Rob Miani joined the MMRF team as Chief Financial Officer in 2016. Most recently he was the Vice President of Finance and Corporate Controller of Aptuit, LLC, a global contract research organization providing integrated early discovery to mid-phase drug development services in the pharmaceutical industry. Rob has over 20 years of leadership experience in the private and public sectors, holding managerial positions in the renewable energy, private equity, Internet and technology industries, including Davenport Newberry, Oak Investment Partners and INT Media Group. He began his career with Arthur Anderson LLP in the Assurance and Business Advisory Services Division. Rob is a CPA and received his BS degree in Accounting from Fairfield University.
The Difference Between Cellular Therapy and Autologous Stem Cell Transplant
Autologous stem cell transplantation (ASCT) and cellular therapies are among the options used to treat multiple myeloma. A major difference between these approaches is the type of cells used. ASCT uses a patient’s own stem cells (precursor cells that give rise to many types of blood cells), which are collected, stored, then returned to the patient after they receive high-dose chemotherapy. Cellular therapies mainly use a patient’s own T cells, which are a type of white blood cell that helps identify, target, and attack myeloma cells. To understand how these cell-based treatments are useful in treating multiple myeloma, it’s helpful to look at the differences between them.
Cellular Therapy or Adoptive Cell Transfer
In adoptive cell transfer, a patient’s own immune cells (usually T cells) are collected and taken to a laboratory, where they are engineered to be better at identifying and killing myeloma cells. The engineered cells are then infused back into the patient.
One of the most exciting and promising cellular therapies is called chimeric antigen receptor (CAR) T-cell therapy. In this type of therapy, the T cells are engineered in a new way: a specially developed receptor is added to their surfaces. This receptor makes the T cells better at targeting and attaching to certain proteins that are found on the surface of myeloma cells. The interaction between the engineered T cells—that is, the CAR T cells—and myeloma cells results in the destruction of the cancer cells. CAR T-cell therapies that target a protein called BCMA have generated a lot of interest recently. BCMA is a protein that is found on the surface of most myeloma cells, making it a good target for the modified T cells to latch onto.
ASCT and adoptive cell transfer are similar in that both approaches start with harvesting blood cells from the patient. Where these approaches differ is in what is done with the cells after they’ve been collected. In ASCT, the cells are stored until needed but are not modified in any way. In adoptive cell transfer, the harvested blood cells are altered in a lab using highly specialized techniques before being infused back into the patient. Preparing cells for adoptive cell transfer usually takes 2 to 3 weeks.
Adoptive cell transfer is still in the experimental phase for a number of cancers, including myeloma. However, the results in clinical trials have been encouraging and two CAR T-cell therapies have gained FDA approval so far—one for some patients with acute lymphoblastic leukemia and one for certain types of large B-cell lymphoma.
Adoptive cell transfer can have serious side effects, particularly in the period immediately following re-infusion of the cells to the patient. One common and serious side effect, called cytokine release syndrome, is a major concern. Cytokine release syndrome can occur after re-infusion of the altered T cells, and it causes fevers, chills, and low blood pressure. Another serious side effect is neurotoxicity, which is a type of damage to the brain that can cause confusion, seizures, or severe headaches. As scientists continue to study the potential use of these cutting-edge therapies in multiple myeloma, they are also seeking ways to reduce these side effects.
To learn more about CAR T-cell therapy, you can listen to Dr. Edward Stadtmauer here.
Autologous Stem Cell Transplantation
ASCT is used to treat not just multiple myeloma, but other types of blood cancer such as leukemia and lymphoma. It is also used for non-cancerous blood disorders, including some types of anemia. The idea behind ASCT is to use the patient’s own blood cells to help restore his or her blood supply and immune system after receiving melphalan, a drug that kills cancer cells but also kills blood-forming cells.
In the weeks leading up to the ASCT, after the patient receives induction therapy (the first in a series of treatments used to treat cancer), blood-forming stem cells are collected. Once the cells are collected, they are stored until the patient is ready for them to be re-infused. After the patient receives high-dose melphalan, the stem cells are infused back into the patient to complete the ASCT. In this way, the normal blood-forming cells that were destroyed by the melphalan are replaced. For patients who are eligible, ASCT can provide long and deep remissions (periods in which there no symptoms of myeloma or signs that any abnormal plasma cells are present). Thus, ASCT has become a mainstay of myeloma treatment. In some cases, more than one ASCT may be needed to get an adequate response and control disease.
ASCT can be performed as an inpatient (the patient stays in the hospital before, during, and immediately after the transplant) or outpatient (the patient makes daily visits to a clinic) procedure. This procedure can have a long recovery process, and there are many potential side effects associated with its use, including fatigue, nausea and vomiting, diarrhea, mouth sores (mucositis), and low blood counts. Many patients are at increased risk of infection following ASCT.
If you have questions about ASCT or cellular therapies or want to know if a CAR T-cell therapy trial is available near you—you can contact a Patient Navigator at the MMRF Patient Navigation Center at 888-841-6673.
Additional Resources
MMRF 2019 webinar: Emerging Immunotherapy Treatments in Myeloma: CAR T-Cell Therapy and BiTEs.
MMRF blog post: MMRF Immunotherapy Initiative: Chimeric Antigen Receptor (CAR) T-Cell Therapy.
MMRF webpage: Stem Cell Transplants.
MMRF Patient Kit: Treatment Overview Brochure.
