Lisocabtagene Maraleucel (JCAR017) as Second-Line Therapy (TRANSCEND-PILOT-017006): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Lisocabtagene Maraleucel (JCAR017) as Second-Line Therapy (TRANSCEND-PILOT-017006) (NCT03483103), a na phase 2 study. The primary outcome is Overall Response Rate (ORR).

2. Clinical Question

3. Trial Design

This is a phase 2, open-label, multicenter, single-group study of lisocabtagene maraleucel as second-line therapy. The registry lists an enrollment of 74 and a completed study status. The recorded study dates are 2018-07-27 for the start and 2021-09-24 for primary completion.

Eligible participants were adults with aggressive B-cell non-Hodgkin lymphoma who had relapsed after, or were refractory to, a single line of immunochemotherapy and were ineligible for hematopoietic stem cell transplant based on age, performance status, and/or comorbidities. The primary endpoint population is described as participants with PET-positive disease who received at least one infusion of JCAR017. This definition is narrower than the general eligibility description, so the number included in the primary endpoint analysis cannot be assumed to equal the enrollment count.

Participants received a single intravenous dose of lisocabtagene maraleucel on Day 1, between 2 and 7 days after completing lymphodepleting chemotherapy. The study description says participants would be followed for 2 years for safety, pharmacokinetics and biomarkers, disease status, quality of life, and survival. The primary endpoint timeframe is described as extending from first dose until disease progression, end of study, the start of another anticancer therapy, or hematopoietic stem cell transplantation, up to approximately 24 months.

Because the study has no separate control arm, its design can describe responses and safety outcomes among treated participants but cannot provide a randomized estimate of the difference between this treatment and another intervention. The registry record does not report further details of the protocol or the rationale for the enrollment target.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: All efficacy and safety analyses were conducted on the JCAR017-treated Analysis Set.

Pre-Treatment Phase

Reasons for not completing this period:

Treatment Phase

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants with PET positive disease who received at least one infusion of JCAR017

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: 74 participants were leukapheresed.

6. Primary Endpoint

The registry lists the primary outcome as Overall Response Rate (ORR), measured over From first dose to disease progression, end of study, the start of another anticancer therapy, or hematopoietic stem cell transplantation (up to approximately 24 months).

The primary endpoint is overall response rate, expressed as the percentage of participants whose best overall response was complete response or partial response. Responses were assessed by an Independent Review Committee using the study’s PET-based criteria. Complete response includes PET 5-point scale scores of 1, 2, or 3, with or without a residual mass. Partial response is described as a score of 4 or 5b with reduced uptake compared with baseline and residual mass or masses of any size.

Overall response rate is used to summarize whether participants experienced a qualifying tumor response during the specified assessment period. Combining complete and partial responses produces a single percentage, while the response categories retain distinctions in the underlying assessment. The registry describes the endpoint as applying from first dose until disease progression, end of study, the start of another anticancer therapy, or hematopoietic stem cell transplantation, up to approximately 24 months.

The registry lists a 95% confidence interval as the endpoint’s measure of precision. A confidence interval conveys uncertainty around an estimated response percentage; it does not establish that a response was caused by treatment. Neither the overall response estimate nor the interval limits are reported in the registry record, so the magnitude and precision of the primary result cannot be evaluated from that record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a confidence interval communicate?

In general, a confidence interval expresses the statistical uncertainty around an estimate. For a percentage such as overall response rate, the point estimate describes the observed proportion in the analyzed population, while the interval gives a range of values compatible with the data under the method used. A narrower interval generally indicates greater precision, and a wider interval indicates more uncertainty. An interval does not correct limitations in study design, represent the range of outcomes for individual participants, or establish that an observed response was caused by treatment.

The registry lists a 95% confidence interval for overall response rate, but does not give the response percentage or interval limits. The method used to calculate that interval is not reported in the registry record. Without the estimate, interval, and endpoint denominator, the precision of the primary finding cannot be assessed.

How should a single-group result be interpreted?

In general, a single-group study estimates outcomes among participants who received the study intervention. It can describe the observed response frequency and adverse events in that group. A randomized comparison is designed to support a direct comparison between groups by assigning participants to different interventions under a defined allocation process. This trial is listed as single group, with allocation not applicable, so it does not supply such a comparison.

That distinction matters because outcomes can be influenced by factors beyond the intervention, including participant characteristics, disease course, and other care. A response proportion from a single group is therefore descriptive of the analyzed participants and study conditions. It should not be treated as a treatment-versus-control effect or as proof of causation.

What does the endpoint definition contribute?

