Multinational Clinical Study Comparing Isatuximab, Carfilzomib And Dexamethasone To Carfilzomib And Dexamethasone In Relapse And/Or Refractory Multiple Myeloma Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Multinational Clinical Study Comparing Isatuximab, Carfilzomib And Dexamethasone To Carfilzomib And Dexamethasone In Relapse And/Or Refractory Multiple Myeloma Patients (NCT03275285), a randomized phase 3 study. The primary outcome is Progression Free Survival (PFS) As Determined by Independent Response Committee (IRC): Primary Analysis.

2. Clinical Question

The trial was randomized and parallel-group, with 302 participants enrolled. Its official title describes it as open label, while the registry’s masking field is listed as single; the record does not clarify that distinction. The main result is a time-to-event comparison, so it concerns the relative timing of disease progression or death rather than a simple comparison of response percentages.

3. Trial Design

This was a randomized, phase 3, multicenter study sponsored by Sanofi. It compared two parallel treatment groups: isatuximab with carfilzomib and dexamethasone (IKd), and carfilzomib with dexamethasone (Kd). The registry records 302 participants enrolled, with 179 in the IKd group and 123 in the Kd group for the primary analysis. The condition is listed as plasma cell myeloma, and the official title describes participants with relapse and/or refractory multiple myeloma previously treated with 1 to 3 prior lines.

The study started on 2017-10-25, had a primary completion date of 2022-01-14, and is listed as completed. The primary outcome timeframe ends at the primary analysis data cut-off date of 7 Feb 2020; the median duration of follow-up for that analysis was 20.73 months. These dates describe distinct parts of the record: the study’s listed completion date does not change the stated cut-off for the primary analysis.

The treatment schedules used 28 day cycles. In the IKd group, isatuximab was administered intravenously on days 1, 8, 15 and 22 of the first cycle, then on days 1 and 15 of later cycles. Carfilzomib was given on days 1, 2, 8, 9, 15 and 16, and dexamethasone on days 1, 2, 8, 9, 15, 16, 22 and 23. In the Kd group, the carfilzomib and dexamethasone schedules were the same. Dexamethasone could be administered intravenously or by mouth.

The official title calls the study open label, whereas the registry’s masking field says single. What was masked, and how masking was implemented, is not reported in the registry record. Other details of conduct, including the original sample-size justification and any interim-analysis plan, are not reported in the registry record.

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: First result analysis (A) reported was for a data cut-off date of 7 Feb 2020 for efficacy outcomes, 14 Jan 2022 for CR, MRD and PFS2. PFS data was reported at both cut-off dates: 7 Feb 2020 \& 14 Jan 2022. Primary A of PFS refers to planned interim A conducted at 103 events (death/PD) with cut-off date 7 Feb 2020 \& Final A of PFS conducted at 159 events with cut-off date 14 Jan 2022. Data cut-off for overall survival and LPLV was 7 Feb 2023 and 3 Jan 2025, respectively.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysis was performed on Intent to Treat (ITT) population that included all participants who gave their informed consent and for whom there was a confirmation of successful allocation of a randomization number by the interactive response technology (IRT).

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: Analysis was performed on randomized population.

6. Primary Endpoint

The registry lists the primary outcome as Progression Free Survival (PFS) As Determined by Independent Response Committee (IRC): Primary Analysis, measured over From randomization until the primary analysis data cut-off date of 7 Feb 2020 (median duration of follow-up was 20.73 months).

Progression-free survival (PFS) was defined as the time from randomization to the first documentation of progressive disease or death from any cause, whichever occurred first. The registry states that progression was assessed using International Myeloma Working Group criteria. When neither progression nor death had been observed before the cut-off or the start of further anti-myeloma treatment, the observation was censored at the last valid disease assessment without progression before whichever of those events came first.

PFS is a time-to-event endpoint: it accounts for both whether the event occurred and how long participants remained without a recorded event during follow-up. It is used to describe the timing of progression or death, rather than only the proportion of participants meeting a response definition. Kaplan-Meier estimation was specified for the endpoint. This method can incorporate censored observations, while retaining the distinction between an event that was observed and a follow-up period that ended without an observed event.

