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Dr. Utkarsh Acharya: On the Challenges, Pride and Frustrations of Treating CAR-T Patients

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Utty and me

I recently introduced you to one of the fine doctors who cared for me at the Seattle Cancer Care Alliance (SCCA) and University of Washington Medical Center (UWMC) – Dr. Utkarsh Acharya.

Dr. Utkarsh H. Acharya, DO, FACP is now the Program Director, Hematology-Oncology Fellowship Program, DFCI (Dana Farber Cancer Institute)/SEMC(St Elizabeth’s Medical Center) and an Attending Physician, Hematologic Malignancies, Dana Farber Cancer Institute and an Attending Physician, Cellular Therapy, Brigham & Women’s Hospital.

Here is the second part of my interview with him on CAR-T therapy.

What do you see as your biggest challenges in CAR-T therapy as of today?

CAR-T cell therapy has the potential to generate excellent response rates with durable remissions in a wide spectrum of hematologic malignancies as we have seen over the recent years. However, as you note, it certainly does come with a considerable number of challenges. In my opinion, several of the challenges include improving the laborious manufacturing process to shorten the time from leukapheresis (cell collection) to administration of the engineered cells (especially since so many CAR-T patients have rapidly progressing disease), creating novel ways of mitigating CAR-T cell mediated toxicities such as cytokine release syndrome (CRS) and/or neurotoxicity, and improving not just general response rates but the depth of response. Lastly, even though CAR-T cells are useful in various blood cancers, their reliable efficacy in solid tumors is still limited and thus also poses a challenge.

What are you most proud of in your immunotherapy work?

I think the biggest pride that I have in my work stems from my patients that are willing to serve as pioneers and be on the forefront of advancing medicine. As a field, colleagues have come together to improve prognostication of various cancers through genomic/molecular profiling, identified novel treatment pathways, and advanced in transnational research to bring cancer therapy from the lab to the bedside across all tumor types and treatment modalities. However, none of this advancement would be possible without the altruism of patients who are willing to selflessly participate on research protocols and in clinical trials for the betterment of others.

What is the biggest frustration as a doctor caring for CAR-T patients?

I believe my patients and I share a collective disdain for cancer when they are not able to achieve a response with CAR-T cells. While the treatment has a promising future in our armament against combating cancer, there are patients who either do not achieve a remission or exhibit disease relapses after achieving an initial response. The reasons for this aren’t always known; however may be secondary to the lack of CAR-T cell persistence; that is, the inability of CAR-T cells to maintain their presence for active cancer surveillance after the cancer has been eradicated or from “antigen escape” where the tumor deliberately loses the protein that the CAR-T cell was engineered to target. Nevertheless, learning from treatment failures is necessary and just as important as celebrating the success of those that are able to achieve favorable responses from this treatment.

 

We will soon publish Utty’s answer to my last three questions about his vantage point of caring for CAR-T patients in such an early stage of this potentially groundbreaking therapy’s development.