Efficacy and Safety of Tisagenlecleucel in Adult Patients With Refractory or Relapsed Follicular Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of Tisagenlecleucel in Adult Patients With Refractory or Relapsed Follicular Lymphoma (NCT03568461), a na phase 2 study. The primary outcome is Complete Response Rate (CRR) Per Independent Review Committee (IRC) Assessment.

2. Clinical Question

The study was designed to describe efficacy and safety in this clinical setting, rather than to estimate a difference between tisagenlecleucel and another treatment. Its primary outcome was complete response rate, a binary endpoint: each participant either met the complete-response definition or did not. The endpoint was based on the best overall response recorded during the specified assessment period.

Response was assessed by an independent review committee using Lugano 2014 classification response criteria. The registry describes radiological assessment using CT and PET studies. CT assessment considered anatomical measurements of index, non-index, and new lesions, as well as spleen length. PET assessment used a 5-point scale, also called the Deauville score. The listed possible response categories include complete response, partial response, stable disease, and progressive disease; PET response categories include complete metabolic response, partial metabolic response, no metabolic response, and progressive metabolic disease.

The registry record does not report the observed complete response rate or its 95% confidence interval. Consequently, it does not permit a numerical account of how many participants in the efficacy analysis set achieved the primary endpoint or how precisely that percentage was estimated.

3. Trial Design

This was a phase II, multicenter, open-label, single-arm study of tisagenlecleucel in adults with relapsed or refractory follicular lymphoma. The registry record identifies Novartis Pharmaceuticals as the sponsor. Enrollment was 98, and the study status is completed. The recorded study start was 2018-11-12, and primary completion was recorded as 2020-11-24.

All participants received tisagenlecleucel infusion; there was no randomized allocation and no comparator arm. The record identifies masking as none. These design features shape what the findings can establish: the study can describe outcomes observed after treatment in the enrolled cohort, but it cannot provide a randomized estimate of the difference between treatment and a concurrent control. Differences from another population or from outcomes under another treatment cannot be isolated from this design alone.

The primary efficacy population was the efficacy analysis set. It included patients who received tisagenlecleucel and had measurable disease at baseline according to the independent review committee. The registry defines non-measurable baseline disease as absence of an index lesion at baseline evaluation, described as no disease at baseline. This definition means the primary efficacy population is specified by both treatment receipt and baseline evaluability; it should not automatically be equated with total enrollment.

Safety counts use a denominator of 97 participants at risk, while total enrollment is 98. The registry does not explain the difference between these counts. It also does not report a sample-size justification, detailed statistical analysis plan, or explanation of how any participants with missing or unevaluable response assessments were handled. Those details should not be inferred from the phase or the single-arm design.

The registry lists 22 outcome measures and 0 analyses. It names secondary outcomes including overall response rate, duration of response, progression-free survival, overall survival, and measures of transgene concentration and cellular kinetics. Numerical results for those outcomes are not included in the registry record for interpretation; their listing alone does not establish their estimates or precision.

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: During the Screening phase and prior to enrolment into the study, participants' white blood cells were collected via leukapheresis.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Efficacy analysis set (EAS): All the patients who received tisagenlecleucel, and had measurable disease at baseline per IRC. Non-measurable disease at baseline is defined as absence of index lesion at baseline disease evaluation (i.e. no disease at baseline).

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: Enrolled Set: All the patients who were enrolled in this study. Enrollment is defined as the point at which the patient meets all inclusion/exclusion criteria, and the patients' leukapheresis product was received and accepted by the manufacturing facility.

6. Primary Endpoint

The registry lists the primary outcome as Complete Response Rate (CRR) Per Independent Review Committee (IRC) Assessment, measured over 1 year.

The primary endpoint is complete response rate as assessed by an independent review committee. It is defined as the percentage of participants whose best overall response was complete response, recorded from tisagenlecleucel infusion until progressive disease or the start of new anticancer therapy, whichever came first. The registry labels the timeframe as 1 year.

This is a binary participant-level outcome. A participant contributes to the complete response count if the qualifying best overall response is complete response; the rate expresses that count as a percentage of the specified efficacy analysis set. The registry defines that set as patients who received infusion and had measurable disease at baseline per the independent review committee. The endpoint definition therefore depends on both response classification and the analysis-population criteria.