The endpoint combines progression and death into a single event definition. It therefore does not separately describe the timing of progression and the timing of death. The reported analysis was based on the intent-to-treat population and used the primary analysis cut-off date of 7 Feb 2020.

7. Results Posted in the Registry

• Carfilzomib + Dexamethasone (Kd) vs Isatuximab + Carfilzomib + Dexamethasone (IKd): hazard ratio 0.53 (95% CI 0.32–0.89), reported p < 0.001 (as reported in the registry).

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Percentage of Participants With Overall Response (OR) as Determined by Independent Response Committee: Primary Analysis

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Isatuximab + Carfilzomib + Dexamethasone (IKd): 86.6% (155/179) versus 82.9% (102/123) on control; risk difference 3.7 percentage points (95% CI -4.6 to 12.0), risk ratio 1.04 (0.95–1.15); unadjusted two-proportion z-test p = 0.379.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Isatuximab + Carfilzomib + Dexamethasone (IKd) and the control. The interval gives the range of effects that remain compatible with the data.

Percentage of Participants With Very Good Partial Response (VGPR) or Better as Determined by Independent Response Committee: Primary Analysis

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Isatuximab + Carfilzomib + Dexamethasone (IKd): 72.6% (130/179) versus 56.1% (69/123) on control; risk difference 16.5 percentage points (95% CI 5.6 to 27.5), risk ratio 1.29 (1.08–1.55); unadjusted two-proportion z-test p = 0.003.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Isatuximab + Carfilzomib + Dexamethasone (IKd) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Percentage of Participants With VGPR or Better With Minimal Residual Disease (MRD) Negativity: Primary Analysis

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Isatuximab + Carfilzomib + Dexamethasone (IKd): 29.6% (53/179) versus 13.0% (16/123) on control; risk difference 16.6 percentage points (95% CI 7.7 to 25.5), risk ratio 2.28 (1.37–3.79); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Isatuximab + Carfilzomib + Dexamethasone (IKd) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The response outcomes provide information that complements, but does not replace, the primary PFS analysis. Overall response percentages are relatively close across groups, while the posted VGPR-or-better and MRD-negativity outcomes show a more separated pattern. These outcomes describe response depth and MRD status, whereas PFS describes time to progression or death. Their differences in definition mean that they need not give identical statistical signals.

The sponsor reports a Cochran-Mantel-Haenszel test for overall response. The posted results do not include sponsor-reported analyses for the other primary-analysis response outcomes described in the record. The unadjusted re-calculations for those outcomes offer a basic comparison from the displayed summary proportions, but they do not incorporate adjustment or account for the full structure of the trial analysis.

Secondary outcomes generally carry less evidential weight than the primary endpoint when many outcomes are examined. Each additional test creates another opportunity for a seemingly notable result to occur by chance. The registry lists multiple secondary outcomes and 35 secondary results as posted, but a multiplicity procedure or hierarchy for interpreting those tests is not reported in the registry record. Without such information, secondary p-values should be treated as exploratory or supportive rather than as independent confirmation of the primary finding.

The record also lists response outcomes for final analyses, overall survival, and duration of response, among other measures. The outcome names alone do not establish what their results were. The pattern across the available primary-analysis response results is therefore best understood as complementary descriptive evidence, with the primary PFS analysis remaining the central time-to-event result.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Percentage of Participants With Overall Response (OR) as Determined by Independent Response Committee: Primary Analysis
• Percentage of Participants With Very Good Partial Response (VGPR) or Better as Determined by Independent Response Committee: Primary Analysis
• Percentage of Participants With VGPR or Better With Minimal Residual Disease (MRD) Negativity: Primary Analysis
• Percentage of Participants With VGPR or Better With Minimal Residual Disease (MRD) Negativity: Final Analysis
• Percentage of Participants With Complete Response (CR) as Per Independent Response Committee: Final Analysis
• Percentage of Participants With Complete Response With MRD Negativity: Final Analysis
• Overall Survival (OS)
• Duration of Response (DOR): Primary Analysis

9. Statistical Interpretation

10. Statistical Methods Explained

The main analysis combines a survival-curve method with a comparison of event experience between randomized groups. The registry identifies the Kaplan-Meier method for estimating PFS and a stratified log-rank test for the reported hazard ratio. The endpoint is time from randomization to progression or death, with censoring at specified follow-up limits when an event has not been observed.

