Abstract
Talicabtagene autoleucel (tali-cel) is the first humanized CD19-directed CAR-T cell therapy approved in India for relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) and B-cell non-Hodgkin lymphoma (B-NHL). Here, we integrated clinical and manufacturing operations through a centralized coordination unit (CCU) and evaluated tali-cel implementation. Patients with r/r B-ALL (n = 105) and r/r B-NHL (n = 145) who underwent leukapheresis between 15 November 2023 and 31 January 2025 across 56 treatment centers were included. The CCU enabled timely delivery, with manufacturing slot allocation within one week of slot request and a median vein-to-vein time of 29 days (range, 16–102), independent of geographic location. In r/r B-ALL patients, the median follow-up was 14 months, and the median overall survival (OS) not reached, and progression-free survival (PFS) was 18 months (range: 9-NR). The 12-month OS and PFS were 64% (95% CI: 53–72) and 55% (95% CI: 45–65). In r/r B-NHL, the median follow-up was 13 months and the median PFS was 11 months (range:7–16) and OS was not reached. The 12-month OS and PFS were 63% (95% CI: 54–71) and 47% (95% CI: 38-56). No patients underwent consolidative stem cell transplantation. Grade 3/4 cytokine release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome (ICANS), and Immune Effector Cell-associated Hemophagocytic Lymphohistiocytosis-like Syndrome (IEC-HS) occurred in 6%, 4%, and 23% of r/r B-ALL and 6%, 3%, and 18% of r/r B-NHL patients, respectively. These findings demonstrate the successful implementation of tali-cel across multiple centers in a large cohort, which might contribute towards improving CAR-T access globally.
Subject terms: Immunotherapy, Haematological cancer
Introduction
In 2022, about 90,000 people were diagnosed with Non-Hodgkin’s Lymphoma (NHL) and leukemia in India, and an estimated 30,000 patients will develop relapsed/refractory (r/r) disease and require salvage therapy [1–3]. The outcomes of r/r B-cell malignancies are dismal due to the limited access of salvage therapies and a very low stem-cell transplant rate [4–6]. CD19-targeted CAR-T cell therapy holds promise in improving outcomes for r/r B-cell malignancies in India. In October 2023, talicabtagene autoleucel (tali-cel) was granted accelerated approval for commercial use in r/r B-cell malignancies in India, making it the first CD19-targeted therapy in India [7–9].
In pivotal trials, tali-cel demonstrated durable responses (73% overall response rate, ORR) and low incidence of toxicities such as cytokine release syndrome (CRS, Grade 3–4: 5%) and immune-effector cell-associated neurotoxicity syndrome (ICANS, Grade 3–4: none) [10]. The favorable safety profile led to a low intensive care unit (ICU) admission rate and reduced hospital stay [11]. These features coupled with the low product costs were expected to ease the delivery of tali-cel and enhance access to CAR-T cell therapy in our region [9, 12]. Despite strong clinical promise, CAR-T cell therapies face access challenges, driving exploration of ease-of-access models even in developed nations [13]. Given the limited healthcare resources and limited options for r/r B-cell malignancies in India, it is even more critical to develop a scalable, reproducible, and sustainable delivery framework to ensure timely access.
Given the limited sample size of the pivotal trial, evaluation of tali-cel in routine practice is essential to support its adoption as a standard of care (SOC). We therefore implemented a centralized, ease-of-access model for tali-cel via a Centralized Coordinating Unit (CCU) and conducted a multicenter real-world study to assess its safety, efficacy, and feasibility as an SOC in resource-constrained settings.
Methods
Study design and participants
Since the approval of tali-cel, a centralized database of all the patients planned for tali-cel has been maintained in accordance with regulatory guidance. This retrospective multicenter analysis included data from 56 centers to evaluate efficacy, safety, healthcare resource utilization (HCRU), and real-world access to tali-cel as standard of care (SOC). The study was approved by the institutional ethics committee and registered with the Clinical Trials Registry of India (CTRI/2025/08/093795); written informed consent and data-sharing agreements were obtained at participating centers. Patients undergoing leukapheresis between 15 November 2023 and 31 January 2025 were included, with the database locked on 31 March 2026. Eligible patients were aged ≥15 years with relapsed/refractory B-ALL or B-NHL, including diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (tFL), primary mediastinal large B-cell lymphoma (PMBCL), follicular lymphoma (FL) grade 3B, high-grade B-cell lymphoma (HGBL), and indolent B-cell lymphoma.