Using an independent review committee provides a response assessment distinct from the treatment center's own evaluation. This is relevant in an open-label study, where participants and clinicians know the treatment being given. The committee applied Lugano 2014 criteria, drawing on CT and PET assessments as described in the registry record.

A complete response rate is useful for summarizing the proportion meeting a defined response category, but it does not by itself describe how long a response lasts, whether disease later progresses, or survival. Those are distinct outcomes, some of which are listed among the study's secondary measures. The registry record does not report the primary rate or its 95% confidence interval, so the observed frequency and precision cannot be described numerically.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

A complete response rate is a proportion expressed as a percentage. In general, a participant-level binary outcome is summarized by counting participants who meet the outcome definition and relating that count to the relevant analysis population. The registry specifies the outcome and population but does not report the count, denominator, or percentage for the primary endpoint. The rate therefore cannot be reconstructed from the information in the registry record.

What does the confidence interval describe?

The primary endpoint lists a 95% confidence interval as its dispersion measure. In general, a confidence interval conveys statistical uncertainty around an estimate: it reflects how much the estimate may vary because the study observes a sample rather than every person in the broader population of interest. It is not a guarantee that a particular interval contains the true value, nor does it resolve limitations arising from study design or participant selection.

For this endpoint, the confidence interval would be interpreted alongside the observed complete response percentage. A narrow interval would indicate greater statistical precision than a wide interval, given the method and assumptions used. Neither the point estimate nor the interval limits are reported in the registry record, so its width and implications cannot be evaluated. The specific interval calculation method is also not reported in the registry record.

How is response classified?

The independent review committee assessed response using Lugano 2014 classification response criteria. The registry says radiological response was first obtained from CT and PET studies. CT response drew on anatomical measurements of index, non-index, and new lesions, and spleen length. PET response used a 5-point scale, or Deauville score. The response categories listed for the overall assessment are complete response, partial response, stable disease, and progressive disease. PET categories are complete metabolic response, partial metabolic response, no metabolic response, and progressive metabolic disease.

These classifications make the endpoint operational: a response must meet the stated complete-response category rather than a broader definition of improvement. The record does not give further detail about adjudication procedures, reviewer agreement, or how conflicting assessments were resolved. Such procedures are not reported in the registry record and should not be assumed.

Why does the analysis population matter?

The primary endpoint population is the efficacy analysis set: patients who received tisagenlecleucel and had measurable disease at baseline per the independent review committee. The record defines non-measurable baseline disease as absence of an index lesion at baseline evaluation, described as no disease at baseline. Restricting the primary analysis to this set distinguishes it from total enrollment and from the safety population. The number of participants in the efficacy set is not reported in the registry record.

In general, the population definition affects the meaning of a percentage: the result describes the participants included in its denominator. If patients are excluded because baseline disease is not measurable, the endpoint estimate pertains to the defined measurable-disease efficacy set, not automatically to everyone enrolled. The record does not report a participant flow or explain missing and unevaluable response data, so the effect of these issues on the endpoint cannot be assessed.

What can the design and planning assumptions tell us?

The actual study was single-arm and open-label, with all participants who received the infusion assigned to the CTL019 group description. There was no allocation to a control treatment. General sample-size illustrations use assumptions stated as a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event outcomes, the illustrations refer to total events using the Schoenfeld method; for other outcomes, they refer to participants per arm.

Those assumptions describe planning illustrations, not the trial's observed design. In particular, equal allocation between two arms is not the design of this single-group study. Any sample sizes from such illustrations are planning quantities, not observed power, and they cannot be interpreted as evidence that the study had a particular probability of detecting an effect. The registry does not report a sample-size justification for the trial. Numerical planning outputs and the observed effect needed to interpret them are not reported in the registry record details.

More generally, statistical methods can quantify uncertainty around a measured outcome, but they cannot create a control group or eliminate possible differences between participants who receive a treatment and people in other settings. With no randomized comparison, the primary endpoint remains descriptive of the study cohort. The registry record does not report additional adjustment methods, interim-analysis procedures, or a complete statistical analysis plan.

