Innovations in CAR T Across Adult and Pediatric Practice: Perspectives from Dr. Michael D. Jain and Dr. Stephen Gottschalk

Thursday, February 19, 2026

A recent ASTCT webinar held on December 2, 2025 discussed innovations in CAR T for adult and pediatric patients, highlighting how CAR T-cell therapy is maturing into a therapy defined not only by response rates, but by execution: selecting the right patient at the right moment, managing predictable inflammatory toxicities with confidence, and building durable survivorship pathways. Dr. Michael D. Jain (Moffitt Cancer Center) framed the adult experience through a pragmatic lens, emphasizing that real-world outcomes in lymphoma and myeloma are increasingly consistent with pivotal trial expectations, while care models continue to evolve as programs become more experienced and CAR T moves earlier in the relapsed or refractory setting.

Dr. Stephen Gottschalk (St. Jude Children’s Research Hospital) offered the pediatric perspective, where CAR T has fundamentally changed the outlook for relapsed or refractory B-cell malignancies, yet durability remains the central challenge. His talk focused on why relapse still occurs, what engineering strategies may prevent it, and why diseases like AML and solid tumors demand a different level of biologic control. Together, the talks provided a cohesive view of CAR T as both a current standard and an active frontier.

For a visual summary of the discussion, view the innovations in CAR T infographics here.

Innovations in CAR T for Adult Patients

Michael D. Jain, MD, PhD, Moffitt Cancer Center

Overall, Dr. Jain’s talk connected how CAR T cells behave in patients with what that means at the bedside. He highlighted why CRS and ICANS have become more predictable with earlier, protocol-driven intervention, and why longer-term vulnerabilities, especially infection risk during immune recovery, now drive much of the post–CAR T burden. He also pointed to newer, less typical toxicities that programs need to recognize promptly and described practical approaches to improving outcomes as CAR T use expands into diseases such as CLL.

CAR T in the real world: efficacy is durable, and use is moving earlier

A key framing point was that adult “real-world” CAR T experience in lymphoma and multiple myeloma has largely matched the efficacy and safety signals seen in landmark studies, which has strengthened clinician confidence and expanded referral. As durable responses have become more predictable, many centers are increasingly considering CAR T earlier in the relapsed or refractory course, when patients can arrive with better performance status, lower inflammatory risk, and more favorable disease biology.

At the same time, Dr. Jain emphasized the operational reality that vein-to-vein time can stretch for weeks, and that many patients need bridging therapy to maintain disease control during manufacturing. This interval is not a neutral waiting period. It can determine whether a patient reaches infusion with manageable tumor burden or with accelerating disease that increases both toxicity risk and the chance of suboptimal response.

Hyperinflammatory syndromes after CAR T: pattern recognition over single thresholds

Dr. Jain emphasized that multiple hyperinflammatory syndromes can occur after CAR T and that they cannot be differentiated by a single lab value alone. The most useful clinical tools are timing, symptom pattern, trajectory, and response to therapy.

He described the familiar sequence in which:

CRS typically occurs early as systemic inflammation that tracks CAR T expansion

ICANS often overlaps with or follows CRS, presenting as neurologic toxicity and encephalopathy

These toxicities are increasingly predictable and manageable with standardized monitoring and early intervention, and practice has shifted toward treating sooner rather than waiting for advanced severity. He highlighted how the field has moved from hesitation about immunosuppression to a more proactive approach when inflammatory signals begin to rise, with the goal of preventing progression to severe toxicity.

He also described HLH-like or hyperinflammatory syndromes as scenarios where inflammation persists or escalates despite standard CRS-directed management. In these cases, clinicians must broaden the differential to include infection and disease progression while considering additional immunomodulatory strategies. The central point was that differentiation depends on clinical context and timing relative to infusion, not a fixed ferritin cut-off or a single marker.

Survivorship is now a defining part of CAR T care

A major theme was that long-term outcomes are increasingly shaped by complications beyond CRS and ICANS. Dr. Jain highlighted infections as a leading driver of late morbidity and mortality in adults after CAR T, particularly in patients with prolonged cytopenias and hypogammaglobulinemia. This shifts the center of gravity of CAR T supportive care toward prevention and immune recovery planning.