Ease-of-access model framework
A centralized coordinating unit (CCU) was established to facilitate the training and affiliation of centers. The clinical centers were located across the country. Fortnightly, virtual tumor boards (VTB) were conducted using the national cancer grid (NCG) and moderated by experienced clinicians. Tali-cel was manufactured at a centralized cGMP facility, with validated cold-chain logistics across all sites.
Manufacturing efficiency was assessed using apheresis failure rates, manufacturing success rate (MSR), decision-to-vein time (DTV; interval from slot request to infusion), vein-to-vein time (VTV; interval from leukapheresis to infusion), and the impact of distance from the manufacturing site.
Clinical assessment—safety and efficacy
Patients received a single tali-cel infusion at a target dose of ≥5 × 10⁶ CAR-T cells/kg following lymphodepletion with fludarabine 30 mg/m² and cyclophosphamide 500 mg/m² for three consecutive days. Bridging therapy, consolidation, and maintenance therapies were administered at physician discretion.
Data were collected at baseline, pre-infusion, day 28, and months 3, 6, 9, and 12, and annually thereafter for up to 5 years. Responses were assessed at day 28 and day 90 on physicians’ discretion.
Assessment of outcomes
Progression-free survival (PFS) was defined as the duration from leukapheresis to relapse/progression, or tali-cel–related death, and overall survival (OS) as the duration from leukapheresis to death from any cause. Complete Responses (CR) and Complete Responses incomplete hematologic recovery (CRi) were grouped and reported as CRs. Patients without events were censored at last follow-up.
Response in r/r B-ALL was assessed by bone marrow evaluation, and in r/r B-NHL by ¹⁸F-FDG PET-CT using Lugano criteria. Safety assessments included Cytokine release syndrome (CRS), Immune-effector Cell Associated Neurotoxicity Syndrome (ICANS), and Immune-effector cell-associated haemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) graded per ASTCT criteria [14], and cytopenias graded per CTCAE v5.0. Health Care Resource Utilization (HCRU) was assessed through hospital records for hospitalization,Intensive Care Unit (ICU) admission, and supportive care requirements.
Statistical analysis
All patients undergoing leukapheresis were included in manufacturing analyses, while infused patients were included in safety, efficacy, and HCRU analyses. Descriptive statistics with 95% confidence intervals (Wilson/Brown) summarized outcomes. Group comparisons used chi-square or Fisher’s exact tests. Cox regression identified prognostic factors, with variables at p < 0.1 included in multivariate models. Survival was estimated using Kaplan–Meier methods and compared using log-rank or Wilcoxon tests. Analyses were performed using R and GraphPad Prism v11.0.1.
Results
Patient characteristics
As of 31st January 2025, 250 patients with r/r B-cell malignancy (B-ALL, n = 105, B-NHL, n = 145) across 56 treatment centers underwent leukapheresis with an intent to receive tali-cel. The baseline characteristics are summarized in Table 1. Prior to leukapheresis, patients had received a median two prior lines of therapy (range: 1–7).
Table 1.
Demographics, baseline characteristics, and tumor burden of the patients in real world intended to treat with tali-cel.
