Autologous stem cell transplantation (SCT) is one treatment procedure for multiple myeloma, non-Hodgkin lymphoma, and Hodgkin lymphoma that has shown clinical success. However, there is room for improvement in the efficacy of this treatment. Researchers at Barbara Ann Karmanos Cancer Institute believe that one way of improving SCT is to administer dasatinib to patients in the 3 to 15 month time frame following SCT. This hypothesis is currently under scrutiny in the recruiting clinical trial, “Dasatinib for Modulating Immune System After Autologous Stem Cell Transplants for Multiple Myeloma, Non-Hodgkin, or Hodgkin Lymphoma.”
“This study uses a drug called dasatinib to produce an anti-cancer effect called large granular lymphocyte cellular expansion,” explained Abhinav Deol, MD, principal investigator at Barbara Ann Karmanos Cancer Institute. “Large granular lymphocytes are blood cells known as natural killer cells that remove cancer cells.” According to an article from a transplantation center in France, patients who develop large granular lymphocytes following SCT are more likely to achieve long-term complete remission, perhaps due to the immunoregulatory behavior of these cells.
Dasatinib, which is manufactured by Bristol-Myers Squibb as SPRYCEL, is indicated to treat chronic myeloid leukemia (CML), a type of leukemia characterized by an uncontrollable high number of abnormal blood cells that develops slowly over time. According to Bristol-Myers Squibb, growth seems to be driven by an abnormal protein named BCR-ABL, which signals the bone marrow to unnecessarily produce more white blood cells. SPRYCEL reduces CML cell growth by reducing the activity of BCR-ABL.
Another effect of dasatinib may be to increase large granular lymphocyte cellular expansion. According to literature from the First Affiliated Hospital of Nanjing Medical University, entitled “Large Granular Lymphocytosis During Dasatinib Therapy,” dasatinib treatment and subsequent increase in lymphocyte cellular expansion helps to eliminate residual leukemic cells, allowing patients to recover more fully from their lymphoma.
To continue testing this hypothesis, 30 patients will be treated with open-label dasatinib to find an optimal, tolerable dose. Patients will be monitored for dose limiting toxicity and the number of large granular lymphocytes developed after six months. Treatment will progress from 20 to 100 mg in 20-mg dose increments, or five doses with three patients in each cohort. All patients will be treated within 100 or 180 days after SCT. After a maximum safe tolerated dose is found, additional clinical trials may be pursued.
Those interested in learning more or participating in the trial can go here.