CAR T in Practice: What Oncologists Need to Know With Ehsan Malek, MD

Persistence, Resistance, and Translational Innovation

As Director of Translational Research for Multiple Myeloma at Roswell Park, Dr. Malek investigates novel chimeric antigen receptor (CAR) T-cell therapies and immunotherapies for multiple myeloma, bridging laboratory discoveries with phase 1 and 2 clinical trials. This vantage point gives him a comprehensive view of both the scientific evolution and real-world implementation of CAR T-cell therapy. Dr. Malek characterizes CAR T-cell therapy as very early in its development. “I would say CAR T cell is in the fetal phase,” he notes. “There’s lots to come.”

His research is centered on two key domains that will determine whether CAR T can fulfill its curative potential. The first is prolonging CAR T-cell persistence, as clinical outcomes depend in part on the type and fitness of T cells used. Roswell Park is working to engineer CARs that “persist and get activated more robustly to control the cancer.”

The second major focus is overcoming resistance imposed by the immunosuppressive tumor microenvironment. Efficacy is limited by the tumor’s ability to suppress immune responses, as the microenvironment of the tumor has tools that suppress the immune response as well as the CAR T-cell efficacy. To address this, Roswell Park is developing “armored CAR T cells that can survive the tumor’s immune shield.”

Practice-Changing Advances in CAR T-Cell and Immunotherapy

Immunotherapy is not new, Dr. Malek notes, tracing its origins back to allogeneic transplantation in the 1970s and 1980s. What has shifted dramatically in the last decade is precision, potency, and the ability to reduce reliance on cytotoxic chemotherapy.

CAR T-cell therapy represents a fundamental reconceptualization of cancer treatment. The approach involves harvesting a patient’s T cells, genetically modifying them to recognize tumor antigens, and reinfusing them. “We take these T cells that are somehow blind to cancer cells, genetically engineer them in a way that they can see cancer cells, and reinfuse them to patients. The cells expand and survive for a long time, and they keep fighting with the cancer,” often allowing patients to avoid ongoing chemotherapy. As Dr. Malek emphasizes, “CAR T cell is a very effective tool to bring a long remission without any further chemotherapy,” representing a shift from using chemotherapy as “essentially a poison to kill cancer cells” toward “enabling the immune system to fight with cancer.”

Beyond CAR T, two other immunotherapy platforms have reshaped the oncology landscape over the past decade. Checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) have transformed the management of several solid and hematologic malignancies. Since gaining traction in 2010, numerous agents have been FDA-approved for a variety of solid tumors, as well as hematologic malignancies such as Hodgkin lymphoma. Meanwhile, bispecific antibodies and T-cell engagers create a physical and functional bridge between native T cells and tumor cells. These agents “have two forks, one fork attached to native T cells and another fork attached to cancer cells, thereby enhancing the effectiveness of a patient’s immune system,” Dr. Malek explains. He views CAR T, checkpoint inhibitors, and bispecifics as three benchmark platforms that are still in a primary stage, with potential to cure subsets of hematologic malignancies as designs and combinations mature.

Survey Insights: Patients Increasingly Prefer CAR T

Roswell Park recently conducted a national survey to quantify public and patient awareness of CAR T-cell therapy and its perceived benefits. The team used an epidemiologic sampling strategy to capture different pockets of the social economy and create an accurate representation of the entire population. The results revealed striking enthusiasm for CAR T among individuals diagnosed with cancer. One in five patients, approximately 17%, prefer CAR T-cell therapy over traditional chemotherapy; 87% prefer either CAR T or chemotherapy; and only 4% prefer chemotherapy and not CAR T.

Dr. Malek describes this as a “very interesting finding that really proves that really CAR T-cell therapy is coming to the public stage,” reinforced by prominent media coverage including articles in The New York Times. Clinically, the survey’s implications are clear: even outside academic centers, patients are open to CAR T and ask questions about it, underscoring the need for all oncologists to be conversant with CAR T options and prepared to discuss them with patients.

Using Survey Insights to Guide Treatment Conversations

For practicing oncologists, especially in the community, the survey has direct implications for how they approach treatment discussions. Dr. Malek calls this “practice-changing knowledge,” noting that many patients are informed about CAR T and will ask about it even in settings where it isn’t offered locally. Closing the knowledge gap between patients and clinicians is essential, particularly because malignant hematology represents a small fraction of a general oncologist’s caseload. “Myeloma is 1% of all cancers, and for a general oncologist, it’s very important to be aware of this advancement in myeloma and lymphoma.”

The timing of referral to a CAR T center can significantly affect outcomes, making early consultation critical. With multiple prior lines of therapy, patients’ T cells become increasingly exhausted. Prolonged exposure to bispecifics or T-cell engagers can further degrade T-cell fitness. “If you have long exposure to T-cell engagers or bispecifics, the T cells’ quality is not as good as before that, and the therapy becomes less effective,” Dr. Malek warns. He advises that community oncologists should have a “very low threshold to reach out to academic centers to refer their patients,” emphasizing that “early consultation is very important.”