Infection prevention was framed as a core program responsibility, including:

antimicrobial prophylaxis strategies

vaccination approaches timed to immune reconstitution

immunoglobulin replacement when clinically indicated

He also discussed how survivorship needs broaden beyond infection alone, drawing on transplant-style models for chronic cytopenias, secondary malignancy surveillance, and multidisciplinary long-term follow-up.

Access and care models: outpatient CAR T is feasible, but not automatic

Dr. Jain emphasized that access to CAR T remains uneven and influenced by referral patterns, payer and logistical barriers, and center experience. As programs mature, outpatient CAR T has become feasible and safe for carefully selected adult patients, but it requires experienced teams and rapid escalation pathways to inpatient care.

He highlighted that successful outpatient delivery depends on a coordinated multidisciplinary infrastructure, typically involving physicians, advanced practice providers, nursing, pharmacy, and care coordination, with standardized protocols and reliable patient monitoring.

Optimizing CAR T in CLL: depth of response is the goal

In CLL, Dr. Jain framed commercial CAR T as an important advance, but one where the ceiling remains defined by complete response rates and durability. He emphasized that long-lived, “cure-like” remissions correlate most strongly with deep response, and that barriers to CR include high disease burden and impaired T-cell fitness in CLL.

He discussed strategies used to optimize outcomes in practice, including maintaining disease control through the CAR T process, improving the quality of collected T cells, and using MRD monitoring to guide post-CAR T planning. The broader message was that CLL may require more deliberate “therapy orchestration” around CAR T than many B-cell lymphomas.

Selected takeaways

Acute toxicities are increasingly predictable, and earlier intervention has become common practice.

Hyperinflammatory syndromes require timing and pattern-based differentiation, not single lab thresholds.

Long-term infection risk is central to adult CAR T outcomes, and prevention must be built into survivorship care.

Manufacturing timelines, bridging therapy, and access barriers remain major determinants of who benefits from CAR T.

Innovations in CAR T for Pediatric Patients

Stephen Gottschalk, MD, Department of Bone Marrow Transplantation & Cellular Immuno-Oncology, St. Jude Children’s Research Hospital

Dr. Gottschalk’s talk traced where pediatric CAR T has delivered clear benefit and where fundamental barriers still limit durability. He contrasted the high remission rates achieved in B-ALL with the ongoing challenge of maintaining long-term disease control, then discussed how CAR T for T-cell malignancies is constrained by lineage targeting and the risks that come with it. He framed AML, as well as solid and brain tumors as harder biologic problems, shaped by target selection and suppressive microenvironments, and emphasized that meaningful progress will require multi-antigen strategies and smarter engineering rather than simply applying leukemia-era designs to new diseases.

Pediatric B-ALL: remission is common, durability remains the central challenge

Dr. Gottschalk emphasized that pediatric CD19 CAR T has been a transformative success in inducing remission, with CR rates often exceeding 80% across products, yet long-term survival remains substantially lower. He framed this gap as the core pediatric problem: achieving remission is no longer the main hurdle, sustaining it is.

He outlined established risk factors associated with failure or relapse, including prior CD19-directed therapies, high disease burden, and unfavorable cytogenetics. He also highlighted that pediatric implementation raises dosing and pharmacokinetic considerations, particularly around lymphodepletion, since younger children can metabolize agents like fludarabine differently than adults. Across pediatric ALL, depth of remission is especially important, and deep MRD negativity is closely linked to durable benefit.

Post-remission management was presented as an active decision point. Pediatric teams monitor MRD and immune recovery and must decide whether observation is appropriate or whether a planned consolidative allogeneic transplant is needed. These decisions incorporate comorbidities, caregiver preferences, disease features, prior transplant history, and the expected persistence profile of the CAR product.

Why relapse happens: antigen escape and limited persistence

Dr. Gottschalk organized relapse biology into two dominant mechanisms:

Antigen escape, such as CD19 downregulation

Limited persistence, where CAR activity does not last long enough to maintain control

He reviewed strategies to mitigate antigen escape, especially dual targeting of CD19 and CD22, using approaches such as co-administration of CAR products, dual CAR expression, or bispecific CAR designs. Importantly, he emphasized that these solutions are not fully “solved,” because dual targeting can introduce tradeoffs like accelerated exhaustion or uneven binding-domain function, which can undermine persistence and efficacy.

