When we train physicians on CAR-T cell therapy, much of the discussion centers on toxicity management. Cytokine release syndrome (CRS), an exaggerated immune response that may present with high fevers, hypotension, hypoxia, and organ dysfunction, remains the most recognized complication, alongside immune effector cell–associated neurotoxicity syndrome (ICANS), which can manifest as confusion, aphasia, tremors, or seizures. Both span a wide spectrum, from mild and self-limited to life-threatening, and patients may also develop prolonged cytopenias, severe infections, hypogammaglobulinemia, and secondary malignancies. These risks are real, and oncologists must understand the full spectrum of acute and long-term toxicities.

Even so, I would argue that our emphasis is misplaced. The greatest threat to many CAR-T candidates is not a complication we can manage within the hospital. It is the appointment they never make, the referral that comes too late, or the patient who qualifies on paper but never reaches infusion. While we refine toxicity grading and supportive care, many eligible patients are lost earlier, through delayed referral, socioeconomic barriers, geographic inequities, or prolonged authorization. For these patients, the determinant of outcome is not whether they develop grade 1 or grade 3 CRS, but whether they gain access to therapy at all. Improving access may ultimately save more lives than any incremental gain in toxicity management.

The numbers bear this out. In a 2025 analysis from a large academic center, Valtis and colleagues found that 44% of referred patients never received CAR-T, consistent with prior reports of one-third to one-half. Among those referred but never infused at one center, disease progression was the most common cause of death, roughly 64%. The science of cellular therapy is breathtaking, but none of it matters if the patient in front of us cannot reach the treatment in time.

The Clock That Actually Predicts Survival

The CAR-T timing number most often discussed is “vein-to-vein” time, the interval between collecting a patient’s T-cells and reinfusing them after re-engineering. Controlled largely by manufacturing, it runs a median of roughly 30 to 50 days across commercial products. The clock that gets less attention, and matters more, is what I call brain-to-vein time: from the moment a clinician decides a patient needs CAR-T through referral, evaluation, insurance authorization, and scheduling for cell collection. That adds another 30 to 40 days. Combined, a patient can wait close to 100 days from decision to infusion.

That delay has consequences. In a 2024 analysis by Jallouk and colleagues, delayed axi-cel infusion wa associated with a median overall survival of 7.8 months, versus 26.4 months for on-time infusion, a difference of nearly 19 months. For a patient whose disease is progressing quickly, 100 days can be the difference between a treatment aimed at cure and one aimed at comfort, and the delay falls hardest on patients in rural areas, on Medicaid, or without a caregiver.

Same Disease but Different Zip Codes: James Lived. Maria Did Not.

Consider two patients with diffuse large B-cell lymphoma, the most common aggressive lymphoma. Same molecular markers, essentially identical lab values at relapse. On paper, the same disease.

James has commercial insurance and lives 20 miles from the CAR-T center in Houston. His wife can serve as a full-time caregiver. The day he relapses, his oncologist refers him; authorization takes about two weeks; he is infused 28 days after referral. Fifteen months later, he is alive. Maria is on Medicaid and lives 130 miles from the nearest center. Her husband works full time, she cares for her mother-in-law, and she cannot afford the repeated drive. She is placed on bridging chemotherapy while referral and authorization proceed. By the time she is infused, 66 days have passed. Her disease progresses during the wait; she develops severe CRS and ICANS, loses her job, achieves only a partial response, and dies.

The difference mirrors population-level data. In a 2025 Northwestern real-world analysis, patients referred but never infused had a median overall survival of 2.5 months from relapse, versus 45.9 months for those infused, a gap of roughly 30 months measured from the treatment time point. This is not a story about two unusual patients. It is a pattern.

What Decides Who Gets Treated

Distance. Chung and colleagues (2025) estimated that if patients in “poor access” states (averaging 104 miles from a treatment center) lived the 34-mile average of “better access” states, roughly 38% more would receive CAR-T. Ahmed and colleagues (2024) found that two-to-four-hour drive times significantly reduced the likelihood of treatment. In Oregon, where OHSU is the only academic cancer center and the next nearest is almost 200 miles away, geography decides who is treated. CAR-T remains concentrated at a small number of academic centers in major metropolitan areas.

