Addressing disparities in CAR T-Cell therapy trials : Oncology Times

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disparities

Chimeric antigen receptor (CAR) T cell therapy, a form of immunotherapy that uses genetically engineered T cells to recognize and destroy cancer cells, represents a new paradigm shift in the approach to cancer treatment. CAR T-cell treatment strategies are now available for certain leukemias, lymphomas and multiple myelomas.

However, minorities have been largely absent from the practice-changing clinical trials used to endorse and/or currently study these breakthrough CAR T therapies. Minorities often have tumor biology, immune system biology, and side effects that are distinct from non-minority individuals (Br J Cancer 2021; https://doi.org/10.1038/s41416-020-01038-6). Thus, this presents a challenge when attempting to generalize the findings, and efforts to address and remove these disparities will ensure the accessibility of this life-saving treatment strategy.

To better characterize outcomes in these underserved patient populations, a team from the National Cancer Institute-appointed Montefiore Einstein Cancer Center (MECC) compared the outcomes of ethnic minority patients versus non-minority groups with lymphoma. non-Hodgkin’s who received CAR T-cell therapy. The study was published in the journal A bone marrow transplant (2022; https://doi.org/10.1038/s41409-022-01670-1).

Investigators conducted an exploratory real-world retrospective cohort study evaluating 26 minority (17 Hispanic, 9 African American) and 20 non-minority (15 white, 5 Asian) patients who received CAR T-cell therapy between 2015 and 2021 in Montefiore. Male and female gender were evenly split in the minority group, while females predominated in the non-minority group (75%). The median age at the time of CAR T-cell therapy was 60.5 and 72 years, respectively.

The majority of patients in the minority group had a diagnosis of diffuse large B-cell lymphoma (DLBCL; 92%), while one patient had follicular lymphoma and one patient had mantle cell lymphoma (MCL). In the non-minority group, 85% had a diagnosis of DLBCL and 15% had a diagnosis of MCL. A total of 25 and 17 patients from the minority and non-minority groups, respectively, received treatment with axi-cel, while the remaining patients received brexucabtagene autoleucel.

Researchers found that among black and Hispanic patients who received CAR T-cell therapy, 58% achieved a complete response (CR), 19% a partial response (PR), and 23% experienced disease progression. sickness. For white and Asian patients, 70% achieved CR, 20% PR, and 10% disease progression.

In comparison to the Fisher’s exact test, no statistical differences between racial and ethnic origins were observed with regard to the response to CAR T-cell therapy and its tolerance. An analysis of progression-free survival did not reveal any differences between the groups (median not reached in the minority group vs. 11.9 months in the non-minority group), nor any difference in overall survival (46.3 months and not reached, respectively). Further analysis based on disease progression showed that the cumulative incidence of disease progression and death was similar in the two groups.

Additionally, the team assessed and compared the toxicities associated with CAR T-cell therapy between the two groups using the American Society for Transplantation and Cellular Therapy scoring system. Results were similar with respect to major side effects experienced: 96% and 95% of patients in the minority and non-minority groups with cytokine release syndrome, and 92% and 95% with effector cell-associated neurotoxicity syndrome immune grade 0-2, respectively.

Oncology time spoke with co-lead authors, Ira Braunschweig, MD, and Mendel Goldfinger, MD, for their perspectives on health disparities in clinical trials of CAR-T therapy. Braunschweig is Chief of the Section of Transplantation and Cellular Therapy at Rutgers Cancer Institute, Chief of the Transplantation and Cellular Therapy Department of the RWJBarnabas Health Oncology Service Line, and Director of Cellular Therapy and Bone Marrow Transplantation bone at Robert Wood Johnson University Hospital. Goldfinger is a medical oncologist at Montefiore Health System, an assistant professor of medicine at the Albert Einstein College of Medicine, and a member of the MECC Cancer Therapeutics Program.

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Ira Braunschweig, MD:

Ira Braunschweig, MD

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Mendel Goldfinger, MD:

Mendel Goldfinger, MD

Oncology time: Blacks and Hispanics have been largely absent from the major clinical trials that led to FDA approval of chimeric antigen receptor (CAR) T-cell therapies. What are some of the current barriers to minority representation in practice-changing CAR T therapy trials?

The golden finger: “It is an unfortunate but true fact that minorities were not well represented in any of the trials leading to CAR-T approval. I don’t think we fully understand what the barriers are, but we definitely need to look closely and do better to ensure that all people are represented in these trials.

Braunschweig: “I think the least talked about barrier is the fact that the sponsors of these studies – the pharmaceutical companies – often want to open their trials in centers that have the most well-known names and the most desirable zip codes, which which can lead to the exclusion of minority patients.. I give Kite a lot of credit for ‘going out on a limb’ and opening ZUMA-1 in Montefiore, a center in the Bronx that has a predominantly minority patient population.

Oncology time: What does this study mean for CAR T-cell therapies for these minority populations?

Goldfinger & Braunschweig: “This is the first published data we have to support these conclusions. It is very significant in that it shows that minorities who have the same access to care as their white counterparts will have the same outcomes as their counterparts. Furthermore, in the right hands, many of the challenges and social barriers these patients face that could potentially affect their outcomes can be overcome. More importantly, we hope this will encourage minority participation in these clinical trials. »

Oncology time: Only 8% of clinical trial participants are minorities nationally. What are possible solutions to increase racial and ethnic diversity in the clinical trial process?

Braunschweig: “I think there are far more qualified experts out there to answer this difficult and complex question. That said, one myth I would like to debunk is that people of color are reluctant to participate in clinical trials. I can’t think of any of our patients with relapsed and refractory lymphoma who have turned down a potentially life-saving therapy, either in-study or out-of-study with a relatively new FDA-approved treatment. Everyone wants a chance at survival.

The golden finger: “There has recently been talk of having a mandate for agents seeking FDA approval to have a minimum number of required minority representations. Other ideas have involved better outreach and education to minority communities and training investigators to consider some practical needs like access to care, ability to travel to centers that offer these tests and language barriers.

Oncology time: Going forward, what are the key questions that remain to be answered when it comes to continuing to fill the knowledge gaps about CAR-T therapy in these patient populations?

Braunschweig: “I think overall we’ve done a better job of elucidating the factors that make a practitioner consider a patient a CAR-T candidate or not. Once we understand this, it would be good to formally study these factors to see if they really affect the results or not. I think that would be particularly important for minority patients.

The golden finger: “Again, the best way to answer these questions is in a prospective clinical trial with a large minority population, so enrollment of minorities is absolutely essential. We need to know more about long-term outcomes and side effects. “We know that there is diversity in the immune systems of different populations and also in the biology of tumors. How these two factors affect outcomes needs to be examined in large cohorts of each ethnic population.”

Dibash Kumar Das is a contributing writer.

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