| Characteristics | B-ALL (n = 105) | B-NHL (n = 145) |
|---|---|---|
| Age, years Median (range) | 25 (15-64) | 55 (17-83) |
| Sex, n (%) | ||
| Male | 79 (75) | 89 (61) |
| Female | 26 (25) | 56 (39) |
| Prior Line of therapy | ||
| Median, n (range) | 2 (1–7) | 2 (1–7) |
| 1, n(%) | 25 (24) | 24 (17) |
| 2, n(%) | 45 (43) | 51 (35) |
| ≥3, n(%) | 35 (33) | 70 (48) |
| Prior SCT, n (%) | 9 (9) | 12 (8) |
| Disease type, n (%) | ||
| Primary Refractory | 31 (30) | 54 (37) |
| Early Relapse | 26 (25) | 55 (38) |
| Late relapse | 26 (25) | 23 (16) |
| Unknown | 22 (20) | 13 (9) |
| Bridging therapy, n (%) | 90 (86) | 121 (83) |
| Leukemia specific characteristics | ||
| Disease burden prior apheresis | ||
| Median % blast (range) prior apheresis | 2% (0–96) | – |
| Morphological Disease, (Leukemia Blasts ≥5%) | 37 (35) | – |
| MRD negative by flowcytometry prior apheresis, n (%) | ||
| Yes | 42 (40) | – |
| No | 50 (48) | – |
| Unknown | 13 (12) | – |
| Leukemia Disease subtype, n (%) | ||
| Ph +ve | 26 (25) | – |
| Ph like | 11 (10) | – |
| Ph –ve | 58 (55) | – |
| Unknown | 10 (10) | – |
| Prior immunotherapy, n (%) | ||
| Prior blinatumomab therapy | 3 (3) | – |
| Prior inotuzumab ozogamicin therapy | 36 (34) | – |
| CNS disease prior apheresis, n (%) | ||
| Yes | 11 (10) | – |
| No | 90 (86) | – |
| Unknown | 4 (4) | – |
| Lymphoma specific characteristics | ||
| Lymphoma disease histology, n (%) | ||
| DLBCL | – | 95 (66) |
| HGNHL | – | 20 (14) |
| PMBCL | – | 7 (5) |
| tFL | – | 7 (5) |
| MCL | – | 5 (3) |
| FL | – | 10 (7) |
| MZL | – | 1 (<1) |
| Tumor burden prior apheresis, n (%) | ||
| Bulky disease (Tumor bulk ≥5 cm) | – | 53 (37) |
| Extranodal sites prior apheresis, n (%) | ||
| 1 EN sites | – | 58 (40) |
| ≥2 EN sites | – | 21 (15) |
| No EN | – | 56 (38) |
| Unknown | – | 10 (7) |
| IPI prior apheresis, n (%) | ||
| ≤2 risk factors | - | 105 (72) |
| ≥3 risk factors | - | 40 (28) |
| Prior immunotherapy, n (%) | ||
| Prior polatuzumab vedotin therapy | – | 21 (14) |
| Prior glofitamab therapy | – | 5 (3) |
| Response to prior therapy, n(%) | ||
| CR | – | 18 (12) |
| PR | – | 22 (15) |
| SD | – | 6 (4) |
| PD | – | 92 (64) |
| Unknown | – | 7 (5) |
SCT stem cell transplant, Ph Philadelphia chromosome, MRD measurable residual disease, CNS central nervous system.
Primary refractory = did not achieve CR after one or two cycles of initial therapy, Early relapse = relapse within 12 months of initial therapy, Late relapse = relapse beyond 12 months of initial therapy.
For r/r B-ALL patients, SCT, inotuzumab (InO), and blinatumomab exposure prior to leukapheresis occurred in 9% (9/105), 34% (36/105), and 3% (3/105) patients, respectively. Median blast percentage at enrollment was 2% (range: 0–96%). Morphologic disease (≥5% blasts) was present in 35% (37/105), 40% (42/105) were MRD negative prior to leukapheresis, 30% (31/105) had primary refractory disease (did not achieve CR after one or two cycles of initial therapy), and 10% had prior CNS involvement.
In r/r B-NHL, DLBCL was the predominant histology (66%, 95/145), followed by high-grade lymphomas (14%, 20/145); indolent lymphomas accounted for 11% (16/145). Nearly half received tali-cel after third-line failure (48%, 70/145), 37% (54/145) had primary refractory disease 37% (53/145) had bulky disease (Tumor bulk ≥5 cm), and 15% (21/145) had extranodal involvement. Progressive disease prior to leukapheresis was observed in 63% (92/145), and 28% (40/145) had ≥3 IPI risk factors.
At data cutoff, 98 r/r B-ALL and 128 r/r B-NHL patients received tali-cel and were evaluable for safety and efficacy. Eighteen patients died before infusion (B-ALL, n = 6; B-NHL, n = 12), and six experienced manufacturing failure (Supplementary Fig. 1). Patients who did not receive tali-cel included those with r/r B-ALL (n = 7), who were relatively older (median 39 years), had received ≥2 prior lines of therapy, and had persistent MRD-positive disease with a median baseline blast burden of 4%. In r/r B-NHL (n = 17), most patients had aggressive disease biology, including a predominance of high-grade histologies (DLBCL 65% (11/17), HGNHL 12% (2/17)), primary refractory status (59% (10/17)), and bulky disease in approximately half of the cohort (Supplementary Table 3). All patients received Flu–Cy lymphodepletion except six who received bendamustine. Bridging therapy was administered to 93% (211/226).
