Shots:
- In a retrospective study sourced from EHR data for DLBCL patients, groundbreaking insights were unearthed that could potentially shape the treatment landscape of CAR-T Therapies in DLBCL
- Data from the 10-year study is divided into pre- and post-CAR-T eras to better reflect trends in patient demographics and disease progression
- PharmaShots welcomes Dr. Ira Zackon, Senior Medical Director, Ontada, in an illuminating conversation.
Saurabh: Welcome to PharmaShot’s Viewpoint! How do the trends appear during the pre- and post-CAR-T approvals in the US?
Ira: For DLBCL, the CAR-T era began with the first FDA approval in October 2017 for the treatment of relapsed disease. Our retrospective study, sourced from EHR data in the community oncology setting, studied the bigger picture look at the patient characteristics and survival in DLBCL patients, from October 2014 to October 2023. We then looked at this data in the group prior to and post October 2017 (the pre and post CAR-T era for this disease), allowing for 3 years of data capture in each group. We did not see any significant trends of differences in either the overall patient demographics and stage of disease or in the 1 and 2 years survival proportions after their diagnosis.
Saurabh: Please shed some light on the noteworthy analyses from the study.
Ira: This was a really high-level overview description of patients and survival. There were more DLBCL patients in the post CAR-T era. While there is an increased incidence of DLBCL compared to the past, this also likely more reflects growth of the practices in the network utilizing our EHR data base. There was no notable difference in patient age, sex, race/ethnicity or stage of disease. Finally, at least at this high overall population level, there was no difference in short term 1 and 2 year survival outcomes. Most patients with DLBCL will relapse within 1-2 years of treatment and we have learned of the curative potential of CAR-T therapy. We did not at least see any difference, although the short-term survival variable may remain too short. We also should note that the post CAR-T era did include the COVID19 pandemic, although we cannot infer its impact from this data. Hypothetically, it could have increased mortality in this population through direct consequences of COVID infection or delay in DLBCL diagnoses and treatment. The next phase of real-world research on the impact of CAR-T, will need more follow up time and also get at more granular details on the DLBCL disease subsets, evolving patterns of care for relapsed DLBCL and more detailed safety and efficacy analyses.
Saurabh: Though the results showcase no significant deviation in patient characteristics, there was, however, an increase in non-white participation in the study. Please elaborate on this.
Ira: First there was no difference in the proportion of White or Black patients. Black Americans in our data represented about a third of their proportion of the general population. However, there does appear to be a lower incidence of DLBCL in Blacks. We did see an increased proportion of other Race/Ethnicities in the post CAR-T population and this likely reflects demographic changes in the practice geographic regions.
Saurabh: From the study results, we can infer fewer adoption of CAR-T therapy in real-world settings among DLBCL patients. What are the key reasons for the lack in adoption on CAR-Ts or Cell and Gene Therapy?
Ira: I agree it is likely that a low adoption of CAR-T therapy in real world setting of DLBCL patients may contribute to a lack of observed difference in outcomes in the post CAR-T era in our data set. There are several potential barriers to getting to CAR-T. First, the real-world population is more heterogeneous than those that go on clinical trials and more patients may not be optimal candidates for CAR-T. Second, CAR-T therapy is an intensive experience in which patients may need to travel a distance to a CAR-T program center, be away from home for perhaps a month and needs to have caregiver support. Third, there have been times of limitations on production of CAR-T cells or limited capacity of CAR-T centers that could lead to delays in patients getting to CAR-T, in which their disease may not stay under control. Fourth, at least in the earlier time post CAR-T approval, payers needed to establish their contractual policies on very expensive therapy and care needs. And there are natural lags in the uptake of new, and especially complex, therapies. A combination of these may have contributed to not observing any impact in our data in the post CAR-T era, although again the 1 and 2 year from diagnosis survival metric may be too short still, especially as other therapies for relapsed DLBCL have become available to improve these outcomes as well.
Saurabh: What are your views on how likely are the adoption patterns to change (negative or positive) with new approvals and why do you think so?
Ira: CAR-T therapy, with further maturation of the clinical trial data, is clearly showing the potential for durable remissions and cure in relapsed DLBCL. This is not true of other available therapies for those patients not eligible for autologous stem cell transplantation therapy. The bispecific antibodies are clearly effective and another exciting way to also direct T cell immune therapy to treat DLBCL, with lower level of risk and toxicity and easier to administer in the community setting. There are some challenges to standing up safe delivery of bipsecifics in the community setting but this will likely rapidly improve and is necessary to make this more broadly accessible for our patients. However, we do not yet have more mature follow up on the data to know how durable these responses and remissions will prove. We may well see increased use of CAR-T for eligible patients, especially if we can help facilitate overcoming any logistical limitations for patients to get to CAR-T. Furthermore, toxicity of CAR-T is likely to reduce going forward with improved CAR-T products of the future and ways to prevent the incidence and severity of CRS and neurotoxicity events and hopefully be able to have future CAR-T completely in the outpatient setting in the future. Then we will see where things go with longer term results of bispecific antibody therapies.
Saurabh: As you said high cost of treatment is one of the reasons for lack in the adoption of CAR-T. Do you think are there any companies who are working to bring down the CoT for CAR-Ts or Cell and gene therapy?
Ira: We always hope costs may come down with more competition of CAR-T products, but these therapies are inherently costly to produce and deliver. There has been some exploration of novel contracting, in pay for successful outcomes formulae but I am not aware of any such paradigms coming into use. At the same time, if CAR-T therapy can lead to durable long-term remissions, maybe in earlier lines of therapy even, then the upfront cost could still be valuable in eliminating the downstream costs of relapsed DLBCL in terms of total cost of care over time. It is possible that newer products could have lower cost of production that could reflect in lower prices of the products and if we are able to reduce the incidence and severity of CRS, we may be able to reduce or eliminate the hospitalization needs, which also are significant costs to the total cost of care. There are also CAR-T products in development that are not requiring the T cells from the patients, but engineered from donor T lymphocytes (allogeneic) that then can be more available “off the shelf” CAR-T products. So hopefully, one way or the other or through a combination of these, we will see improved access, lower risk and cost to this therapy.
About the Author:
Dr. Ira Zackon
Dr. Ira Zackon is a recently retired Hematologist/Oncologist and past President of New York Oncology Hematology in The US Oncology Network. He currently serves as a Senior Medical Director with Ontada, focused on Real World Data and Research.
Dr. Zackon received his medical degree from McGill University, Montreal, Quebec, Canada, followed by a residency in Internal Medicine at the Royal Victoria Hospital, McGill University, Montreal and fellowship in Hematology/Oncology at Dartmouth-Hitchcock Medical Center.
Related Post: Standardizing DLBCL Treatment: Dr. John Burke in a Riveting Conversation with PharmaShots