What does Kaplan-Meier estimation do?

As a general statistical concept, Kaplan-Meier estimation builds an estimate of the probability of remaining event-free over time. When a participant’s follow-up ends without a recorded event, that participant contributes information up to the censoring time; the record does not treat censoring as if progression or death occurred then. The registry specifies censoring when there is no observed progression or death before the analysis cut-off or initiation of further anti-myeloma treatment, using the last valid disease assessment without progression before the relevant limit.

Censoring is important because follow-up may end for reasons other than the endpoint event. The method relies on assumptions about how censoring relates to future event experience. The registry describes the censoring rules, but a fuller account of how the assumptions were assessed is not reported in the registry record. The method estimates event-free experience through the observed follow-up; it does not make later outcomes known for participants whose observations were censored.

How should a hazard ratio be read?

A hazard ratio compares the estimated event hazard between groups over follow-up. It is a relative measure and is not an absolute risk difference, a median-time difference, or a probability that an individual participant will have an event. The ordering of groups matters: the registry labels the comparison Kd versus IKd and reports a hazard ratio of 0.531. The corresponding 99% confidence interval is 0.318 to 0.889. The estimate below 1 points toward a lower event hazard for IKd relative to Kd under that comparison ordering.

The stratified log-rank test compares time-to-event experience while accounting for the trial’s stratification structure. The stratification factors themselves are not reported in the registry record. A p-value describes the compatibility of the observed test result with a specified null hypothesis under the test’s assumptions; it is not a measure of effect size or the probability that the null hypothesis is true.

What do the response analyses measure?

Overall response, very good partial response or better, and minimal residual disease negativity are reported as percentages of participants. These binary outcomes describe whether participants met a stated response category by the relevant analysis. They do not incorporate the time at which the response occurred in the same way as PFS. For these endpoints, an unadjusted risk difference describes the difference between the observed group proportions. The recalculated comparisons are simple unadjusted analyses based on posted summary statistics, whereas the sponsor’s reported overall-response test used a Cochran-Mantel-Haenszel method.

In general, adjustment can account for specified strata or other design features, while an unadjusted comparison does not. The registry does not provide a sponsor-reported test for the VGPR-or-better and MRD-negativity primary-analysis outcomes listed in the posted results. Recalculated p-values for those endpoints should therefore be read as descriptive, unadjusted comparisons rather than as substitutes for a reported adjusted analysis.

What do the planning illustrations mean?

The sample-size illustrations use a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. They consider effects set at stated fractions of the observed effect. The time-to-event illustrations are expressed as total events, using the Schoenfeld approach; the other illustrations are expressed as participants per arm. These are hypothetical planning calculations, not the trial’s original design assumptions. The original sample-size justification and the trial’s own design assumptions are not reported in the registry record.

In general, an interval estimate expresses a range of values compatible with the data and analysis method, subject to its assumptions. A test result and an interval answer related but different questions: the test evaluates a null hypothesis, while the interval conveys uncertainty about the size and direction of an estimated effect. Neither method removes uncertainty due to limited follow-up, missing assessments, or the applicability of the study population to other settings.

11. Confidence Intervals and Precision

The primary hazard-ratio estimate is 0.531, with a 99% confidence interval from 0.318 to 0.889. The entire interval lies below 1, indicating that the reported estimate and its interval point in the same relative-hazard direction. The interval remains fairly broad, so a range of effect magnitudes is compatible with the analysis; the point estimate should not be treated as exact.