Implementation and ease-of-access metrics
The CCU enabled training and affiliation of 56 centers nationwide. Tier 1 center (population ≥5 million) accounted for 66% (37/56) of patients (Fig. 1A). Centers proximal to manufacturing (<500 km; n = 12) recruited 53% (133/250) of patients, while intermediate (500–1000 km; n = 20) and distal (>1000 km; n = 24) centers enrolled 17% (42/250) and 30% (75/250), respectively.
Fig. 1. The enabling access model for tali-cel in India.
A Schematic depicting the centralized manufacturing and access model for tali-cel in India with key elements: central coordinating unit (CCU) and Treatment centers marked with Tier status of the centers. B MSR of tali-cel in real-world settings, green (overall, 98%, 244/250), blue (MSR in one attempt, 94%, 229/244). C Decision to vein (DTV) time and D Vein to vein (VTV) time for patients infused with Tali-cel, distributed as per geographic strata (Tier 1 and Tier 2) and location of cancer center (Proximal, Intermediate, and Distal) from the central manufacturing site.
Leukapheresis material was shipped at 2–8 °C within 24 h, and cryopreserved CAR-T products were delivered without logistics failures. The overall manufacturing success rate (MSR) was 98% (244/250; 95% CI: 94–99) (Fig. 1B). Single-attempt manufacturing met specifications in 94% (229/244); 15 required repeat attempts due to transduction/expansion failure (n = 9) or sterility failure (n = 6). Repeat leukapheresis was required in 3% (8/244).
The median DTV was 33 days (range: 22–97) across all patients (Fig. 1C). The median VTV was 29 days (range: 16–102), thus highlighting minimum wait-time for slot allocation (Fig. 1D). Treatment centers located in Tier 2 cities had a median DTV and VTV of 32 days and 28 days respectively, comparable to the Tier 1 centers. The proximal treatment centers had DTV and VTV of 34 days and 29 days, respectively, comparable in the treatment centers with intermediate vicinity as well as distal treatment centers (Fig. 1C, D).
Outcomes
Safety
Within 1 month of infusion, grade 3–4 cytopenias occurred in 76% (74/98) r/r B-ALL and 77% (98/128) r/r B-NHL patients (Table 2).
Table 2.
Incidence and severity of common adverse events and key healthcare resource utilization for clinical management in all patients infused with tali-cel.
| Event, n (%) | B-ALL (n = 98) | B-NHL (n = 128) |
|---|---|---|
| CRS | ||
| Any grade | 76 (78) | 107 (84) |
| Grade 1–2 | 70 (72) | 99 (77) |
| Grade 3–4 | 6 (6) | 8 (6) |
| ICANS | ||
| Any grade | 7 (7) | 14 (11) |
| Grade 1–2 | 3 (3) | 10 (8) |
| Grade 3–4 | 4 (4) | 4 (3) |
| ≥Grade 3 Cytopenia | 74 (76) | 98 (77) |
| Hypogammaglobinemia | 55 (56) | 71 (55) |
| IEC-HS | 23 (23) | 23 (18) |
| Toxicity management | ||
| Hospitalization, Median (range) days | 8 (1–67) | 12 (1–73) |
| ICU admissions | 9 (9) | 7 (5) |
| Median duration of ICU stay,(range) days | 4 (2–55) | 12 (3-26) |
| Tocilizumab, n (%) | 68 (69) | 64 (50) |
| Median no. of doses (range) | 1(1–4) | 1(1–4) |
| Vasopressors, n (%) | 5 (5) | 11 (9) |
| Corticosteroid, n (%) | 17 (17) | 26 (20) |
| Anakinra, n (%) | 26 (27) | 23 (18) |
| IVIG, n (%) | 59 (60) | 66 (52) |
In r/r B-ALL, CRS occurred in 78% (76/98), with grade 3–4 CRS in 6% (6/98) and grade 3–4 ICANS in 4% (4/98). Any-grade IEC-HS occurred in 23% (23/98). Hypogammaglobulinemia (IgG <600 mg/dL) developed in 56% (55/98), and B-cell aplasia in 77% (48/62). Median hospitalization was 8 days (range: 1–67); ICU admission occurred in 9% (9/98), with median ICU stay of 4 days (range: 2–55).
Tocilizumab was used in 69% (68/98), with a single dose sufficient in 70% (48/68). Corticosteroids, vasopressors, and anakinra were required in 17% (17/98), 5% (5/98), and 27% (26/98), respectively. IVIG was administered in 60% (59/98).
