Optimizing CAR T-Cell and Stem Cell Transplant Treatments

New BMT leadership looks to clinical research and cell therapy production to overcome treatment access limitations

Cell-based gene therapies such as CAR T-cell therapy have generated tremendous excitement in the medical community, but this has been tempered of late, due to shortcomings in treatment access and other barriers. For hematology experts like Craig Sauter, MD, that situation is untenable. He joined Cleveland Clinic early this year after serving as the clinical director of the Adult Bone Marrow Transplant (BMT) Service at Memorial Sloan Kettering Cancer Center, where his research focused on the use of new transplant approaches for treating non-Hodgkin lymphomas, chronic lymphocytic leukemia and other hematologic malignancies.

Advertising Policy

Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services Policy

As the new Director of the Blood and Bone Marrow Transplant program at Cleveland Clinic, he is leading efforts to overcome obstacles to care and to improve the lives of patients with blood cancers.

“National Marrow Donor Program data shows that in many areas of the country, patients are indicated for transplantation but are not able to access the treatment for a multitude of reasons, whether it’s resources, health equity or issues receiving the appropriate referral to a tertiary care center like Cleveland Clinic for evaluation,” says Dr. Sauter. “The same goes for CAR T-cell therapy. What we’re learning in the multiple myeloma space is that despite there being two FDA-approved CAR T-cell therapies for the disease, the manufacturing of the product can’t keep up with the demand.”  

Even patients who receive a coveted slot for CAR T-cell therapy typically must wait weeks for the product to be manufactured. This is time that many patients with aggressive disease simply cannot spare.

Tackling health inequities for patients with blood cancer

To augment FDA-approved treatments, the BMT Program is actively investigating alternative new agents that have shown promise in the lab. CAR T-cell therapy was proof of principle of cell therapy, yet in far too many cases, remission is still not long-lasting. Dr. Sauter and his colleagues are working to achieving optimal outcomes for all patients receiving this therapy. They hope to build on this success to develop more enhanced first- and second-generation cellular therapies as well as augmenting this therapy with adjunctive drug therapies.

One very promising development is a move to create homegrown, unique cell products and to build a cellular therapy production facility within Cleveland Clinic. This would greatly enhance the institution’s ability to accelerate treatment and increase the number of patients who can benefit from it.

Advertising Policy

Dr. Joseph Melenhorst was recruited by the Lerner Research Institute and the Center for Immunotherapy & Precision Immuno-Oncology here at Cleveland Clinic,” says Dr. Sauter. “He’s a very successful laboratory-based cellular therapy scientist. We intend to work closely together from bench to bedside to learn from patients’ experiences and develop new products that he’s working on in the lab.”

To increase treatment access, the BMT team is also intending to transition many therapies to the ambulatory, outpatient setting so that younger, healthier patients who are candidates for autologous stem cell transplants can potentially receive treatment without a hospital stay. This would both improve patient satisfaction and alleviate utilization of inpatient resources.

Managing drug toxicities

Another challenge Dr. Sauter and his team are keenly focused on is minimizing toxicities associated with hematology treatments. ”There are still far too many treatment-related mortalities,” says Dr. Sauter. “It’s really difficult to accept when patients die of complications of treatment, despite being in remission from their cancer. We plan to broaden the portfolio of investigational therapies, particularly within cellular therapy and transplant, to make treatments safer and more effective.”

Expanding existing cell therapy

The BMT Center is conducting retrospective research into patients being treated with commercially available CAR T-cell and related therapies, and building prospective studies going forward. This includes researching adoptive cell therapy for the treatment of blood cancers. This approach may make it possible in the future for engineered cells to actually be able to produce drugs. Working at the level of the microenvironment of a tumor, investigators are learning how cellular therapy behaves within the microenvironment so they can manipulate cellular elements that inhibit the effects of CAR T-cells or immune effector cells.

Though the CAR T-cell therapies that are FDA approved thus far have proven successful exclusively in blood cancers such as lymphoma, leukemia and multiple myeloma, investigators at Cleveland Clinic are also studying whether these treatments could be effective for solid organ malignancies. A Phase I, open-label, multicenter study of FT536 as monotherapy and in combination with monoclonal antibodies will soon be enrolling patients with advanced non-small cell lung, colorectal, breast, ovarian, pancreatic, head and neck and gastroesophageal cancers.

Advertising Policy

Expanding treatment and trial access globally

Though the main campus is currently the only Cleveland Clinic site conducting hematopoietic transplants and cellular therapies, the plan is that this won’t be the case for long. Dr. Sauter intends to help develop a program in South Florida where there is a large, unmet need for transplantation. The next big initiative is to establish a similar program at Cleveland Clinic Abu Dhabi where patients could receive immune effector cell therapies, including CAR T-cell treatment, and hopefully have the opportunity to join pivotal clinical trials.

Part of the bigger vision at Cleveland Clinic is to have more patients around the world participate in evaluating promising new agents so investigators can get answers to research questions faster. “Cancer medicine is moving so fast that studies need to be conducted faster to get to the answers we need, quickly,” says Dr. Sauter. “We might have an exciting study but if it takes years to get patients enrolled, let alone to follow-up their progress, the results may be less relevant in 5-10 years. Accelerating clinical trial accrual is crucial for this reason.”

The BMT Program is also collaborating with University Hospitals and MetroHealth the Case Comprehensive Cancer Center to optimize the science and treatment of patients with cancers through cellular therapy, including blood transplantation.

“Many patients are faring better with cellular therapy than they were with previous treatments, but that doesn’t mean we can rest on our laurels,” says Dr. Sauter. “We know that we can deliver this therapy with the intent to cure but we have a long way to go in curing most patients. That’s why it’s a priority for us to be part of the innovation of developing new cellular therapies and modalities of transplantation so that we’re not just helping the patients we treat, but contributing to knowledge to help patients beyond the boundaries of Cleveland Clinic.”