Time to Next Treatment in CAR T-Cell Therapy: A Real-World Outcome Shaping Value and Clinical Decision-Making

Emerging real-world data in chimeric antigen receptor (CAR) T-cell therapy suggest that traditional efficacy end points may not fully capture treatment durability or downstream clinical burden.¹ An increasingly used metric is time to next treatment (TTNT), which reflects the interval between CAR T infusion and the initiation of subsequent anticancer therapy. Prior data suggest TTNT may serve as a pragmatic indicator of durability, health care use, and real-world treatment effectiveness in patients with relapsed or refractory hematologic malignancies.¹

CAR T-Cell Therapy in Heavily Pre-Treated Patients

The treatment landscape for patients with relapsed or refractory large B-cell lymphoma and multiple myeloma, particularly in those who have exhausted standard chemotherapy, immunotherapy, and targeted agents, has transformed due to CAR T-cell therapy. Agents such as idecabtagene vicleucel (ide-cel, Abecma; Celgene Corporation) and lisocabtagene maraleucel (liso-cel, Breyanzi; Juno Therapeutics, Inc) redirect autologous T cells to target tumor-associated antigens such as BCMA or CD19, resulting in deep and often durable responses in otherwise refractory disease.^2,3

Despite high response rates, relapse and disease progression remain clinically significant challenges. As a result, real-world outcome measures such as TTNT are increasingly important for understanding how long patients remain treatment-free following CAR T infusion.¹

What Is TTNT? Why It Matters

TTNT is defined as the time from CAR T-cell infusion to initiation of the next line of anticancer therapy. Unlike progression-free survival (PFS), it is not dependent on imaging schedules or standardized assessment intervals, making it a pragmatic real-world end point used in observational oncology and claims-based analyses.^1,2 TTNT is often used as a surrogate measure of treatment durability and time spent free from subsequent systemic therapy in real-world settings.²

Multiple clinical factors influence TTNT by affecting both disease course and postinfusion recovery trajectories. These include the depth and durability of responses following CAR T-cell therapy, as demonstrated in pivotal trials of CAR T products in lymphoma and multiple myeloma.³ Disease biology and early relapse patterns similarly play a central role in determining duration of response and subsequent treatment initiation.³

Postinfusion toxicities, such as cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS), may impact recovery trajectories and influence downstream treatment timing, primarily in patients requiring prolonged hospitalization or intensive supportive care.⁴ These factors collectively contribute to variability in TTNT observed across clinical trials and real-world populations.

TTNT reflects both disease-related outcomes and the posttreatment clinical course and is increasingly considered a pragmatic indicator of real-world therapeutic durability and overall treatment burden in CAR T-treated patients.^2,4

Clinical Observations

Findings from real-world analyses of patients treated with CAR T-cell therapy indicate that TTNT varies substantially based on baseline disease characteristics, prior lines of therapy, and postinfusion clinical outcomes. In observational cohorts of CAR T-cell therapy recipients, patients with lower disease burden at infusion and more favorable baseline characteristics are more likely to achieve deeper, more durable responses, which is associated with prolonged treatment-free intervals.^1,2 Heavily pretreated patients or those with more aggressive disease biology tend to experience shorter durations of response and earlier initiation of subsequent therapy.¹

Achieving a complete response following CAR T-cell therapy has consistently been associated with more durable disease control when compared with partial response or nonresponse states.³ In this context, TTNT functions as a downstream reflection of response depth, as patients who achieve and maintain complete remission generally remain treatment free for longer periods before requiring additional systemic therapy.^2,3

Postinfusion toxicities play an important indirect role in shaping TTNT, alongside disease biology and response depth. CRS and ICANS are among the most clinically significant early complications following CAR T-cell therapy and may require intensive monitoring, hospitalization, or critical care support.⁴ While these toxicities are not direct drivers of relapse, their severity and duration can delay clinical recovery, prolong inpatient stays, and influence timing of subsequent treatment decisions in patients with suboptimal or transient responses.⁴

Infections represent another critical contributor to postinfusion clinical complexity, particularly during the period of immune reconstitution following lymphodepleting chemotherapy and CAR T-cell therapy infusion. Infectious complications may further prolong hospitalization or necessitate treatment interruption and escalation of supportive care, thereby indirectly influencing TTNT in real-world settings where treatment pathways are not protocol driven.⁴

Collectively, these real-world observations support TTNT as a downstream indicator of clinical durability that extends beyond traditional trial end points. Within commercial CAR T programs, TTNT is increasingly incorporated into broader assessments of real-world effectiveness and health care use. For agents such as ide-cel and liso-cel, TTNT provides an additional lens through which durability can be evaluated alongside established endpoints such as overall response rate and PFS.^2,3

TTNT also complements other real-world metrics, including health care resource use, infection-related hospitalization rates, early postinfusion adverse event profiles, and treatment center access and geographic variability.^2,3 Together, these measures provide a more comprehensive understanding of CAR T performance in routine clinical practice, capturing both therapeutic durability and system-level drivers of patient outcomes.

REFERENCES

1. Nastoupil LJ, Jain MD, Feng L, et al. Standard-of-care axicabtagene ciloleucel for relapsed or refractory large B-cell lymphoma: results from the US Lymphoma CAR T Consortium. J Clin Oncol. 2020;38(27):3119-3128. doi:10.1200/JCO.19.02104

2. Munshi NC, Anderson LD Jr, Shah N, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med. 2021;384(8):705-716. doi:10.1056/NEJMoa2024850

3. Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020;396(10254):839-852. doi:10.1016/S0140-6736(20)31366-0

4. Neelapu SS, Tummala S, Kebriaei P, et al. Chimeric antigen receptor T-cell therapy - assessment and management of toxicities. Nat Rev Clin Oncol. 2018;15(1):47-62. doi:10.1038/nrclinonc.2017.148