In r/r B-NHL, grade 3–4 CRS and ICANS occurred in 6% (8/128) and 3% (4/128), respectively. Any-grade IEC-HS and hypogammaglobulinemia occurred in 18% (23/128) and 55% (18/128). B-cell aplasia was present in 68% (59/87). Median hospitalization was 12 days (range: 1–73); ICU admission occurred in 5% (7/128), with median ICU stay of 12 days.
Tocilizumab was used in 50% (64/128), with a median of one dose (range: 1–4); 75% (48/64) required a single dose. Corticosteroids, vasopressors, anakinra, and IVIG were used in 20% (26/128), 9% (11/128), 18% (23/128), and 52% (66/128), respectively.
Efficacy
For r/r B-ALL, day 28 ORR was 88% (86/98) (95% CI:80-93); of whom 86% (84/98) achieved a CR (Fig. 2A). Of the 79 patients evaluated for MRD by flowcytometry, 92% (73/79) demonstrated a MRD clearance. On day 90, 75% (73/98, 95% CI:65-82) patients showed an overall response (ORR), with 73% (72/98) patients in CR.
Fig. 2. Tali-cel shows durable efficacy and survival outcomes in B-ALL.
A The ORR in the efficacy evaluable cohort for B-ALL (n = 98) evaluated at Day 28 (ORR:88%) and Day 90 (ORR:75%) categorized as Response (CR + PR), Progressive Disease (PD) and not evaluable (NE) including death. B Progression free survival (PFS) and (C) Overall survival (OS) for all efficacy evaluable patients by Kaplan-Meier method from enrollment and patients were censored at subsequent therapy. The median PFS was 18 months and median OS was not reached with two patients of longest follow-up in remission at 27 months. The shaded area depicts 95% CI.
At median follow-up of 14 months (range: 1-27), the median PFS was 18 months (range: 9-NR) and OS was not reached (Fig. 2B, C). The 6-month OS and PFS were 82% (95% CI: 73-88) and 73% (95% CI: 64–81), respectively. At 12 months, 86% (51/59) patients evaluated continued to maintain the response. The 12-month OS and PFS were 64% (95% CI: 53–72) and 55% (95% CI: 45–65), respectively. Twenty-nine patients continue to maintain CR for beyond 18 months post infusion with longest remission upto 27 months.
On univariate analysis, MRD negativity at baseline and <5% blasts were associated with improved outcomes (p < 0.1), while InO exposure were associated with inferior PFS and OS; InO remained the strongest adverse factor on multivariate analysis for leukemia free survival (p < 0.05) (Supplementary Table 1) and these patients were heavily pretreated (Supplementary Table 4).
Overall response rate in r/r B-NHL patients was 75% (95% CI:67–82), (CR rate: 56%, 95%CI: 48–65) and 59% (95% CI:51–67), (CR rate: 55%, 95% CI:46–63) at day 28 and day 90 post tali-cel infusion (Fig. 3A). At a median follow-up of 13 months (range: 1-26), the median PFS was 11 months (range: 7–16), with median OS not reached for all B-NHL patients (Fig. 3B, C). The 12-month OS and PFS for all patients was 63% (95% CI: 54–71) and 47% (95% CI: 38–56), respectively. The patients achieving PR had median PFS and OS of 9 months (range: 4–12), respectively. For patients achieving CR by Day 90, the responses were durable, the median PFS and OS was not reached at data cut-off. For patients in CR, 86% (43/50) evaluated at 12 months continued to maintain the response. The 12-month PFS and OS for CR patients was 66% (95% CI: 56–76) and 80% (95% CI: 69–88). The patients (n = 2) with longest follow-up of 26 months continue to remain in remission.
Fig. 3. Tali-cel shows durable efficacy and survival outcomes in B-NHL.
A The ORR in the efficacy evaluable cohort for B-NHL (n = 128) evaluated at Day 28 (ORR:75%, CR:56%) and Day 90 (ORR:59%, CR:55%) categorized as Response (CR + PR), Progressive Disease (PD) and not evaluable (NE) including death. B Progression free survival (PFS) and C overall survival (OS) for all efficacy evaluable patients by Kaplan-Meier method from enrollment and patients were censored at subsequent therapy. The median PFS for all patients was 11 months and median OS was not reached. The median PFS and OS for PR patients (within Day 90) was 09 months, respectively. The median PFS and OS for CR patients (within Day 90) was not reached with two patients with longest follow-up patient in remission at 26 months. The shaded area depicts 95% CI.
