A Phase III clinical trial led by physicians in the US has shown that adding investigational drug motixafortide significantly increases the number of stem cells that can be harvested compared with treatment with the standard agent alone.
The standard treatment for patients with multiple myeloma often includes stem cell transplantation in which the patient’s own stem cells are harvested and stored while the patient receives intensive chemotherapy to kill the cancer. The stem cells are then returned to the patient to help with recovery.
However, for a significant proportion of patients, the number of stem cells that can be harvested is not optimal for transplant.
Senior author John F DiPersio, the Virginia E & Sam J Golman Professor of Medicine, Washington University School of Medicine, said: “This study suggests motixafortide works extremely well in combination with the standard drug, granulocyte colony stimulating factor (G-CSF), in mobilising stem cells in patients with multiple myeloma. The study also found that the combination worked rapidly and was generally well-tolerated by patients. We are hopeful that this investigational drug, if approved, will expand the number of patients who can receive an effective stem cell transplant for multiple myeloma.”
A huge increase in stem cells
A minimum of two million stem cells per kilogram body weight are necessary for a stem cell transplant in patients with multiple myeloma, but greater than five million to six million stem cells per kilogram body weight is considered optimal.
According to the researchers, the investigational drug motixafortide, when used in combination with the standard stem cell therapy, G-CSF, allowed optimal numbers of stem cells to be harvested in over 92% of patients after two collection procedures, compared with only 26% of patients who received G-CSF plus a placebo.
Even after just one collection procedure, the data showed that optimal stem cell numbers could be collected from 88% of patients who received motixafortide plus G-CSF, compared with only 9% of patients who received standard G-CSF plus a placebo.
Compared with standard therapy alone, the researchers also found that stem cells harvested with motixafortide in combination with G-CSF showed a tenfold increase in the number of primitive stem cells that could be collected. Primitive stem cells have greater potential to develop into a wider variety of blood cell types.
Stem cells mobilised by motixafortide also showed increased expression of genes and genetic pathways associated with self-renewal and regeneration, all beneficial for increased effectiveness of a stem cell transplant.
Research in sickle cell anaemia
The researchers also are evaluating motixafortide’s potential to support the genetic correction of the inherited disease sickle cell anaemia. Patients with sickle cell disease can’t be treated with G-CSF, due to dangerous side effects, including blocked blood vessels, organ failure and death.
The hope is that development of a novel, effective and well-tolerated stem cell mobilising regimen for a viral-based gene therapy approach using CRISPR-based gene editing will lead to improved outcomes for patients with sickle cell disease.