SEQUENTIAL TKI USE | IDENTIFYING TKI FAILURE

CONTROL OF CML MAY DIMINISH WITH SEQUENTIAL TKI USE

A UNIQUE MECHANISM

Learn more about how SYNRIBO® works   

STUDIED IN HEAVILY PRETREATED PATIENTS

See the study design for information on how SYNRIBO was evaluated   

TKIs are the standard of care in CML

Imatinib is recommended for newly diagnosed patients1

  • In the Interferon vs STI571 (IRIS) Study, the imatinib estimated 8-year overall survival rate was 85% (n=304)2

2nd-generation TKIs are also recommended in first line or following TKI failure1

While TKIs help control CML long term for many patients, resistance and intolerance may present challenges over time

Currently available TKIs cannot cure CML but can make it a manageable disease for most patients1,3

TKIs may be discontinued due to issues such as resistance, intolerance, suboptimal response, and progression1

Sequential TKI use

Clinical studies suggest that with each line of TKI use

  • Discontinuation rates may increase2,4-11
  • Time to discontinuation may decrease9-14

Indication

  • SYNRIBO® (omacetaxine mepesuccinate) for Injection, for subcutaneous use, is indicated for the treatment of adult patients with chronic or accelerated phase chronic myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors (TKIs). This indication is based upon response rate. There are no trials verifying an improvement in disease-related symptoms or increased survival with SYNRIBO

Important Safety Information

Warnings and Precautions

  • Myelosuppression: Patients with chronic phase and accelerated phase CML who used SYNRIBO experienced severe and fatal myelosuppression including thrombocytopenia, neutropenia, and anemia. Patients with neutropenia are at increased risk for infections, and should be monitored frequently and advised to contact a physician if they have symptoms of infection or fever. Monitor complete blood counts weekly during induction and initial maintenance cycles and every two weeks during later maintenance cycles, as clinically indicated
  • Bleeding: SYNRIBO causes severe thrombocytopenia which increases the risk of hemorrhage. Fatalities from cerebral hemorrhage have occurred. Severe, non-fatal gastrointestinal hemorrhages have also occurred. Monitor platelet counts as part of the complete blood count (CBC) monitoring as recommended. Avoid anticoagulants, aspirin, and nonsteroidal anti-inflammatory drugs (NSAIDs) when the platelet count is <50,000/μL as they may increase the risk of bleeding
  • Hyperglycemia: SYNRIBO can induce glucose intolerance. Monitor blood glucose levels frequently, especially in patients with diabetes or risk factors for diabetes. Avoid SYNRIBO in patients with poorly controlled diabetes mellitus until good glycemic control has been established
  • Embryo-fetal toxicity: SYNRIBO can cause fetal harm when administered to a pregnant woman. Women should be advised to avoid becoming pregnant while using SYNRIBO

Adverse Reactions

  • Serious adverse reactions (frequency ≥5%) in chronic phase patients: bone marrow failure, thrombocytopenia, febrile neutropenia, and infections
  • Serious adverse reactions (frequency ≥5%) in accelerated phase patients: febrile neutropenia, thrombocytopenia, anemia, diarrhea, convulsions, and infections
  • Most common adverse reactions (frequency ≥20%) in chronic and accelerated phase patients: thrombocytopenia, anemia, neutropenia, diarrhea, nausea, fatigue, asthenia, injection site reaction, pyrexia, infection, and lymphopenia
TO REPORT SIDE EFFECTS: Contact us at 1-800-896-5855 or USMedInfo@tevapharm.com
References
  1. National Comprehensive Cancer Network®. Clinical Practice Guidelines: Chronic Myelogenous Leukemia–v.4.2013. http://www.nccn.org/professionals/physician_gls/pdf/cml.pdf. Accessed April 2, 2013.
  2. Deininger M, O’Brien SG, Guilhot F, et al. International Randomized Study of Interferon vs STI571 (IRIS) 8-year follow up: sustained survival and low risk for progression or events in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with imatinib [ASH abstract 1126]. Blood. 2009;114.
  3. The Leukemia & Lymphoma Society. Chronic Myeloid Leukemia [patient guide]. 2012. http://www.lls.org/content/nationalcontent/resourcecenter/freeeducationmaterials/leukemia/pdf/cml.pdf. Accessed September 14, 2012.
  4. O’Brien SG, Guilhot F, Larson RA, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2003;348:994-1004.
  5. Kantarjian H, Shah NP, Hochhaus A, et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2010;362:2260-2270.
  6. Larson RA, Kim D, Rosti G, et al. Comparison of nilotinib and imatinib in patients (pts) with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP): ENESTnd 24-month follow-up [ASCO abstract 6511]. J Clin Oncol. 2011.
  7. Druker BJ, Guilhot F, O’Brien SG, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006;355:2408-2417.
  8. Kantarjian H, Pasquini R, Levy V, et al. Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia resistant to imatinib at a dose of 400 to 600 milligrams daily: two-year follow-up of a randomized phase 2 study (START-R). Cancer. 2009;115:4136-4147.
  9. Kantarjian H, Giles F, Gattermann N, et al. Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance. Blood. 2007;110:3540-3546.
  10. Quintas-Cardama A, Kantarjian H, Jones D, et al. Dasatinib (BMS-354825) is active in Philadelphia chromosome-positive chronic myelogenous leukemia after imatinib and nilotinib (AMN107) therapy failure. Blood. 2007;109:497-499.
  11. Giles FJ, Abruzzese E, Rosti G, et al. Nilotinib is active in chronic and accelerated phase chronic myeloid leukemia following failure of imatinib and dasatinib therapy. Leukemia. 2010;24:1299-1301.
  12. GLEEVEC (imatinib mesylate) Tablets for Oral Use Prescribing Information. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2012.
  13. TASIGNA (nilotinib) Capsules Prescribing Information. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2012.
  14. SPRYCEL (dasatinib) Tablet for Oral Use Prescribing Information. Princeton, NJ: Bristol-Myers Squibb Co; 2011.