Primary refractory disease in r/r B-NHL patients was cofounding factor responsible for inferior PFS and OS (p < 0.05) post tali-cel infusion as per multivariate analysis. Additional adverse prognostic factors included age ≥65 years, early relapses (relapse within 12 months to initial therapy) to prior therapy, bulky disease, and ≥3 factors of IPI at risk, were associated with poorer survival outcomes (Supplementary Table 2). In patients with r/r B-NHL, response (CR/PR) to the most recent prior therapy was associated with significantly longer PFS and OS (p < 0.05) and disease histology of DLBCL vs HGNHL had comparable outcomes.
Subsequent therapy
In patients with r/r B-ALL, none underwent allogeneic stem cell transplantation as consolidation following tali-cel infusion. Forty-five patients (46%) received subsequent therapy after a single infusion of tali-cel, including maintenance (25%, 24/98), loss of B-cell aplasia (9%, 9/98), or relapse (12%, 12/98). Maintenance strategies primarily consisted of oral 6-MP/MTX (n = 15) and InO (n = 1) and TKI inhibitors (n = 8). Treatment for all patients with loss of B-cell aplasia was low-dose chemotherapy and in combination with reinfusion with tali-cel (n = 3). Management of relapse varied and included tali-cel (n = 1), mini-hyper-CVD followed by allogeneic stem cell transplantation (n = 2), low-dose chemotherapy (n = 4), InO (n = 3), daratumumab (n = 1), and blinatumomab (n = 1).
In r/r B-NHL, 48% (61/128) received subsequent therapy. Maintenance was administered in 27% (34/128), most commonly nivolumab (68%, 23/34), alone (n = 17) or with TKI (n = 6). Other maintenance regimens included lenalidomide plus TKI (n = 1), polatuzumab with glofitamab (n = 2), and TKI monotherapy (n = 8). One patient received nivolumab regimen as consolidation. Treatment for disease progression (n = 23) was heterogeneous and included combinations of radiotherapy and monoclonal antibody–based regimens, such as nivolumab, polatuzumab, obinutuzumab, glofitamab, pembrolizumab, and TKIs.
Discussion
In this study, we demonstrate, for the first time, the real-world feasibility of delivering a CD19-directed CAR-T cell therapy (tali-cel) through a centralized ease-of-access model across heterogenous healthcare settings in India. Beyond evaluating the safety and effectiveness of tali-cel, this work addresses a broader translational challenge: how complex cellular therapies can be implemented at a national scale in resource-limited health systems without compromising timelines, quality, and by virtue, outcomes.
A key finding is that centralized manufacturing, supported by a dedicated Centralized Coordinating Unit (CCU), enabled tali-cel delivery independent of geographic proximity, or institutional size. Treatment was successfully implemented across 56 cancer centers including large tertiary hospitals, medium-sized oncology centers, BMT-enabled and non-BMT centers, and academic institutions in a very short duration (~one year). Notably, most treatment centers were located at distances exceeding 500 km from the centralized manufacturing facility and over 30% of participating centers in Tier II cities (Fig. 1), underscoring the scalability and geographic reach of this model.
The CCU played a pivotal role in center affiliation, training, and monthly manufacturing slot allocation based on clinical urgency and logistics. In parallel, a nationwide advisory network operating through virtual tumor boards (VTBs) in coordination with the National Cancer Grid (NCG) ensured standardized patient selection and peri-infusion management. This coordinated oversight enabled uniform clinical practice across diverse healthcare centers.
Overall, 250 patients underwent leukapheresis, with a low attrition rate of around 10% prior to tali-cel infusion. The overall manufacturing success rate (MSR) was 98%, with 94% of products successfully manufactured on the first attempt. Importantly, no manufacturing failures were attributable to logistics-related constraints.
Treatment timelines further highlight the effectiveness of centralized coordination. The median decision-to-vein time was 33 days, and the median vein-to-vein time was 29 days, with CAR-T slot allocation typically occurring within one week of referral or intent-to-treat (Fig. 1C, D). These timelines were independent of geographic distance from the manufacturing facility and compare favorably with reported wait times of 4–8 weeks for leukapheresis slot allocation for FDA-approved CAR-T therapies [15–17]. Together, these findings support centralized manufacturing as a viable strategy to overcome logistical barriers in resource-limited settings.
Tali-cel was infused in 226 patients (r/r B-ALL, n = 98; r/r B-NHL, n = 128) with a median follow-up of 14 months and 13 months, respectively.
