The advent of imatinib (Gleevec; Novartis Pharmaceuticals) was considered a near miracle for the treatment of chronic myeloid leukemia (CML). In the pre-imatinib era, life expectancy was short, but now the majority of patients with CML can live for many years on treatment with imatinib, and when it fails, second-generation tyrosine kinase inhibitors (TKIs) can extend life. However, a proportion of patients will eventually become resistant to all TKIs.
What option exists for patients in whom therapy with 2 or more TKIs fails? Synribo (omacetaxine mepesuccinate; Teva Pharmaceuticals) was approved by the US Food and Drug Administration for patients whose treatment with 2 or more prior TKIs has been unsuccessful or who are intolerant to these agents. In a proportion of these previously treated patients, Synribo has achieved durable responses.
Synribo is given twice a day via subcutaneous injection. It was approved for home use in 2014, making it more convenient.
At the 2015 annual meeting of the Oncology Nursing Society, Lisa Matta, RN, MSN, University of Arizona Cancer Center, Tucson, discussed issues related to the use of Synribo in patients with CML. Her presentation was supported by Teva Oncology, the company that markets Synribo.
As with any drug, Synribo has risks and benefits. Warnings for this agent in patients with CML include myelosuppression (thrombocytopenia, neutropenia, and anemia).
Patients receiving Synribo should have blood count monitoring during induction, maintenance, and every 2 weeks thereafter, Matta told listeners. The drug can cause bleeding, so patients taking Synribo should avoid aspirin or other blood thinners. “Synribo has been associated with fatal and nonfatal hemorrhages. Monitor those blood counts!” she emphasized.
Hyperglycemia is another adverse event (AE) that can occur. Patients should have their diabetes under control before initiating Synribo, she advised.
Treatment-related common AEs in chronic-phase CML include bone marrow failure, thrombocytopenia, neutropenia, and infections; in accelerated-phase CML, treatment-related AEs include febrile neutropenia, anemia, diarrhea, and infections.
The most common AEs, occurring in >20% of patients, are thrombocytopenia, neutropenia, injection-site reactions, pyrexia, and lymphopenia.
CML is a myeloproliferative disorder that originates in hematopoietic stem cells. The natural history of the disease includes 3 phases: chronic, accelerated, and blast crisis. In most patients with CML, the Philadelphia chromosome is present. TKI treatment regulates BCR-ABL, a constitutively active tyrosine kinase in CML. BCR-ABL may be present even after TKI treatment.
Response to treatment is assessed by BCR-ABL levels, and is defined as complete hematologic response (CHR), complete cytogenic response (CCyR), major cytogenic response (MCyR), and major molecular response (MMR).
TKIs are the standard of care for patients with CML. First-line treatment with imatinib is associated with an 8-year survival rate of 85%. Second-generation TKIs (dasatinib, nilotinib, bosutinib) can be used following failure on another TKI. Eventually, most patients with CML will develop resistance to TKIs, and that is where Synribo comes into play.
Clinical trials have established the efficacy of Synribo in patients in whom TKI therapy has failed. In one study of 76 patients who received Synribo after unsuccessful treatment with 2 prior TKIs, MCyR was 18%. In responders, mean time to response was 3.5 months and mean duration of response was 12.5 months.
“Some patients have long-lasting responses to Synribo, allowing them to resume their lives and even travel,” Matta said.
Pooled safety data from 3 clinical trials of Synribo showed that AEs occurred in 99% of patients; 18% had AEs leading to withdrawal.
Patient Instructions for Home Use
Teva provides written and telephone support for patients who use Synribo at home. The patient education website includes a video with instructions for home use. If they have questions, patients can call 1-844-SYNCare 24 hours a day.
Synribo comes predosed, along with a biohazard container, gloves, goggles, syringes, and absorbent pads to wipe up spills. It can be stored at room temperature for 12 hours or for 6 days in the refrigerator.
The first dose of Synribo is always given in a doctor’s office by a healthcare professional, Matta said.
At home, the patient should wear goggles and gloves during administration. The biohazard container should be used for needles and syringes, as well as for any wipes or gloves that come in contact with the drug.
Matta L. Treatment considerations for chronic myeloid leukemia (CML) adult patients after multiple tyrosine kinase inhibitor (TKI) failures. Presented at: Oncology Nursing Society 40th Annual Congress; April 22-26, 2015; Orlando, FL.