 2015]] | [[Category:Health Canada approved in 2015]] | ||
Latest revision as of 11:23, 9 April 2024
General information
Class/mechanism: Isoform-selective PI3K (phosphatidylinositol 3-kinase) inhibitor. Idelalisib inhibits class I isoform p110 delta (p110δ), which is one of the mediators of activation of the PI3K pathway and is expressed at high levels by hematopoietic cells, particularly leukocytes. Inhibition of the PI3Kδ kinase pathway affects B-cell receptor (BCR), CXCR4, and CXCR5 signaling, disrupting trafficking and homing of B-cells to the lymph nodes and bone marrow. Lymphoma cells treated with idelalisib have been observed to have impaired chemotaxis, adhesion properties, and cell viability.[1][2][3][4][5][6]
Route: PO
Extravasation: n/a
For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.[1]
Diseases for which it is established (work in progress)
Diseases for which it is used
Diseases for which it was used
Patient drug information
- Patient counseling information may be found in the Idelalisib (Zydelig) package insert[1]
Suggestions for SAE monitoring/prevention
- Administer PCP/PJP prophylaxis throughout treatment
- Monitor for CMV infection (positive PCR or antigen test) and discontinue treatment if any evidence of infection
- Monitor blood counts at least every 2 weeks for the first 6 months of treatment
- Increase monitoring to at least weekly if ANC < 1000/mm3
History of changes in FDA indication
Chronic lymphocytic leukemia - PARTIALLY WITHDRAWN
- 2014-07-23: FDA approved for the treatment of patients with relapsed chronic lymphocytic leukemia (CLL), in combination with rituximab, in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities. (Based on GS-US-312-0116)
- 2014-07-23: Accelerated approval for the treatment of patients with relapsed small lymphocytic lymphoma (SLL) in patients who have received at least two prior systemic therapies. (Based on DELTA)
- 2022-01-14: Accelerated approval for the treatment of patients with relapsed small lymphocytic lymphoma (SLL) in patients who have received at least two prior systemic therapies voluntarily withdrawn by the manufacturer. (No supporting studies are cited)
Follicular lymphoma - WITHDRAWN
- 2014-07-23: Accelerated approval for the treatment of patients with relapsed follicular B-cell non-Hodgkin lymphoma (FL) in patients who have received at least two prior systemic therapies. (Based on DELTA)
- 2022-01-14: Accelerated approval for the treatment of patients with relapsed follicular B-cell non-Hodgkin lymphoma (FL) in patients who have received at least two prior systemic therapies voluntarily withdrawn by the manufacturer. (No supporting studies are cited)
History of changes in EMA indication
- 2014-09-18: Initial authorization
- Zydelig is indicated in combination with an anti-CD20 monoclonal antibody (rituximab or ofatumumab) for the treatment of adult patients with chronic lymphocytic leukaemia (CLL) who have received at least one prior therapy.
- Zydelig is indicated in combination with an anti-CD20 monoclonal antibody (rituximab or ofatumumab) for the treatment of adult patients with chronic lymphocytic leukaemia (CLL) as first line treatment in the presence of 17p deletion or TP53 mutation in patients who are not eligible for any other therapies.
- Zydelig is indicated as monotherapy for the treatment of adult patients with follicular lymphoma (FL) that is refractory to two prior lines of treatment.
History of changes in Health Canada indication
- 2015-03-27: Initial notice of compliance with conditions
- 2020-04-21: Conditions were met
Also known as
- Code names: CAL-101, GS-1101
- Brand name: Zydelig
References
- ↑ 1.0 1.1 1.2 Idelalisib (Zydelig) package insert
- ↑ Idelalisib (Zydelig) package insert (locally hosted backup)
- ↑ Zydelig manufacturer's website
- ↑ S. E. Coutre, J. C. Byrd, R. R. Furman, J. R. Brown, D. M. Benson, N. D. Wagner-Johnston, I. W. Flinn, B. S. Kahl, S. E. F. Spurgeon, B. J. Lannutti, H. K. W. Hsu, R. Ulrich, S. Peterman, L. Holes, L. L. Miller, A. S. Yu. Phase I study of CAL-101, an isoform-selective inhibitor of phosphatidylinositol 3-kinase P110d, in patients with previously treated chronic lymphocytic leukemia. 2011 ASCO Annual Meeting abstract 6631.
- ↑ I. W. Flinn, J. C. Byrd, R. R. Furman, J. R. Brown, T. S. Lin, C. Bello, N. A. Giese, A. S. Yu. Preliminary evidence of clinical activity in a phase I study of CAL-101, a selective inhibitor of the p1108 isoform of phosphatidylinositol 3-kinase (P13K), in patients with select hematologic malignancies. 2009 ASCO Annual Meeting abstract 3543.
- ↑ Lannutti BJ, Meadows SA, Herman SE, Kashishian A, Steiner B, Johnson AJ, Byrd JC, Tyner JW, Loriaux MM, Deininger M, Druker BJ, Puri KD, Ulrich RG, Giese NA. CAL-101, a p110delta selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability. Blood. 2011 Jan 13;117(2):591-4. Epub 2010 Oct 19. PubMed