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("CTL019")
n      <- c(94)
events <- c(64)
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  CTL019  94  64  68.1  57.7  77.3  58.1  76.6  58.1  76.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 22 outcome measures, including the primary complete response rate and secondary measures such as overall response rate, duration of response, progression-free survival, overall survival, and cellular kinetic outcomes. It lists 0 analyses. The listing of multiple outcomes raises a general multiplicity issue: when many outcomes are examined, the chance of obtaining at least one apparently notable result can increase if each is interpreted without accounting for the others. Whether and how that issue was addressed is not reported in the registry record.

No multiplicity adjustment, hierarchy of testing, or distinction between confirmatory and exploratory analyses is reported in the registry record. The statistical analysis plan is not reported in the registry record, so the planned handling of multiple endpoints cannot be inferred from the outcome list. Because numerical results for the outcomes are not reported in the registry record, there is also no basis for describing which endpoints were statistically tested or how any tests were interpreted.

Missing-data handling is not reported in the registry record. The primary population requires treatment receipt and measurable baseline disease, but the record does not state how missing response assessments, unevaluable scans, discontinuations, or other incomplete data were handled in the primary endpoint analysis. It does not report a sensitivity analysis for such data either. These details matter because a percentage can depend on which participants are counted and how unobserved outcomes are treated.

The registry defines the efficacy analysis set and separately reports safety counts for 97 participants at risk, compared with enrollment of 98. The reason for the differing counts is not reported in the registry record. The efficacy-set size is also not reported. Thus, the primary endpoint denominator and the relationship between enrolled, efficacy, and safety populations cannot be established from the available record.

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 (19.6%), pneumonia (15.5%), febrile neutropenia (8.2%), covid-19 (4.1%), pyrexia (3.1%).

The registry reports 97 participants at risk for the adverse-event summaries. It records 52 participants affected by serious adverse events and 95 affected by other adverse events. It also lists 22 deaths. The registry entries do not provide the timing, causes, or attribution of those deaths, so they should not be interpreted as treatment-related or unrelated on this information alone. The reason the safety denominator is 97 when enrollment is 98 is not reported in the registry record.

The listed serious adverse-event terms and percentages are cytokine release syndrome, 19.6%; pneumonia, 15.5%; febrile neutropenia, 8.2%; COVID-19, 4.1%; pyrexia, 3.1%; and neutropenia, 2.1%. These are registry-listed percentages for the named terms. The registry entries do not specify further details about event timing, severity grades, duration, overlap between terms, or attribution. The percentages should not be added together: a participant may be represented under more than one event term, and the record does not establish mutually exclusive categories.

Serious adverse events and other adverse events are different summaries, and the affected-participant counts do not describe the number of individual events. These safety data describe events recorded in the treated cohort; with no control group, they do not quantify an excess risk relative to another treatment or background rate. They also do not, by themselves, establish causation.

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

The study's primary question concerns the proportion of the defined efficacy population who achieved a complete response under independent review committee assessment. The registry record specifies the endpoint criteria and timeframe, but does not report the numerical complete response rate or 95% confidence interval. It is therefore not possible to state the observed frequency, compare it with a threshold, or characterize its precision from the available record.

Even if a response percentage were available, a single-arm estimate would describe the participants studied rather than quantify a causal difference from another treatment. There was no concurrent comparator and no random allocation. The study's open-label design also means treatment was not masked, although the primary response assessment was assigned to an independent review committee. These design features should inform interpretation without replacing the missing numerical result.

The primary endpoint is not interchangeable with overall response rate, duration of response, progression-free survival, or overall survival. Complete response rate addresses whether a participant's best recorded response met a specific category. Duration and time-to-event outcomes address different questions. The registry lists several such secondary measures, but their numerical estimates are not reported in the registry record.

The safety counts and listed adverse-event percentages provide descriptive information about events recorded among participants at risk. They do not establish whether an event was caused by treatment, and no comparison group is available to estimate comparative safety. The registry also does not explain why the safety denominator differs from total enrollment or provide further details about event timing and attribution.

In general, statistical significance, clinical importance, and precision are distinct concepts. A confidence interval can help assess precision, while study design and outcome definition affect what conclusions an estimate can support. Since the primary estimate and interval are not reported in the registry record, none of these features can be evaluated numerically for the primary outcome. No treatment recommendation or efficacy conclusion follows from the endpoint definition alone.

