Q&A With New Head of the Blood and Marrow Transplant and Cellular Therapy Program

A 20-year veteran of the Medical College of Wisconsin, Marcelo Pasquini, MD, joined Cleveland Clinic Cancer Institute as the New Director of the Blood and Marrow Transplant and Cellular Therapy Program. ConsultQD recently had an opportunity to talk with Dr. Pasquini about his plans for the center and what the future holds for cell and gene therapy.

Q. Can you share a bit about your vision for the Transplant and Cell Therapy Center?

With an average of 300 infusions a year for all sorts of transplants and cellular therapies, this is a well-established program that's always been at the forefront. Our plan is to steer and grow the program to serve more of the community. My vision is to continue to serve as a destination center that’s recognized nationally. That means not just attracting more patients but attracting talent and advancing caregivers’ careers.

We’re looking at multiple areas, such as our referral patterns, expansion of programs to improve access to these therapies as well as launching new clinical trials. We’re also looking at additional collaborations. We already work with outside providers who refer patients to us for CAR T-cell therapy or autologous transplants whereby the patients return to the referring physician a month or two after the procedure for care closer to home. We want to expand these collaborations.

Q. Can you talk a bit about your work with the Center for International Blood and Marrow Transplant Research?

I worked on the creation of a database to follow outcomes of CAR T-cell recipients. The database became a resource for the community at large, providing a service for long-term follow up of CAR T-cell recipients and a source of real-world data for research. As a scientific director, I served as a liaison between the database statisticians and the outside community. I was also involved in the development of several clinical trials in transplantation and CAR T-cell therapy.

Q. What are some of the greatest challenges today in cell and gene therapy?

First and foremost is the speed of change. These therapies are evolving so quickly, so the challenge is to adapt amid unprecedented growth and variability. Since the first CAR T-cell therapies became available there’s been a proliferation of their use, both expanding the label for new indications and using them earlier in the disease course on indications originally approved.

Having these therapies available in the clinical trial setting allows us to learn a great deal about how to care for these patients and manage side effects. Then when the therapies become available as standard of care, we’ll have a better sense of how to manage them and how best to deliver them safely.

Q. What advances in cell and gene therapy are you most excited about?

In terms of established therapies, we’re learning to make them safer. We're seeing products made not only from patients’ own cells but ones that are available off the shelf (also known as allogeneic CAR T cells). Those are not ready for clinical use yet, but we have them in clinical trials for different indications.

We also have trials using CAR T cells for treatment of patients with amyloidosis. These are similar to CAR T cells used for multiple myeloma. Expansion of their use to amyloidosis has demonstrated promising early results. Additionally, we're exploring the use of cell therapy for autoimmune diseases like multiple sclerosis (MS) and systemic lupus erythematous as a novel area of application of CAR T cells in autoimmune diseases.

In terms of gene therapy, there are approved therapies that correct gene defects or alter the natural history of conditions like sickle cell disease, thalassemias and hemophilia.

On the blood and marrow transplant front, many advancements resulted in an ongoing improvement of outcomes. We have many donor options, so it is very rare that we don’t find a donor for a patient. Also, newer approaches to reduce common transplant complications resulted in transplants with greater success.

Q. Can you discuss initiatives to manufacture CAR T cells here at Cleveland Clinic?

Point-of-care manufacturing of CAR T cells involves collecting the cells from the patient and manufacturing them in a lab within our own facility. It’s important to have this as part of our portfolio to contribute to scientific discovery on CAR T-cell manufacturing and to improve access for patients.

Doing so requires Good Manufacturing Procedure (GMP) rooms, which are necessary for developing and processing these cellular products. Cleveland Clinic’s Learner Institute was recently approved to construct three GMP rooms, and is doing so under the leadership of Dr. Melenhorst, who will be running clinical trials of point-of-care CAR T-cell products in the near future.

In the meantime, we’re collaborating on clinical trials with the Comprehensive Cancer Center at Case Western, which has active GMP facilities and active CAR T-cell point of-care-manufacturing. Currently, there are trials for treatment of lymphoma using these cellular products.

Q. How is the Transplant and Cellular Therapy Center working to improve the quality of life for patients undergoing these treatments?

The more we care for patients with these types of therapies, the more that side effects become predictable. This knowledge will make it possible to shift to providing these therapies on an outpatient basis for eligible patients. For some indications, we’re already able to deliver the initial chemotherapy and cellular infusion outpatient, with patients being admitted for monitoring five days later. This improves quality of life by reducing their hospital stay.

The next step is considering the possibility of performing entire cell therapy treatments outpatient. Another area of improvement we’re looking at is adjusting the amount of time that patients need to stay close to the hospital after CAR T-cell therapy. Decreasing the requirement from 28 days to 14 days allows patients to return home faster.

Q. Can you elaborate on where things stand in terms of CAR T-cell therapy for treating conditions like MS and lupus?

There is a big area of expansion in autoimmune diseases and neuroinflammatory illnesses like MS and myasthenia gravis. Our Cell Therapy Research Team (CTRT), led by Dr. Paolo Caimi, oversees trials of new and upcoming cell therapies, including CAR T-cell therapy, tumor infiltrating lymphocytes and T-cell receptor edited cells. We have a collaboration with the Mellon Center for Neurology for the study of diseases like MS and myasthenia gravis as well as collaboration with our Rheumatology Group for the treatment of lupus.

These collaborations enable hematologists and solid tumor oncologists to share expertise in the application of these treatments as well as safety management. The CTRT aims to be a resource to run clinical trials using cellular immunotherapy and gene therapies.