The clinical characteristics of patients, particularly in r/r B-ALL, reflect a shift toward earlier CAR-T utilization compared to patients treated with brexu-cel and tisa-cel in the real-world settings [18, 19]. The median age in the tali-cel cohort was 25 years (Table 1), and patients had received a median of two prior lines of therapy, with prior SCT (9%) and blinatumomab exposure in only 3% patients [17, 18]. Notably, 24% of patients received tali-cel as second-line therapy.
The median blast percentage was 2% (range 0–96), with 35% of patients having morphologic disease (≥5% blasts) and 40% being MRD-negative by flow cytometry highlighting similarities in treated populations to other real-world studies [18, 20].
Clinically, tali-cel demonstrated durable activity in r/r B-ALL. The 12-month OS and PFS were 64% and 55%, respectively, comparable to brexu-cel and tisa-cel [18, 20]. At 12 months, 51 of 59 evaluable patients remained in remission, with the longest remission extending to 27 months at last follow-up (Fig. 2).
Improved outcomes were observed in patients with MRD negativity and morphologic remission at baseline, while prior exposure to inotuzumab ozogamicin was associated with inferior survival (Supplementary Table 1) [21].
The favorable safety profile was established in the real-world setting. Grade 3–4 CRS and Grade 3–4 ICANS occurred in 6% and 4% of patients, lower than reported with brexu-cel and tisa-cel. Grade 3–4 cytopenias were observed in 76% of patients, and IEC-HS occurred in 23%, both of which were manageable with standard supportive care, including anakinra, ruxolitinib, and steroids (Table 2) [18, 20, 22].
In r/r B-NHL, baseline patient characteristics were broadly comparable to those reported in real-world studies of axi-cel, liso-cel, and tisa-cel [17, 23–25]. However, some differences were noted such as a higher proportion of patients with bulky disease (≥5 cm), a median of two prior lines of therapy and fewer (8%) patients who had underwent SCT in the past (Table 1) [23]. Most of the patients had aggressive histology (DLBCL and HGNHL) with less than 10% with low-grade lymphomas.
In r/r B-NHL, median PFS was 11 months and OS was not reached, with 12-month OS and PFS of 63% and 47%, respectively [24]. Among patients achieving CR, median PFS and OS were not reached, with durable remissions extending to 26 months; 12-month OS and PFS were 80% and 66%, respectively, comparable to other CAR-T products in real-world use (Fig. 3) [24, 25].
Response to prior therapy predicted superior outcomes, whereas age ≥65 years, primary refractory disease or early relapse, and high-risk IPI (≥3) were associated with inferior survival, consistent with other real-world CAR-T studies [17].
In r/r B-NHL, Grade 3–4 CRS and Grade 3–4 ICANS occurred at rates comparable to or lower than those reported with axi-cel, tisa-cel and liso-cel [25] (Table 2).
The favorable safety profile of tali-cel led to overall low utilization of healthcare resources for both the cohorts (Table 2). The ease of delivery of tali-cel was emphasized with a short duration of hospitalization (median 8-12 days). Only 5–9% of the patients required ICU admission (median 4 days, Table 2) which was lower in comparison to the other CAR-T cell products [17, 26].
The patients treated with tali-cel in both r/r B-ALL and r/r B-NHL reflect a broader global shift in clinical practice, wherein, within 2 years of its real-world availability, it is been increasingly deployed at a lower disease burden and earlier in the treatment, as a consolidation strategy owing to improved efficacy and a more favorable toxicity profile [27–29]. In this context, maintenance therapy following a single infusion of tali-cel was administered in 24% of r/r B-ALL and 27% of r/r B-NHL patients. In r/r B-ALL, maintenance predominantly consisted of oral 6-mercaptopurine and methotrexate, with only one patient receiving an inotuzumab-based regimen, consistent with patterns reported for other approved CAR-T therapies. In r/r B-NHL, nivolumab was the most used maintenance approach.
A notable strength of this study is the ability to evaluate the efficacy of tali-cel without consolidative allogeneic stem cell transplantation, as none of the patients underwent allo-SCT. In contrast, consolidative allo-SCT following CAR-T therapy is performed at clinician discretion in approximately 15–40% of patients in most reported series and has been associated with improved survival outcomes [18, 20, 30, 31]. Given the well-recognized risks of allo-SCT, ongoing efforts have focused on identifying patient subsets in whom transplantation may be safely omitted and durable remissions achieved with CAR-T therapy alone. The low utilization of allo-SCT in our setting therefore provided a unique opportunity to assess the standalone benefit of CAR-T therapy, with follow-up indicating durable responses with tali-cel alone.
