Tki 258 clinical trial after lenalidomide dex
This presentation is the property of its rightful owner.
Sponsored Links
1 / 16

TKI-258 Clinical Trial After Lenalidomide/Dex PowerPoint PPT Presentation


  • 78 Views
  • Uploaded on
  • Presentation posted in: General

TKI-258 Clinical Trial After Lenalidomide/Dex. Sundar Jagannath, MD St. Vincent's Comprehensive Cancer Center New York, NY. Thalidomide/Dexamethasone (Thal/Dex) as Primary Induction Therapy. ECOG phase 3 clinical trial (EA100) 207 newly diagnosed MM patients Response rate: Thal/dex: 63%

Download Presentation

TKI-258 Clinical Trial After Lenalidomide/Dex

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

Presentation Transcript


Tki 258 clinical trial after lenalidomide dex

TKI-258 Clinical Trial After Lenalidomide/Dex

Sundar Jagannath, MDSt. Vincent's Comprehensive Cancer CenterNew York, NY


Thalidomide dexamethasone thal dex as primary induction therapy

Thalidomide/Dexamethasone (Thal/Dex) as Primary Induction Therapy

  • ECOG phase 3 clinical trial (EA100)

    • 207 newly diagnosed MM patients

  • Response rate:

    • Thal/dex: 63%

    • Dex alone: 41%

    • p=0.0017

ECOG = Eastern Cooperative Oncology Group; MM = multiple myeloma;Thal = thalidomide 200 mg po qd; Dex = 40 mg po d1-4, 9-12,17-20

Rajkumar et al. J Clin Oncol. 2006;24(3):431-436.


Thalidomide dexamethasone as primary induction therapy

Thalidomide/Dexamethasone as Primary Induction Therapy

  • Incidence of DVT:

    • Thal/dex: 17%

    • Dex alone: 3%

  • DVT prophylaxis not included in trial design

  • Thal/dex did not compromise successful harvest of stem cells

DVT = deep vein thrombosis

Rajkumar et al. J Clin Oncol. 2006;24(3):431-436.


Thal dex as initial therapy time to progression ttp

1.0

0.8

0.6

0.4

0.2

0

6

12

18

24

30

Thal/Dex as Initial TherapyTime-to-Progression (TTP)

Thalidomide/dexamethasone Median TTP: not reached

Dexamethasone alone Median TTP: 8.1 months

Proportion of Patients

p<0.0001

Time-to-Progression (months)

Rajkumar et al. ASCO 2006, Abstract 7517.


High dose therapy with autologous stem cell transplant

High-dose Therapy WithAutologous Stem Cell Transplant

  • Treatment of choice for patients with refractory disease

  • Likelihood of long-term remission is low


Patient has poor prognostic indicators

Patient Has Poor Prognostic Indicators

  • IgA isotype

  • del(13q)

  • t(4;14)

IgA = immunoglobulin A; del(13q) = deletion of the long arm of chromosome 13


Treatment options for relapsed refractory disease

Treatment Options for Relapsed/Refractory Disease

  • Participation in a clinical trial

  • Allogeneic stem cell transplant

    • Morbidity/early mortality rates high

  • Combination therapy with bortezomib

    • Patient had relapsed after 8 cycles

  • Lenalidomide/dexamethasone is a viable option*

* Patients who have received at least one prior therapy


Len dex vs dex alone phase 3 trial mm 009 response

Len/Dex vs Dex Alone Phase 3 Trial(MM-009): Response

59.4%*

Response Rate (%)

* p<0.001

21.1%*

Bladè Criteria

Weber et al. ASCO 2006, Abstract 7521.


Mm 009 interim analysis time to progression

0

6

12

18

24

30

Time-to-Progression (months)

MM-009: Interim AnalysisTime-to-Progression

1.0

Len/Dex

Dex/Placebo

0.8

0.6

Med. 11.1 mo

Proportion of Patients

0.4

p<0.0001

0.2

Med. 4.7 mo

0.0

Weber et al. ASCO 2006, Abstract 7521.


Mm 009 overall survival

0

6

12

18

24

30

Overall Survival (months)

MM-009: Overall Survival

1.0

LEN/DEX

Med OS 29.6 mo

0.8

0.6

Proportion of Patients

DEX/PLACEBO

0.4

p<0.0001

Med OS 20.2 mo

0.2

0.0

Weber et al. ASCO 2006, Abstract 7521.


Len dex is more effective than dex placebo regardless of prior thalidomide

Len/Dex Is More Effective Than Dex/Placebo Regardless of Prior Thalidomide

TTP=Time-to-progression, OR=Overall Response, L=Lenalidomide, D=Dexamethasone

Wang et al. ASCO 2006, Abstract 7522.


Len dex mm 009 common adverse events

Len/Dex Grade 1-2

Len/Dex Grade 3-4

Dex Gr 1-4

Len/Dex (MM-009): Common Adverse Events

Constipation

Diarrhea

Nausea

URI

Pneumonia

Neutropenia

Anemia

Thrombocytopenia

Fatigue

Hyperglycemia

DVT/PE

Per. Neuropathy

0

10

20

30

40

50

60

70

% Patients

Weber et al. ASCO 2006, Abstract 7521.


Treatment recommendation

Treatment Recommendation

  • Lenalidomide/dexamethasone

  • Dosing schedule

    • Lenalidomide 25 mg, Days 1 to 21

    • High-dose dexamethasone (40 mg)*, Days 1 to 4, 9 to 12, and 17 to 20

    • Cycle repeated every 28 days

* After 4 cycles, dex schedule reduced to 40 mg on Days 1 to 4 per cycle.


Treatment alternatives

Treatment Alternatives

  • Re-induction with DCEP

    • Likelihood of achieving a durable remission is low

  • Second autologous SCT

    • Meaningful remission unlikely

    • High potential morbidity

  • Enrollment in a clinical trial for FGFR3 inhibitor

DCEP = dexamethasone, cyclophosphamide, etoposide, and cisplatin SCT = stem cell transplant


Phase 1 tki 258 chir 258 study

Phase 1 TKI-258 (CHIR-258) Study

  • TKI-258

    • Small-molecule inhibitor of FGFR3 and other receptor tyrosine kinases (RTKs)

  • FGFR3 is constitutively activated in patients with t(4;14)

FGFR3 = fibroblast growth factor receptor 3

Trudel et al. Blood. 2005;105(7):2941-2048; ClinicalTrials.gov, http://clinicaltrials.gov/ct/gui/show/NCT00243763?order=1?


Fgfr3 in multiple myeloma

FGFR3 in Multiple Myeloma

  • Role of activated FGFR3 in myeloma:

    • Promotes proliferation and survival of myeloma cells

    • Subsequent acquisition of activating FGFR3 mutations is associated with progression to late-stage myeloma

    • Can impart chemoresistance

  • TKI-258 may be an appropriate choice

Trudel et al. Blood. 2005;105(7):2941-2048


  • Login