Paul J. Shaughnessy, MD

Paul J. Shaughnessy, MD, hematologist, oncologist, and medical director of Adult Blood and Marrow Transplant Program at the Methodist Hospital, discusses the challenges faced with CAR T-cell therapy in hematologic malignancies.

The biggest challenge seen with CAR T-cell therapy is that the patients who need this treatment can be very sick; if they have relapsed/refractory disease, it can be rapidly growing, says Shaughnessy. Some of these patients do not have time to have their own lymphocytes collected, genetically engineered, and grown into these CAR T cells.

As such, these patients might not be able to receive treatment with this modality in a timely manner, according to Shaughnessy. However, efforts are being made to overcome this challenge. Experimental methods are being used to develop CAR T-cell therapy from allogeneic donors, allowing the CAR T-cells to be available off the shelf or in a more rapidly accessible; this would allow for more patients to receive treatment more quickly.

Also, many patients with these very advanced cancers will relapse, this needs to be addressed by making better CAR T-cell therapies, says Shaughnessy. Different strategies to achieve this may include making the CAR T cells target 2 antigens instead of just 1, augmenting the therapy with other agents that may increase the immune response, or using radiation to treat relapses before or after the treatment. The field is going to see many advances made in the future, making these therapies more readily available and more effective in patients with hematologic malignancies, concludes Shaughnessy.

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Paul J. Shaughnessy, MD, discusses the challenges faced with CAR T-cell therapy in hematologic malignancies.

Dr. Shaughnessy on Addressing Challenges With CAR T-Cell Therapy in Hematologic Malignancies

Paul J. Shaughnessy, MD, hematologist, oncologist, and medical director of Adult Blood and Marrow Transplant Program, at the Methodist Hospital, discusses challenges with CAR T-cell therapy in relapsed/refractory hematologic malignancies.

Often, patients who require CAR T-cell therapy have experienced multiple relapses, are refractory to available treatments, and have rapidly growing disease, says Shaughnessy. Moreover, in some cases, patients are unable to wait for their lymphocytes to be collected, engineered, and grown into CAR T cells.

Improving time-to-treatment with CAR T-cell therapy is an area of significant development, adds Shaughnessy. For example, allogeneic CAR T cells are a potential off-the-shelf option that would allow the product to be offered more readily.

Another challenge is preventing patients from relapsing following CAR T-cell therapy, Shaughnessy says. Some potential strategies to increase the durability of the therapy include dual-targeting antigens and augmenting CAR T with immunotherapy or radiation.

Paul J. Shaughnessy, MD, discusses challenges with CAR T-cell therapy in relapsed/refractory hematologic malignancies.  



Dr. Shaughnessy on Challenges With CAR T-Cell Therapy in Hematologic Malignancies 

Paul J. Shaughnessy, MD, hematologist, oncologist, and medical director of Adult Blood and Marrow Transplant Program, at the Methodist Hospital, discusses the promising future of CAR T-cell therapy in relapsed/refractory hematologic malignancies.

Patients with relapsed/refractory disease have always been a difficult-to-treat patient population, says Shaughnessy, who adds that it may be beneficial to move effective therapies into earlier-line settings.

To date, ongoing randomized studies are comparing the safety and efficacy of CAR T-cell therapy with other standards of care in both non-Hodgkin’s lymphoma and multiple myeloma.

Many are hopeful that, over time, these trials will transform the armamentarium in hematologic oncology, allowing patients to be treated more effectively with fewer adverse effects, Shaughnessy concludes.

Paul J. Shaughnessy, MD, discusses the promising future of CAR T-cell therapy in relapsed/refractory hematologic malignancies.

Dr. Shaughnessy on the Promise of CAR T-Cell Therapy in Hematologic Malignancies

Paul J. Shaughnessy, MD, hematologist, oncologist, and medical director of Adult Blood and Marrow Transplant Program at the Methodist Hospital, discusses the emergence of CAR T-cell therapy in hematologic malignancies.

CAR T-cell therapy ​has demonstrated encouraging activity in adults with relapsed/refractory non-Hodgkin lymphoma and pediatric patients with relapsed/refractory acute lymphoblastic leukemia, says Shaughnessy

​Several ongoing studies are​ evaluating CAR T-cell therapy ​in multiple myeloma and other ​types of lymphoma, explains Shaughnessy. Moreover, the encouraging results observed thus far ​suggest that CAR T-cell therapy will receive regulatory approval in additional indications in the future.

Beyond the hematologic space, CAR T-cell therapy could ​have utility in solid tumors, Shaughnessy concludes.

Paul J. Shaughnessy, MD, discusses the emergence of CAR T-cell therapy in hematologic malignancies.

Dr. Shaughnessy on the Emergence of CAR T-Cell Therapy in Hematologic Malignancies

Paul J. Shaughnessy, MD, hematologist, oncologist, and medical director of Adult Blood and Marrow Transplant Program at the Methodist Hospital, discusses the available CAR T-cell therapies for relapsed/refractory hematologic malignancies.

There are 2 CAR T-cell products that are commercially available now, says Shaughnessy: axicabtagene ciloleucel (axi-cel; Yescarta) and tisagenlecleucel (Kymriah). These products are available for adults with relapsed/refractory diffuse large B-cell lymphoma who have failed all standard therapies. There has been a gap in the availability of treatment for these patients.

CAR T-cell therapies now provide very meaningful responses in these patients, some of which have been very durable for a number of months, or even years. CAR T-cell therapies are very important in filling this gap in patients with relapsed/refractory lymphoma, as well as in pediatric patients with relapsed/refractory acute lymphoblastic leukemia. Once again, there is no standard therapy for this population, though CAR T-cell therapy is offering durable remissions in a percentage of these patients, concludes Shaughnessy.

Paul J. Shaughnessy, MD, discusses the available CAR T-cell therapies for relapsed/refractory hematologic malignancies.

Paul J. Shaughnessy, MD

Articles

Dr. Shaughnessy on Addressing Challenges With CAR T-Cell Therapy in Hematologic Malignancies

Dr. Shaughnessy on Challenges With CAR T-Cell Therapy in Hematologic Malignancies

Dr. Shaughnessy on the Promise of CAR T-Cell Therapy in Hematologic Malignancies

Dr. Shaughnessy on the Emergence of CAR T-Cell Therapy in Hematologic Malignancies

Dr. Shaughnessy on Available CAR T-Cell Therapies in R/R Hematologic Malignancies