Sprycel® Therapy for Chronic Myeloid Leukemia

Cancer Connect

by Dr. C.H. Weaver M.D. updated 3/2020

According to results recently presented at the 2007 annual meeting of the American Society of Clinical Oncology (ASCO), Sprycel® (dasatinib) is an effective treatment option when used as initial therapy among patients with Ph-positive chronic myelogenous leukemia (CML).

Chronic myelogenous leukemia is a cancer that originates in the immune cells. It affects approximately 4,600 people annually in the U.S. In the case of CML, large numbers of young immune cells do not mature, resulting in an excess accumulation of these cells. These leukemia cells then crowd the bone marrow and blood, suppressing formation and function of other blood cells normally present in these areas. In addition, the leukemia cells cannot perform their function properly, leaving patients susceptible to infection.

Chronic myelogenous leukemia begins with a chronic phase, during which few clinical problems, if any, occur. However, when left untreated, the chronic phase progresses into acute phases; these phases, called the accelerated and blastic phases, are characterized by fast-growing and aggressive cancer. Patients reaching these acute phases have a poor prognosis for long-term survival.

Philadelphia chromosome-positive (Ph-positive) CML refers to the majority of cases of CML in which a genetic abnormality, referred to as the Philadelphia chromosome, results in the constantly activated growth of cancer cells. Roughly 30% of adult patients with acute lymphocytic leukemia (ALL) also have this genetic abnormality.

About Sprycel

Sprycel is an oral tyrosine kinase inhibitor reducing the activity of the BCR-ABL, SRC family, c-KIT, EPHA2, and PDGFR kinases by halting the production of proteins involved in cancer growth. Sprycel is approved by the U.S. Food and Drug Administration for treatment of Philadelphia chromosome-positive leukemia and is also indicated for the treatment of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy.

To compare Gleevec and Sprycel for the initial treatment of CML, researchers conducted a study among 519 patients with newly diagnosed, Philadelphia chromosome-positive, chronic-phase CML. Patients were assigned to receive either Gleevec or Sprycel.One of the main outcomes of interest was the complete cytogenetic response rate. A complete cytogenetic response is the complete disappearance of cells with the Philadelphia chromosome.

  • After one year, the complete cytogenetic response rate was 77% among patients treated with Sprycel and 66% among patients treated with Gleevec.
  • Rates of major molecular response (another marker of drug effectiveness) were 46% among patients treated with Sprycel and 28% among patients treated with Gleevec.
  • Both drugs were generally well tolerated.

These results suggest that Sprycel may be more effective than Gleevec for the initial treatment of CML. Researchers will continue to follow the study participants in order to determine whether there are differences in progression-free and overall survival between study groups.(2)

Sprycel in Gleevec Resistant CML

Researchers affiliated with the START-R trial recently conducted a study to compare Sprycel to increased doses of Gleevec among patients with CML who had stopped responding to standard doses of Gleevec. This study included patients with chronic-phase CML who had stopped responding to prior therapy with Gleevec. These patients were subsequently treated with either Sprycel or increased doses of Gleevec.

  • Among patients who had achieved a major cytogenetic (chromosomal) anticancer response with previous therapy including standard-dose Gleevec, 35% achieved a complete cytogenetic response to Sprycel, compared with only 7% of those treated with escalated doses of Gleevec.
  • Among patients who did not achieve a cytogenetic anticancer response with standard-dose Gleevec, 44% achieved a major cytogenetic response to Sprycel, compared with only 7% of those treated with escalated doses of Gleevec.
  • No patients who crossed over from the Sprycel group to the higher-dose Gleevec group demonstrated a major cytogenetic response; however, 45% of patients who crossed over from the higher-dose Gleevec group to the Sprycel group demonstrated a major cytogenetic response.
  • The main side effect of Sprycel was low levels of blood cells, which may be partly corrected with the use of Neulasta.

The researchers concluded that Sprycel provides superior responses compared to increased-doses of Gleevec among patients with chronic-phase CML who have stopped responding to prior therapy with standard-doses of Gleevec. Patients with CML who have stopped responding to Gleevec may wish to speak with their physician regarding their individual risks and benefits of treatment with Sprycel. (4)

Pediatric CML

Astudy evaluated 113 pediatric patients and is the largest prospective trial of pediatric patients with CML, offered at 80 medical centers in 18 countries.

Overall 75% of these patients who had previously failed or did not tolerate Gleevec saw improved progression-free survival 48 months after starting treatment with Sprycel. Of newly diagnosed pediatric patients who were previously untreated more than 90% saw progression-free survival at 48 months of beginning Sprycel treatment. In addition to the ability of Sprycel to control CML, it appeared to work very quickly. Within 3 months of beginning Sprycel treatment more than 50% of patients who had previously failed Gleevec responded to treatment.

Reference:

  1. Shah N, Pasquini R, Rousselot P, et al. Dasatinib (Sprycel®) vs escalated dose of imatinib (im) in patients (pts) with chronic phase chronic myeloid leukemia (CP-CML) resistant to imatinib: Results of the CA180-017 START-R randomized study. Proceedings from the 2006 annual meeting of the American Society of Hematology. December 2006. Blood. 2006;108:53a. Abstract 167.
  2. Kantarjian H, Shah NP, Hochhaus A et al. Dasatinib compared to imatinib in patients with newly diagnosed chronic-phase chronic myelogenous leukemia in chronic phase (CML-CP): 12 month efficacy and safety from the phase 3 DASISION study. Presented at the 2010 annual meeting of the American Society of Clinical Oncology. June 4-8, 2010. Chicago, IL. Abstract LBA 6500.
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  4. Shah N, Pasquini R, Rousselot P, et al. Dasatinib (Sprycel®) vs escalated dose of imatinib (im) in patients (pts) with chronic phase chronic myeloid leukemia (CP-CML) resistant to imatinib: Results of the CA180-017 START-R randomized study. Proceedings from the 2006 annual meeting of the American Society of Hematology. December 2006. Blood. 2006;108:53a. Abstract 167.

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