Insurance. Medicaid approval can take four to six weeks of medical-necessity documentation and appeals, versus one to two weeks for commercial insurance. In some states Medicaid will not cover care across state lines, so an insured patient can still be locked out when the nearest center is in the next state.

Race and ethnicity. Black and Hispanic patients are referred less often and receive therapy at only about 67% and 72% of expected rates. In the Valtis analysis, Black race carried 70% lower odds of completing therapy after referral, and among pediatric patients whose cells were already collected, 36.4% of Black children did not receive infusion versus 5.8% of others. This is not biology. It reflects referral patterns, language and financial barriers, and a system that has historically underserved these communities.

Poverty and age. Patients in the lowest income group are more than twice as unlikely to receive CAR-T as the highest, and higher social vulnerability carries 16% to 30% lower odds of completing therapy. Age compounds this: up to 80% of eligible older adults with relapsed or refractory DLBCL never receive CAR-T, and only about 13% of Medicare recipients are 75 or older, though the oldest patients in the largest published series were 89, with outcomes not meaningfully worse. Lack of a caregiver, who must monitor the patient for weeks after infusion, is the single most common reason patients cannot proceed, and it falls disproportionately on women.

Other health conditions. Real-world patients do not look like trial participants. Patients on dialysis and those with liver enzymes three times the upper limit of normal have safely received CAR-T. A coexisting condition should prompt a call to the CAR-T center, not an automatic decision to withhold referral.

What Community Oncologists Can Do Right Now

The single most impactful step is to refer earlier and faster. For multiple myeloma, every patient will eventually be a candidate for cellular therapy, so refer at diagnosis or first relapse rather than waiting for later lines. For aggressive lymphomas, high-risk patients are usually identifiable by the second or third cycle of first-line therapy; refer the moment clinical suspicion is high. The eligibility clock starts at referral, not infusion.

Establish a streamlined referral pathway so workup, authorization, and scheduling proceed in parallel rather than sequentially.
Start insurance authorization early, before bridging chemotherapy is complete.
Return patients to community care as soon as it is safe; the month-long hospitalization model is giving way to earlier return.
Educate patients about CAR-T early, before they are in crisis, so the decision is not their first exposure to the concept.

CAR-T Is Moving Closer to Where Patients Live

CAR-T as an inpatient, academic-center-only therapy is changing. The first published experience of outpatient CAR-T in a community oncology practice independent of academic affiliation (Simmons and colleagues, 2026) treated 41 patients with remission rates consistent with published data and no unexpected safety concerns under home monitoring. The first prospective trial of outpatient axi-cel (Dholaria and colleagues, 2025) confirmed feasibility with no grade 3 or higher CRS and no treatment-related deaths. Success depends on careful patient selection, robust remote monitoring, clear escalation pathways, and local partners, intensivists, neurologists, and infectious disease specialists, available around the clock. Hub-and-spoke models and evolving case-rate reimbursement point the same direction, though community apheresis capacity remains a bottleneck. None of these models is perfect, but each moves CAR-T closer to the patients who need it.

Clinical Implications and Practice Takeaways

Brain-to-vein time is a survival variable. Delays fall hardest on patients with Medicaid, those in rural areas, patients of color, and those without a caregiver.
Refer earlier than feels necessary. Myeloma at diagnosis or first relapse; aggressive lymphoma when suspicion is high, not after the next scan.
A coexisting condition is a conversation, not a barrier. Call the CAR-T center before ruling a patient out.
Work with your regional center on workflow, and advocate aggressively with insurers, since many Medicaid approvals require appeal.
Build outpatient and community infrastructure now, before the first patient needs it.

Patient Perspective: What This Means for You

If your oncologist has mentioned CAR-T, or if you have a blood cancer such as lymphoma or myeloma that often requires multiple treatments, ask about a referral early rather than later. The sooner you are evaluated at a CAR-T center, the more options you will have. If distance, insurance, or caregiving are concerns, tell your care team; resources exist to help, including social workers, nurse navigators, and financial assistance programs, but only if you are in the system early enough to use them.