The endpoint is based on the best overall response, with complete response or partial response counting toward overall response rate. The registry specifies that an Independent Review Committee assessed response using PET-based criteria. It describes complete response using scores 1, 2, or 3 on the PET 5-point scale, with or without a residual mass; partial response requires score 4 or 5b, reduced uptake compared with baseline, and residual mass or masses of any size.

In general, prespecified response rules make an endpoint more reproducible by defining how observations are classified. Independent assessment can reduce reliance on the treating team’s judgment, although the registry does not report further details of assessment procedures, adjudication, or reviewer blinding. Masking is listed as none, and the study is open label.

Why can event rates vary in a clinical study?

In general, a proportion is affected by the number of participants observed and by how events are defined and collected. When the analyzed population is small, each participant’s outcome can have a noticeable influence on the estimated percentage. For adverse events, counts also depend on follow-up duration, reporting rules, and whether repeated events in one participant are counted once or multiple times. The registry gives participant counts for the adverse-event group but does not report all details of event counting or exposure duration.

Over-dispersion is a general statistical concern when observed variability exceeds what a simple probability model assumes. It can arise when participants have differing underlying risks or observations are clustered. When present, a model that assumes less variability may give intervals that are too narrow. The registry entries do not identify a model for the primary endpoint or indicate whether over-dispersion was assessed, so no claim can be made that it was relevant to or addressed in this analysis.

What is not available about the analysis?

The registry describes the endpoint population and the response criteria, but it does not report the primary result, the endpoint denominator, the confidence interval limits, or the method used to construct that interval. The statistical analysis plan, treatment of missing response assessments, and handling of participants who began another anticancer therapy or underwent transplantation are not reported in the registry record.

In general, interpretation of a percentage depends on knowing who was included in its denominator and how incomplete outcome data were handled. Different analysis populations or rules for missing assessments can change the meaning of the reported estimate. Since these details and the estimate itself are absent, the primary analysis cannot be independently assessed from the registry information.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Lisocabtagene Maraleucel (JCAR017)")
n      <- c(61)
events <- c(49)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Lisocabtagene Maraleucel (JCAR017)  61  49  80.3  68.2  89.4  68.7  88.4  68.6  88.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 37 outcome measures and one analysis. It identifies overall response rate as the primary endpoint, while the listed secondary outcomes include treatment-emergent adverse events, laboratory changes, and complete response rate. The statistical plan for controlling the chance of false-positive findings across multiple outcomes is not reported in the registry record. The existence of multiple outcomes does not by itself establish that a multiplicity adjustment was or was not used.

The primary endpoint population is defined as participants with PET-positive disease who received at least one infusion. The registry does not give the number of participants in that population, the number with evaluable response assessments, or the handling of participants whose response data were missing. It also does not report whether missing assessments were treated as nonresponses, excluded, or addressed using another method.

The endpoint timeframe can include disease progression, end of study, the start of another anticancer therapy, or hematopoietic stem cell transplantation. How these events were handled in the primary analysis is not reported in the registry record. The registry also does not provide details on the analysis populations used for safety or other outcomes, or on how departures from the stated follow-up plan were addressed.

In general, missing outcome data can affect a response estimate when the likelihood of missingness is related to participants’ outcomes or clinical status. Clear reporting of denominators, missing-data rules, analysis populations, and multiplicity procedures helps readers judge how much confidence to place in statistical findings. Those details are not available in the registry record, and the primary response estimate itself is also not reported.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cytokine release syndrome (13.1%), confusional state (4.9%), upper gastrointestinal haemorrhage (3.3%), muscular weakness (3.3%), pulmonary embolism (3.3%).

The registry lists safety information for the lisocabtagene maraleucel group. It records 20 participants with serious adverse events among 61 at risk, and 59 participants with other adverse events among 61 at risk. These are participant counts, not a comparison with another treatment group. The record also lists 30 deaths, without stating in the registry entries whether they were considered related to treatment or describing their causes or timing.

The serious adverse-event terms with reported percentages are cytokine release syndrome at 13.1%, confusional state at 4.9%, upper gastrointestinal haemorrhage at 3.3%, muscular weakness at 3.3%, pulmonary embolism at 3.3%, and febrile neutropenia at 1.6%. These percentages describe the listed terms in this study group. The registry information does not establish whether participants could contribute to more than one term, nor does it provide a comparative rate.

In general, adverse-event findings depend on definitions, collection procedures, and observation time. The registry describes planned follow-up but does not specify the relevant exposure time for each listed safety figure. The counts should therefore be read as reported study-group observations, not as estimates of comparative risk or proof that the intervention caused an event.