14. Why This Trial Matters Statistically

This trial is statistically notable for the way its design and endpoint define the scope of inference. It is a phase II, single-arm, open-label study, so the primary outcome is a cohort-level response percentage rather than a randomized treatment contrast. That distinction is central when readers interpret any result: a single-group estimate can describe what was observed in the study population, but it cannot by itself separate treatment effects from other influences or establish what would have occurred under a comparator.

The endpoint also makes the analysis population important. The efficacy analysis set includes patients who received infusion and had measurable disease at baseline according to the independent review committee. The total enrollment of 98 is not necessarily the denominator for this analysis, and the record does not give the efficacy-set size. The separate safety denominator of 97 makes clear that population counts need to be read according to their definitions rather than assumed interchangeable.

Independent review committee assessment is a defined part of the primary outcome process in an open-label study. The registry specifies CT and PET assessment and the response categories used, helping readers understand what a complete response represents within the study. Yet the statistical meaning of the endpoint still depends on the unreported estimate, interval, and handling of unavailable assessments.

The registry lists a broad set of outcomes, while the analysis count is 0 and the statistical plan is not reported. That gap matters because multiple endpoints can raise questions about testing strategy and interpretation. Without analysis details and numerical outcome results, the outcome list is evidence of planned or registered measurement domains, not evidence of findings.

The trial therefore illustrates why design, denominator, response definition, and reporting completeness must be considered together. The record offers substantial detail about the question and measurement framework, but not the numerical primary result needed to judge its observed level or precision.

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 most immediate limitation for interpreting the registry record is the absence of the primary complete response rate and its 95% confidence interval. Without those results, the observed primary outcome and its statistical precision cannot be described. The registry also does not report the efficacy analysis-set size, the number of participants with classifiable responses, or a participant flow explaining how enrollment relates to analysis populations.

The study is single-arm, with no random allocation or control group. This prevents a direct randomized comparison and limits conclusions to description of the treated cohort. The open-label design is recorded, and although response was assessed by an independent review committee, details about assessment procedures beyond the stated criteria are not reported in the registry record.

Important analytical details are missing. The statistical analysis plan, sample-size justification, multiplicity strategy, and missing-data methods are not reported in the registry record. Nor are interim-analysis procedures or additional adjustment methods. The absence of these details means readers cannot determine whether analyses followed prespecified plans or how incomplete assessments may have affected the endpoint.

The safety record uses 97 participants at risk, compared with enrollment of 98, but the reason for the difference is not reported. The registry entries include counts for participants affected by serious and other adverse events, listed serious adverse-event percentages, and 22 deaths, but do not provide event timing, causes, or attribution. Consequently, the safety summaries cannot establish causation or comparative risk.

Finally, the registry lists multiple secondary outcomes, but their numerical estimates are not reported in the registry record. The outcomes' names alone do not support conclusions about response duration, survival, or cellular kinetics. These limitations are specific to the information and design recorded, not evidence that an unreported result was favorable or unfavorable.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Efficacy and Safety of Tisagenlecleucel in Adult Patients With Refractory or Relapsed Follicular Lymphoma — NCT03568461.
• Registry record last updated 2026-07-09; status last verified 2026-07.
• Results first posted 2022-07-22.
• 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

NCT03568461 is a completed phase II, multicenter, open-label, single-arm study sponsored by Novartis Pharmaceuticals. It enrolled 98 adults with relapsed or refractory follicular lymphoma and evaluated tisagenlecleucel. The recorded study start was 2018-11-12, with primary completion on 2020-11-24.

The primary endpoint was complete response rate per independent review committee assessment, with a registry timeframe of 1 year. The efficacy analysis set comprised participants who received infusion and had measurable baseline disease per the committee. The numerical primary result and 95% confidence interval are not reported in the registry record.

The registry lists 22 outcome measures and 0 analyses. Safety summaries report 97 participants at risk, 52 affected by serious adverse events, 95 affected by other adverse events, and 22 deaths. The record does not provide a randomized comparison or explain the difference between enrollment and the safety denominator.