Key Takeaways

Roughly 44% of referred patients never receive CAR-T; among those referred but not infused at one center, progression caused about 64% of deaths.
Brain-to-vein time adds 30 to 40 days to the manufacturing timeline; a patient can wait close to 100 days, and delay is associated with markedly worse survival.
Distance, poverty, insurance type, age, and lack of a caregiver each independently reduce the likelihood of receiving CAR-T, and fall hardest on Medicaid, rural, and minority patients.
CAR-T remains concentrated at academic centers in major metros, and some Medicaid plans will not cover out-of-state care.
The highest-impact step today is to refer earlier and faster, and to build the workflows that bring CAR-T closer to where patients live.

References and Resources

Valtis YK, Chin KK, Nemirovsky D, et al. Barriers to Chimeric Antigen Receptor T-Cell Therapy. JAMA Oncology, 2025.
Jallouk AP, et al. Impact of delayed infusion on outcomes in patients treated with axicabtagene ciloleucel. Haematologica, 2024.
Northwestern University real-world analysis of referred but non-infused CAR-T patients. Journal of Clinical Oncology 43 (2025), suppl 16, abstr 7056 (ASCO Annual Meeting).
Locke FL, Siddiqi T, Jacobson CA, et al. Impact of Vein-to-Vein Time in Patients With R/R LBCL Treated With Axicabtagene Ciloleucel. Blood Advances, 2025.
Chung A, Shafrin J, Vadgama S, et al. Inequalities in CAR T-Cell Therapy Access for US Patients With Relapsed/Refractory DLBCL: A SEER-Medicare Data Analysis. Blood Advances, 2025.
Ahmed N, Sun F, Teigland C, et al. CAR T-Cell Access in Relapsed/Refractory Large B-Cell Lymphoma: Association With Social Determinants of Health and Travel Time. Transplantation and Cellular Therapy, 2024.
Boloori A, Nategh E, Su CT. Association of Social Vulnerability Index and CAR T-Cell Therapy Administration, 2018–2023. The Oncologist, 2025.
Chihara D, Liao L, Tkacz J, et al. Real-World Experience of CAR T-Cell Therapy in Older Patients With Relapsed/Refractory DLBCL. Blood, 2023.
Tun AM, Patel RD, St-Pierre F, et al. Anti-CD19 CAR T-Cell Therapy in Older Patients With Relapsed or Refractory Large B-Cell Lymphoma: A Multicenter Study. American Journal of Hematology, 2024.
Simmons GL, Cross S, Pittos EC. Advancing Access to CAR T-Cell Therapy: Real-World Experience From a Community Oncology Practice. Frontiers in Oncology, 2026.
Dholaria B, Bhaskar ST, Patel VG, et al. Feasibility of Axicabtagene Ciloleucel in the Outpatient Setting: Primary Analysis of a Prospective Trial. Bone Marrow Transplantation, 2025.
Alqazaqi R, Schinke C, Thanendrarajan S, et al. Geographic and Racial Disparities in Access to CAR-T and Bispecific Antibody Trials for Multiple Myeloma. JAMA Network Open, 2022.
National Comprehensive Cancer Network (NCCN). B-Cell Lymphomas and Multiple Myeloma Guidelines. Available at: nccn.org.

About the Author

Dr. Carolina Escobar is a hematologist-oncologist specializing in stem cell transplantation and cellular therapy at the Baylor University Center in Dallas, Texas, where she is recognized as a leading specialist in her field. She serves as a professor of hematology and oncology for students at Baylor University and Texas A&M, and has served as director of apheresis and assistant director of the stem cell transplant and cellular therapy program.

She is a co-founder of the Vitruvio Institute of Medical Advancement (VIMA), a nonprofit focused on integrating new technologies into clinical practice, where she helped implement telemedicine programs for medical teams and refugees in Kurdistan, for US Oncology, and for the transplant service at Texas Oncology. She has contributed to publications advancing the fields of cellular therapy and lymphoma treatment. Dr. Escobar is also the founder of Fundación Huellas Sanadoras, a nonprofit that improves the psychosocial and physical wellbeing of vulnerable populations through animal-assisted interventions in hospitals and clinics across Colombia and Latin America.