A confidence interval describes uncertainty in an estimate under the analysis method and its assumptions. It is not a guarantee that the true effect lies within the interval, nor does it describe the range of outcomes for individual participants. Here, the confidence level attached to the sponsor-reported hazard ratio is 99%. The registry’s primary outcome description also refers to a 95% confidence interval for the median, but the posted Kd median has only a lower bound of 15.77 months; its upper bound is not reported in the registry record. The IKd median and its interval are not reported in the registry record.

For the secondary overall-response comparison, the unadjusted recalculated risk-difference interval spans zero. That interval therefore reflects uncertainty about the direction and size of the absolute difference in response proportions. For VGPR or better and for VGPR or better with MRD negativity, the recalculated risk-difference intervals lie above zero. Those intervals are unadjusted and do not account for possible multiplicity across the many recorded outcomes.

Precision depends on the number of observed events for a time-to-event comparison, the number of participants and outcome frequencies for response comparisons, and the analysis assumptions. The enrolled sample and follow-up period constrain how precisely effects can be estimated. The upper median-PFS confidence bound for Kd, the median PFS for IKd, and several details needed to assess the full precision of the reported results are not reported in the registry record.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning illustrations show hypothetical sample requirements for different fractions of the observed effect. For PFS, the figures are total events needed, not participants per arm. For the response outcomes, the figures are participants per arm. The calculations assume a two-sided significance level of 0.05, equal allocation between the two groups, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect.

The 80% power column represents a planning scenario in which the calculation is designed to have an 80% chance of detecting the specified effect under the assumptions, if that effect were the true one. The 90% power column uses a higher target chance of detecting that effect under the same kind of assumptions. These are design-planning concepts, not guarantees that a study will produce a statistically significant result.

Smaller effects require more information to distinguish them from random variation, so the illustrations require more events or participants when the assumed effect is reduced. The original trial design assumptions and sample-size justification are not reported in the registry record. These figures are planning illustrations based on the observed effects, not observed power; they do not indicate the probability that the completed trial’s result is true or that the treatment has a particular effect.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

d is the total number of events needed (Schoenfeld's formula) with 1:1 allocation and proportional hazards.

Worked calculation for this trial

1. Hazard ratio HR = 0.531, so ln(HR) = -0.6330.
2. d = 4 × (1.96 + 0.842)² / [ln(0.531)]² = 78.4, rounded up to 79 events in total for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
hr <- 0.531                              # observed hazard ratio
events_needed <- function(power, frac = 1) ceiling(round(4 * (z_a + qnorm(power))^2 / log(hr^frac)^2, 6))   # Schoenfeld, 1:1 allocation
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: events = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(events_needed(0.80, f), big.mark = ","), format(events_needed(0.90, f), big.mark = ",")))

# Simulation: given d total events under proportional hazards, events in the treatment arm are Binomial(d, hr / (1 + hr)).
# The score (log-rank type) statistic is (D1 - d / 2) / sqrt(d / 4).
set.seed(3275285)
d    <- events_needed(0.80)
reps <- 20000
D1 <- rbinom(reps, d, hr / (1 + hr))
z  <- (D1 - d / 2) / sqrt(d / 4)
cat(sprintf("Simulated power with %s events: %.3f (%d replicates)\n", format(d, big.mark = ","), mean(abs(z) > z_a), reps))

Output from running the code

100% of observed effect: events = 79 (80% power), 105 (90% power)
 75% of observed effect: events = 140 (80% power), 187 (90% power)
 50% of observed effect: events = 314 (80% power), 420 (90% power)
Simulated power with 79 events: 0.767 (20000 replicates)

The simulation uses the fact that, with d events in total and proportional hazards, the number of events in the treatment arm is binomial. It is an approximation that conditions on the total number of events, and it should land close to the target power.

