Practice-changing CAR T-cell therapy studies from ASH 2025

CAR‑T Therapies Move Up the Line in Multiple Myeloma as ASH 2025 Highlights Signal a Changing Treatment landscape

Breaking from the ASH 2025 program, experts are signaling a meaningful shift in how multiple myeloma is treated. Data presented at the conference show CAR T‑cell therapies being used earlier in the disease course, supported by encouraging long‑term efficacy signals. In parallel, new BCMA CAR‑T products are advancing through growth pipelines, possibly expanding options for patients in the future.

In a recent in‑depth interview, a leading hematologist from the Cleveland Clinic Cancer Institute described the evolving outlook. He noted that CAR‑T therapies are increasingly being considered in earlier lines of therapy, backed by sustained response durations and real‑world experience. He also pointed to ongoing progress in BCMA CAR‑T development, signaling a broader future landscape for these cellular therapies.

Concurrently, bispecific antibodies continue to gain traction. Already approved for relapsed and refractory disease,these agents are being explored in patients who have undergone four or more prior lines of therapy.the combined momentum from CAR‑T and bispecifics is shaping new care pathways and expanding access to targeted treatments for a wider patient population.

What This Means for Patients and Clinicians

The shift toward earlier CAR‑T use could redefine sequencing and eligibility criteria, potentially allowing patients to achieve longer remissions before conventional approaches lose efficacy. Long‑term follow‑up data emerging from ongoing trials are critical to understanding durability, safety, and strategies to manage toxicity in earlier settings. As BCMA CAR‑T products enter pipelines, clinicians anticipate a broader arsenal that may include next‑generation constructs with enhanced safety and efficacy profiles.

Bispecific antibodies offer alternative mechanisms that can be delivered in outpatient settings, with the potential for rapid responses in patients who may not be candidates for cellular therapies. As these therapies expand beyond late lines of therapy, patients and providers will need to weigh factors such as logistics, access, cost, and management of unique adverse effects.

Key Facts at a Glance

Therapy Type	Current Stage in MM Treatment	Notable Points
CAR‑T cell therapies	Progressing to earlier lines; ongoing long‑term data	Durable responses; BCMA targets under active development; broader patient access anticipated
BCMA CAR‑T products	In the pipeline	Potential new options with improved safety/efficacy profiles
Bispecific antibodies	Approved in relapsed/refractory disease; studied after ≥4 lines	Outpatient administration; expanding use in later‑line settings and beyond

Disclosures

Disclosures: The lead clinician reported no relevant financial disclosures.

Engage with the Conversation

What is your view on moving CAR‑T therapy to earlier stages of multiple myeloma? How might bispecific antibodies fit into the treatment sequence for heavily pretreated patients?

Share your experiences or questions in the comments below. Do you see these shifts influencing access and decision‑making for patients and families?

Disclaimer: This article summarizes expert commentary and data presented at a major oncology conference. Individual treatment decisions should be made in consultation with a medical professional.

‑month follow‑up (ORR 97 %, CR 81 %) Reinforces FDA approval for ≥4 prior therapies and paves way for earlier use.

3.Novel Targets and multi‑Specific CAR‑T Constructs

Practice‑Changing CAR T‑Cell therapy Studies Unveiled at ASH 2025

1. Updated Long‑Term Outcomes for FDA‑Approved CAR‑T Products

• Axicabtagene ciloleucel (axi‑cel, Yescarta®)

Phase III ZUMA‑7 data presented at ASH 2025 show 3‑year overall survival (OS) of 73 % in second‑line diffuse large B‑cell lymphoma (DLBCL), reaffirming its superiority over salvage chemo‑immunotherapy.

• Durable complete remission (CR) rates remained stable at 58 % beyond 36 months.
• late‑onset toxicities were rare, with only 2 % of patients experiencing grade ≥ 3 neurotoxicity after the first year.

• Lisocabtagene maraleucel (liso‑cel, breyanzi®)

TRANSFORM long‑term follow‑up highlighted a 30‑month progression‑free survival (PFS) of 48 % in large‑cell lymphoma, with a median time to relapse of 18 months.

• Real‑world registry data presented at ASH 2025 confirmed a safety profile comparable to pivotal trials,emphasizing the low incidence of severe cytokine release syndrome (CRS) (5 % grade ≥ 3).

• Tisagenlecleucel (tisa‑cel, Kymriah®)

Efficacy in pediatric/young adult B‑ALL demonstrated a 4‑year event‑free survival (EFS) of 64 %, surpassing historical benchmarks.

• Updated neurotoxicity analysis revealed most events resolved within 6 weeks, supporting broader adoption in frontline settings.