This retrospective, multicenter study across 56 centers is subject to heterogeneity in patient selection, institutional clinical practices, depth of data capture, and lack of central response/toxicity assessment, consistent with other real-world CAR-T registries. The relatively intermediate follow-up limits assessment of long-term durability, late relapses, and delayed toxicities. Notwithstanding these limitations, the dataset represents the large real-world cohort of approved CAR-T therapy in a resource-limited setting to date, and provides meaningful, practice-informing evidence for the delivery and outcomes of tali-cel across heterogeneous healthcare environments. It provides demonstrable evidence that a centrally governed CAR-T ecosystem can deliver consistent, durable outcomes at a national scale. Tali-cel is available in India at $30,000-50,000, which is less than one-tenth the cost of commercially approved CAR-T therapies [9], and the combination of lower toxicity, reduced hospitalization, and centralized governance enhances the sustainability of this approach.
In conclusion, this centralized manufacturing–based ease-of-access model demonstrates that, with coordinated governance and shared clinical expertise, CAR-T therapies can be integrated into national cancer care pathways in resource-limited settings without compromising equity, safety, or durability—offering a replicable framework for broader global adoption.
Supplementary information
Author contributions
AK, DK, SR, HJ, MS, and RP designed the study and developed the protocol and wrote the initial draft of the manuscript. HJ, NS, DB, SM, PKB, PM, EK, SS, JPK, CN, RB, BB, LN, AS, HM, RRB, and RA were key investigators of the study. JT, HJ, AK, RP, SR, DK, and SP were involved in data analysis. JT, HJ, RP, AK, SR, and DK have assisted in study conduct, accessed, verified, and analyzed the data. SN, NJ, NNS, and TF were subject matter experts. NNS and NJ helped review and edit the manuscript. All the authors contributed to the review and approved the final version of the manuscript for submission.
Funding
This study did not receive any external funding. All study activities were conducted using internal resources and financial support provided by ImmunoACT.
Data availability
De-identified data that underlie the results reported in this Article will be made available on request to the corresponding author (purwarrahul@iitb.ac.in). Requestors need to sign a data sharing agreement. Data will be shared only after the required regulatory approvals.
Competing interests
HJ reports having received funding to the institute from ImmunoACT for conduct of the study. AK and RP are an equity holder and member of Board of Directors and advisory committee of ImmunoACT. AK and RP are patent holder for the novel humanized anti-CD19 CAR. TF received grants from NIH, Department of Defense and Leukemia Lymphoma society. TF received consulting fees from Sana Biotechnology. TF has a patent with University of Colorado Anchutz Medical Campus for CAR-T cell. TF is part of the committee for scientific affairs in American Society of Hematology. TF holds stocks in San Biotechnology. NNS receives royalties for CD22 CAR (CARGO Therapeutics). NNS is part of the scientific advisory board of ImmunoACT, CARGO and VOR. SN reports having received funding to the institute from Kite/Gilead, BMS, Allogene, Precision Biosciences, Adicet Bio, Sana Biotechnology, Cargo Therapeutics. SN has received consulting fees from Kite/Gilead, Sellas Life Sciences, Athenex, Allogene, Incyte, Adicet Bio, BMS, Bluebird Bio, Fosun Kite, Sana Biotechnology, Caribou, Astellas Pharma, Morphosys, Janssen, Chimagen, ImmunoACT, Orna Therapeutics, Takeda, Synthekine, Carsgen, Appia Bio, GlaxoSmithKline, Galapagos, ModeX Therapeutics, Jazz Pharmaceuticals. SN has received honoraria for lectures from MJH Life Sciences, PeerView, and MD. Education. SN has patents related to cell therapy and holds stocks in Longbow Immunotherapy. All the other authors declare no competing interests.
Footnotes
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A list of authors and their affiliations appears at the end of the paper.
Contributor Information
Hasmukh Jain, Email: dr.hkjain@gmail.com.
Rahul Purwar, Email: purwarrahul@iitb.ac.in.
Supplementary information
The online version contains supplementary material available at https://doi.org/10.1038/s41408-026-01569-w.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
De-identified data that underlie the results reported in this Article will be made available on request to the corresponding author (purwarrahul@iitb.ac.in). Requestors need to sign a data sharing agreement. Data will be shared only after the required regulatory approvals.