14. Analyses Reported by the Sponsor

The primary PFS comparison is the sponsor-reported stratified log-rank analysis. Its hazard ratio is 0.531, with a 99% confidence interval of 0.318 to 0.889 and p < 0.001. The time-to-event result uses the sponsor’s reported hazard ratio; a separate unadjusted re-calculation is not used for this endpoint. The registry does not flag a discrepancy between the posted results and the analysis used for the primary comparison.

For overall response, the sponsor reports a Cochran-Mantel-Haenszel test, while the unadjusted re-calculation is based on the posted response proportions. Because the methods differ, the sponsor’s own test is the appropriate sponsor-reported analysis to cite; the unadjusted calculation is a separate descriptive check. The registry does not report sponsor analyses for the posted VGPR-or-better and MRD-negativity primary-analysis outcomes.

Recalculated comparisons are not replacements for sponsor analyses or for a complete individual-participant analysis. They use posted summary statistics and do not reproduce stratification or any other adjustment not available from those summaries. Where sponsor analyses are reported, interpretation should distinguish the sponsor’s analysis from a simple unadjusted calculation rather than merging their estimates or p-values.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists a range of outcome measures, including PFS, several response categories, MRD outcomes, overall survival, and duration of response. Testing multiple outcomes increases the chance that at least one result will appear notable by chance, even if there is no underlying effect for any particular outcome. Statistical approaches such as a prespecified hierarchy or adjustment can address that issue, but a multiplicity strategy is not reported in the registry record. The interpretation of secondary p-values must therefore remain cautious.

The primary population is described as intent to treat and includes participants who consented and had successful confirmation of a randomization number through the interactive response technology system. The population used for each secondary analysis is not reported in the registry record. The record identifies PFS censoring rules, including censoring in relation to the last valid disease assessment, the analysis cut-off, and initiation of further anti-myeloma treatment. Other missing-data procedures are not reported in the registry record.

The registry does not report the trial’s original sample-size assumptions, a sample-size justification, or an interim-analysis plan. It also does not state a complete statistical-analysis plan for all outcomes or describe how the stratification factors were selected. These omissions limit the ability to determine from the registry record alone how all planned analyses were specified before results were observed.

Some endpoint details are incomplete in the posted results: the IKd median PFS is not reported, and the reported Kd median has no upper confidence bound. The study’s official title says open label, whereas the masking field lists single; the record does not explain the masking arrangement. These are reporting limitations, not proof that analyses or procedures were absent.

16. 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: pneumonia (23.2%), lower respiratory tract infection (4.9%), influenza (4.1%), acute kidney injury (4.1%), upper respiratory tract infection (3.4%).

The registry reports serious adverse events and other adverse events using counts of participants affected and counts at risk. Serious adverse events were recorded for 74 of 122 participants at risk in the Kd group and 129 of 177 at risk in the IKd group. Other adverse events were recorded for 113 of 122 participants at risk in Kd and 167 of 177 at risk in IKd. The record also lists 59 deaths in Kd and 83 in IKd. These are descriptive counts; they do not establish that a treatment caused an event or a death.

The leading serious adverse-event terms listed include Pneumonia at 23.2%, Lower Respiratory Tract Infection at 4.9%, Influenza at 4.1%, Acute Kidney Injury at 4.1%, Upper Respiratory Tract Infection at 3.4%, and Cardiac Failure at 3.3%. The listed terms are not assigned to a specific treatment group in the record excerpt, so they should not be read as group-specific rates. The registry information does not provide enough context to compare event timing, severity distributions, or causal attribution between groups.

Safety counts should be interpreted alongside the denominators and the study’s follow-up and reporting definitions. They are not a substitute for an adjusted safety analysis or a complete description of individual cases. Additional details about how these events were assessed are not reported in the registry record.

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

The posted primary analysis estimates a difference in time-to-event experience between the randomized groups. The sponsor-reported hazard ratio and its 99% confidence interval point toward a lower PFS event hazard for IKd relative to Kd under the stated comparison ordering. The analysis is based on the defined intent-to-treat population and follow-up through the primary analysis cut-off date. This is evidence about the comparison made in this study, not a prediction of what will happen to a particular person.