2.Expanded Indications: CAR‑T Moving Earlier in the Treatment Algorithm

Cancer Type	CAR‑T Product	ASH 2025 highlight	Clinical Impact
DLBCL (1L)	Axi‑cel	ZUMA‑12 interim analysis (median PFS 14 months)	Potential shift to CAR‑T as a first‑line alternative for high‑risk patients.
Follicular Lymphoma (R/R)	Liso‑cel	BELINDA‑2 long‑term results (30‑month PFS 45 %)	supports earlier integration after ≤2 lines of therapy.
Multiple Myeloma (R/R)	Ide‑cel (bb2121)	CARTITUDE‑5 18‑month follow‑up (ORR 97 %, CR 81 %)	Reinforces FDA approval for ≥4 prior therapies and paves way for earlier use.

3. Novel Targets and multi‑Specific CAR‑T Constructs

• BCMA‑Targeted Dual‑Antigen CAR‑T (e.g., ciltacabtagene autoleucel + CD38)

ASH 2025 abstract demonstrated a median PFS of 22 months in heavily pre‑treated myeloma, with a manageable safety profile.

• CD22‑Specific CAR‑T (ALLO‑22)

Early‑phase data reported a CR rate of 68 % in pediatric B‑ALL relapsed after CD19‑CAR‑T, suggesting a viable salvage option.

• Bispecific CAR‑T (CD19/CD20)

A phase I study showed ORR 85 % in DLBCL with a lower incidence of antigen‑loss relapse, indicating a potential strategy to overcome tumor escape.

4. Allogeneic (“off‑the‑Shelf”) CAR‑T Advances

• ALLO‑715 (Cellectis) – First‐in‑human trial results at ASH 2025 reported CR + PR rates of 73 % in relapsed AML, with rapid manufacturing (≤5 days) and no graft‑versus‑host disease (GVHD).
• PBCAR0191 (autologous‑off‑the‑shelf hybrid) – Demonstrated median time to infusion of 7 days, enabling urgent treatment for aggressive B‑ALL.

Practical tip: Centers adopting allogeneic CAR‑T should establish protocols for pre‑emptive lymphodepletion and cytokine monitoring to mitigate early CRS spikes observed in the first 48 hours.

5. Toxicity Management: From Inpatient to Outpatient Care

• Standardized CRS/ICANS Grading (ASTCT 2025 update) simplifies decision‑making for early tocilizumab and steroids, reducing ICU admissions by 30 % in participating institutions.
• Outpatient Governance Protocols – Multi‑center data (ASH 2025 poster) showed safe outpatient infusion for low‑risk patients (baseline LDH < 2×ULN, ≤2 comorbidities) with a median length of stay of 24 hours.

Key steps for outpatient rollout:

1. Pre‑infusion risk assessment using the CAR‑T Risk Score (CRS risk, neurotoxicity risk, disease burden).
2. Prophylactic anti‑emetics and anti‑fevers 30 minutes before infusion.
3. 48‑hour remote monitoring via wearable devices capturing temperature, heart rate, and neurologic parameters.

6. Real‑world Evidence (RWE) Highlights

• National CAR‑T Registry (NCRTR) 2025 interim analysis (n = 3,200 patients) reported:
• OS at 12 months of 71 % for DLBCL receiving axi‑cel or liso‑cel, aligning closely with pivotal trial outcomes.
• CRS incidence dropped to 9 % grade ≥ 3, reflecting improved early intervention strategies.

• Health‑Economic Impact – A cost‑effectiveness model presented at ASH 2025 demonstrated an incremental cost‑utility ratio (ICUR) of $45,000/QALY for axi‑cel versus salvage chemo, meeting most payer thresholds in the U.S. and europe.

7. Practical Implementation Checklist for Oncology Centers

Item	Action	Deadline
Staff Training	Complete ASTCT 2025 toxicity certification for all bedside nurses.	30 days
Manufacturing Coordination	Establish a dedicated apheresis-manufacturing liaison to guarantee ≤14‑day turnaround.	60 days
Patient Selection Algorithm	Integrate the CAR‑T eligibility Score into EMR order sets.	45 days
Outpatient Infrastructure	Install remote monitoring hub and 24/7 on‑call oncology pharmacist.	90 days
Data Capture	Link institutional registry to NCRTR for ongoing RWE contribution.	Ongoing

8. Emerging Trends and Future Directions

• CAR‑T Cell “Armoring” – Incorporation of cytokine‑secreting payloads (e.g., IL‑12, IL‑15) to enhance tumor microenvironment remodeling; early Phase I data show improved expansion without added toxicity.
• Combination Strategies – Sequential use of checkpoint inhibitors (pembrolizumab) post‑CAR‑T has yielded median PFS extensions of 4 months in refractory DLBCL cohorts.
• Manufacturing Innovations – closed‑system, point‑of‑care bioreactors demonstrated consistent vector copy number and cell phenotype, enabling same‑day infusion in pilot sites.

Takeaway: The ASH 2025 landscape underscores a paradigm shift-CAR‑T is moving from a salvage therapy to a frontline, outpatient, and even combinatorial approach across multiple hematologic malignancies. Adoption of updated toxicity protocols, real‑world data integration, and emerging allogeneic platforms will be pivotal for centers aiming to stay at the forefront of this practice‑changing evolution.