To improve persistence, he discussed both combination approaches and intrinsic engineering strategies. He emphasized that simply adding checkpoint blockade has not consistently boosted CD19 CAR performance in pediatric ALL, which pushes the field toward better product design and additional genetic engineering beyond target specificity. He highlighted next-generation approaches that aim to tune activation and enhance durability through deeper control of T-cell state.

Pediatric T-ALL/LBL: fratricide, contamination risk, and lineage depletion

For T-ALL/LBL, Dr. Gottschalk described the promise of targeting lineage antigens such as CD5 and CD7, but emphasized the unique challenge of fratricide because these targets can be expressed on the therapeutic T cells themselves. He reviewed strategies to avoid fratricide, including antigen deletion via gene editing, intracellular retention approaches, manufacturing selection effects, and use of pharmacologic inhibitors such as dasatinib during production.

Even with encouraging efficacy signals, he emphasized two major concerns: the risk of contaminating autologous products with malignant T-cell blasts, and the potential for profound T-cell depletion due to on-target effects. These challenges strengthen the rationale for allogeneic approaches and for controllable platforms that can be switched off or depleted after a deep remission is achieved.

AML and solid tumors: the same hard problems show up in different forms

Dr. Gottschalk framed AML as facing an “antigen dilemma,” where many candidate targets are shared with normal hematopoietic stem cells or essential myeloid populations. He highlighted emerging targets with more restricted normal expression, which may improve the therapeutic window, but emphasized a second major barrier: an immunosuppressive microenvironment that resembles solid tumor biology and can blunt CAR function.

He described a paradox seen in many AML CAR studies: high rates of inflammatory toxicity can occur without translating into strong anti-leukemic activity, underscoring that inflammation is not the same as effective tumor killing. He also emphasized the importance of field coordination, including harmonizing trial reporting and correlative science so the community can learn faster from small early-phase experiences.

In solid tumors and brain tumors, he noted that safety has been demonstrated across many targets and platforms, with examples of long-term survivors, but broad efficacy has remained limited. He highlighted that signals can improve in the right clinical context, particularly lower disease burden scenarios, and that engineered “armored” strategies that augment cytokine signaling may help overcome microenvironmental suppression.

Pediatric care delivery and survivorship: families are part of the therapeutic system

Dr. Gottschalk emphasized that pediatric CAR T differs from adult CAR T not only biologically but operationally. Immune reconstitution patterns and long-term survivorship priorities include growth and developmental outcomes, which require structured long-term follow-up. Infection risk remains central, especially in heavily pretreated children and in those with prolonged B-cell aplasia, making immunoglobulin replacement and prevention strategies essential.

Outpatient pediatric CAR T can be feasible in selected patients, but it depends on intensive caregiver education, age-appropriate neurologic assessment, and clear pathways for rapid escalation to inpatient care. Families play a critical role in early symptom recognition and adherence to monitoring.

Selected takeaways

Pediatric B-ALL CAR T achieves high remission rates, but durability depends on deep remission and persistence, and relapse biology remains the key challenge.

Dual targeting can reduce antigen escape risk, but it introduces engineering tradeoffs that still need to be solved reliably.

T-ALL/LBL raises unique risks from lineage targeting, including fratricide and clinically meaningful T-cell depletion.

AML and solid tumors share core obstacles: antigen selection and microenvironment suppression, requiring multi-antigen strategies and deeper engineering.

What These Two Talks Reveal About the Next Phase of CAR T

Taken together, these presentations show a field that is simultaneously standardizing and reinventing itself. In adults, CAR T has become more operationally confident: toxicity timing is better understood, earlier intervention is common, outpatient models are increasingly viable, and long-term outcomes are now shaped heavily by infection prevention and survivorship infrastructure. In pediatrics, CAR T is a true breakthrough for B-cell malignancies, but the next gains depend on outsmarting relapse mechanisms and building products that persist, resist exhaustion, and function in difficult microenvironments.

The shared message is that the next generation of CAR T progress will come from aligning biology with care systems. Tumor burden, immune context, manufacturing timelines, and multidisciplinary follow-up increasingly determine whether the promise of CAR T becomes durable benefit. The path forward is not only better constructs, but also smarter patient selection, better trial paradigms that evaluate multiple innovations efficiently, and survivorship models that treat immune recovery as a long-term therapeutic objective.