Perhaps most importantly, Dr. Malek argues that oncologists need to reframe treatment discussions around value and quality of life rather than traditional metrics alone. “I think we are moving toward framing conversations around value rather than just prolonged remissions or prolonged survival,” he states. In his experience, “more often than you’d expect, patients care more about quality of life than about how long they live.” The treatment-free period that CAR T may provide—allowing patients to avoid weekly chemotherapy—represents enormous value. Even if chemotherapy were hypothetically free of toxicity, “just the concept of going every week to get cancer therapy is a mental barrier.” He argues that “the value that CAR T brings to patients rather than continuous therapy” supports reframing oncologic decisions “around value rather than metrics such as survivals and remissions.”

Expanding and Equalizing Access: Community, Academic Centers, and Payers

Despite growing enthusiasm, access and equity remain central challenges for CAR T deployment. For myeloma and lymphoma, Dr. Malek notes that approximately 70% of patients across the country are not being treated in academic centers that offer CAR T.” Community oncologists are “the first line of the fight,” making their education and engagement crucial for expanding access. “Empowering those providers with knowledge, making sure that early consultation happens, and framing the treatment strategy around CAR T rather than continuous therapy, I think, is key,” he emphasizes.

Academic centers also have a responsibility to decentralize CAR T delivery through regional hub-and-spoke models. Roswell Park is implementing such a strategy, educating their referral base to send patients early, performing CAR T at Roswell, and then returning patients two weeks after infusion to the primary oncologist. Protocols and follow-up instructions are shared so that patients don’t have to stay in Buffalo for an extended period of time. Dr. Malek believes this model should be mirrored nationally. “Among all centers around the country that offer CAR T cell, decentralization is a theme that is very important for expanding access,” he states.

The third piece of the access puzzle involves payers and health financing. Fee-for-service structures built around recurrent chemotherapy infusions are fundamentally misaligned with one-time treatments. Dr. Malek advocates evaluating therapies “based on a patient’s value rather than the benchmark that is fee-based.” He frames this as a “triple player” challenge involving community oncologists, academic centers, and payers working together to reduce disparities and expand equitable access.

Future Directions

Looking ahead, Dr. Malek highlights three areas where innovation could significantly reshape standards of care over the next decade. The first is allogeneic or off-the-shelf CAR T-cell therapy. Manufacturing is “one of the main bottlenecks in CAR T-cell,” with current autologous products requiring six to eight weeks of individualized production using patient T cells. This process is tedious, time-consuming, and as expensive, as it requires individual production for each patient.

Allogeneic CAR T, derived from healthy donors, could be manufactured in massive amounts and off the shelf, available at multiple centers without long wait times. Crucially, these cells come from healthy individuals rather than patients whose T cells are already impacted by prior chemotherapy. Host rejection of donor T cells is a challenge, but Dr. Malek notes efforts to address this, including CRISPR-based editing of relevant receptors. ” So far, we have a very good solution to address rejection, so stay tuned. I think the future of allogeneic CAR T cell is very bright.” He anticipates that allogeneic products will significantly lower costs and help address current access gaps and disparities.

The second major innovation involves armored CAR T cells designed to defeat the tumor immune shield. To increase efficacy while keeping toxicity manageable, Roswell is pioneering an armored approach in which CAR T cells can penetrate the microenvironment’s shield. The armoring strategy involves inserting cytokine genes and modulating pathways such as TGF-β so that CAR T cells can function more effectively within the hostile tumor microenvironment.

The third frontier involves rational combination strategies with bispecifics and T-cell engagers to deepen responses and potentially achieve cure in subsets of patients. Roswell is testing CAR T followed by bispecifics targeting a different antigen in myeloma, with the goal of eradicating residual disease. Dr. Malek observes that the overall response rates with CAR T and bispecifics as single agents are “unheard of in the history of myeloma. If we combine these two, we may even be able to cure a subset of patients.”

For his patients with myeloma, Dr. Malek’s advice is hopeful but grounded in the reality of ongoing innovation. “I encourage them not to give up. There are lots of innovations coming to horizon which may enable us to cure the disease.”

Key Takeaways

• CAR T-cell therapy is early but transformative. Despite being in a “fetal phase,” CAR T is already reshaping expectations for remission depth and chemotherapy-free intervals in hematologic malignancies. Early referral is essential, as T-cell exhaustion from multiple prior lines and bispecific exposure can compromise quality and outcomes. Clinicians should maintain a low threshold for early referral to CAR T centers.
• Patients increasingly expect CAR T to be discussed. National survey data show a strong preference for CAR T among patients with cancer, and clinicians should be prepared for informed questions, even in non-academic settings. Value and quality of life should be central in treatment discussions, as many patients prioritize treatment-free periods and relief from the cognitive and psychological burden of ongoing chemotherapy. Oncologists should frame CAR T in terms of value, not just survival metrics.
• Access requires coordinated system-level change. Hub-and-spoke models, education of community oncologists, and payer reform are crucial to decentralize CAR T delivery and reduce disparities. Future innovations may reduce costs and improve cure rates, as allogeneic off-the-shelf products, armored CAR T designs, and strategic combinations with bispecifics and T-cell engagers are poised to advance efficacy, safety, and access over the next decade.

About Dr. Malek

Ehsan Malek, MD, is an Associate Professor of Oncology and the Director of Translational Research for Multiple Myeloma at Roswell Park Comprehensive Cancer Center. He specializes in the treatment of patients with plasma cell disorders, including multiple myeloma, MGUS, and amyloidosis. He leads Roswell Park’s translational research investigating novel cellular and immune-based therapeutic strategies for multiple myeloma, and he is passionate about developing new approaches to improving patients’ quality of life and outcomes.