13. What the Result Does, and Does Not, Mean

The registry record documents a phase 2, open-label, single-group study of lisocabtagene maraleucel for adults with aggressive B-cell non-Hodgkin lymphoma who had relapsed after, or were refractory to, a single line of immunochemotherapy and were ineligible for hematopoietic stem cell transplant. Its primary endpoint is overall response rate among participants with PET-positive disease who received at least one infusion, based on Independent Review Committee assessment.

The record does not report the overall response percentage or its 95% confidence interval. It therefore does not establish the observed response frequency or the precision of that estimate. The enrollment of 74 is not a substitute for the primary endpoint result or its analysis denominator, which is not reported in the registry record.

The study’s single-group design also limits what can be inferred. In general, an observed outcome in a treated group does not show how the same population would have fared under another treatment or without the intervention. There is no randomized comparator in this study to support a direct estimate of relative effect.

The safety data record participants with serious and other adverse events, selected serious-event terms and their percentages, and 30 deaths. Those observations characterize the group as recorded, but the registry entries do not attribute deaths or adverse events to treatment. They also do not establish how rates compare with another care option.

Accordingly, the registry information supports a description of the study design, response criteria, and selected safety counts. It does not support a conclusion about the magnitude of the primary response result, its statistical precision, or comparative benefit and harm. Those aspects are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically notable for studying an explicitly defined response endpoint in a single-group setting. The primary outcome combines complete and partial responses, assessed using PET criteria by an Independent Review Committee. Its definition and target population are important for understanding what an eventual response percentage would represent.

The single-group design also makes the distinction between describing outcomes and estimating comparative effects especially important. A response rate can summarize observed outcomes among the eligible treated participants, but it cannot by itself quantify how outcomes differ from those under another treatment. The registry lists no comparator arm, so comparative claims cannot be drawn from this design alone.

Precision is another central issue. The registry specifies a 95% confidence interval for the primary endpoint, but the response estimate, interval limits, and endpoint denominator are not reported in the registry record. Without them, readers cannot assess the observed frequency or its uncertainty. The enrollment count does not resolve that gap because the stated primary population has additional eligibility conditions and its size is not given.

The safety information similarly requires careful interpretation. It includes counts among participants at risk, percentages for selected serious-event terms, and a death count, but no like-for-like control group. These data can describe reported events in the study group; they cannot establish comparative safety or causal attribution.

More generally, this record illustrates how endpoint definitions and study structure shape statistical interpretation. The response criteria, analysis population, missing-data approach, and confidence interval method all affect how an estimate should be understood. Several of those analysis details, along with the primary result, are not reported in the registry record.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main trial-specific limitation in the registry information is the absence of the primary endpoint result. Although overall response rate and a 95% confidence interval are specified, neither the estimate nor its interval limits are reported in the registry record. The endpoint denominator is also unavailable, preventing assessment of how many participants contributed to that result.

The study is listed as open label and single group, with no randomized comparator. This means the registry record cannot support a direct estimate of the difference in response or safety outcomes between lisocabtagene maraleucel and another intervention. The recorded enrollment of 74 does not indicate the size of the primary endpoint population, which is restricted to participants with PET-positive disease who received at least one infusion.

Several analysis details are not reported in the registry record: the confidence interval method, handling of missing response assessments, treatment of disease progression or subsequent therapy in the endpoint analysis, and the statistical plan for multiple outcomes. The record lists 37 outcome measures, but does not describe any multiplicity procedure. These omissions constrain assessment of the primary analysis and secondary findings.

The safety group lists participant counts and selected serious-event percentages, but the registry entries do not state the causes or timing of the 30 deaths or whether they were considered related to treatment. Comparative safety is not estimable from a single-group record. Event ascertainment details and exposure duration for the safety figures are also not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Lisocabtagene Maraleucel (JCAR017) as Second-Line Therapy (TRANSCEND-PILOT-017006) — NCT03483103.
• Registry record last updated 2023-12-20; status last verified 2023-11.
• Results first posted 2022-12-29.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry describes a completed phase 2, open-label, multicenter, single-group study of lisocabtagene maraleucel as second-line therapy for adults with aggressive B-cell non-Hodgkin lymphoma who were ineligible for hematopoietic stem cell transplant. Enrollment is listed as 74. The study began on 2018-07-27, with primary completion on 2021-09-24.

The primary endpoint is overall response rate among participants with PET-positive disease who received at least one infusion, assessed by an Independent Review Committee. The registry lists a 95% confidence interval, but the response estimate, interval limits, and endpoint denominator are not reported in the registry record. Safety information includes 20 participants with serious adverse events and 59 with other adverse events, each among 61 at risk, and a listed death count of 30.

The single-group design does not provide a randomized comparison. The registry record does not report several analysis details, including missing-data handling and the method used for the primary confidence interval.