The result does not supply a complete comparison of median PFS times: the Kd median is reported as 19.15 months with a lower confidence bound of 15.77 months, while the IKd median and the upper Kd bound are not reported in the registry record. The hazard ratio should not be converted into a number of months or a percentage change in survival. Those would require different information or calculations not reported as the sponsor’s primary result.

Response outcomes add context about whether participants met response definitions, but they do not answer the same question as PFS. The secondary results also involve multiple outcomes, and a strategy for controlling multiplicity is not reported in the registry record. Their interpretation is therefore less definitive than that of a prespecified primary endpoint with a reported sponsor analysis.

Statistical evidence does not by itself establish the clinical importance of an effect, explain every potential benefit or harm, or show how well findings apply outside the studied population. The registry record concerns participants with relapse and/or refractory multiple myeloma previously treated with 1 to 3 prior lines. It does not report enough information to assess every population or circumstance to which the findings might be applied. No individual treatment decision follows from these statistical results alone.

18. Why This Trial Matters Statistically

This trial illustrates how a randomized comparison can use a time-to-event endpoint to evaluate more than response status at a single assessment. PFS incorporates the timing of documented progression or death and uses censoring rules for participants without an observed event by the relevant follow-up limit. That structure makes the endpoint informative about event timing, while also making its interpretation dependent on follow-up and censoring.

The result also shows why the order of groups in a hazard ratio matters. The registry labels the comparison Kd versus IKd, so interpretation must account for that ordering before describing which group has the lower estimated hazard. Reporting the confidence interval alongside the point estimate makes the uncertainty and direction of the comparison clearer than the point estimate alone.

For clinical researchers, the record is a useful example of keeping the primary time-to-event analysis distinct from response percentages and unadjusted re-calculations. Different endpoints address different questions, and a sponsor-reported stratified analysis should not be conflated with a simple comparison of summary proportions. Secondary outcomes can enrich interpretation, but many outcome tests raise multiplicity concerns when no testing strategy is reported.

The record also demonstrates the limits of registry-level interpretation. The sponsor-reported PFS comparison is available, but complete arm-specific median information, the original design assumptions, and several analysis details are not. Clear separation of reported results, unadjusted calculations, and unreported methods is essential for a calibrated statistical reading.

19. 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.

Several trial-specific gaps constrain interpretation. Although the primary result reports a hazard ratio and a 99% confidence interval, the registry does not report the IKd median PFS or the upper confidence bound for the Kd median. This limits direct interpretation of the group-specific median times and prevents a complete median-based comparison from the registry record alone.

The primary analysis timeframe is tied to the cut-off date of 7 Feb 2020, with median follow-up of 20.73 months. The study is listed as completed with a primary completion date of 2022-01-14, but the primary endpoint result is specifically the earlier primary analysis. The record does not explain how later follow-up relates to the posted primary result.

The official title describes the study as open label, while the masking field lists single, and the record does not clarify the masking arrangement. The registry does not report the original sample-size justification, interim-analysis plan, multiplicity strategy, or full statistical-analysis plan. Stratification factors for the primary test are not described. Population definitions for secondary outcomes and missing-data procedures beyond the stated PFS censoring rules are also not reported.

For safety, the listed serious adverse-event terms are not attributed to a treatment group in the record excerpt, and the counts alone do not establish causation. The registry’s secondary results span multiple outcome types, but not every sponsor analysis is posted. These limitations concern the completeness and interpretability of the registry record; they should not be treated as evidence that an unreported procedure was not carried out.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Multinational Clinical Study Comparing Isatuximab, Carfilzomib And Dexamethasone To Carfilzomib And Dexamethasone In Relapse And/Or Refractory Multiple Myeloma Patients — NCT03275285.
• Registry record last updated 2026-02-09; status last verified 2026-02.
• Results first posted 2023-02-13.
• 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.

23. Record Summary

NCT03275285 is a completed, randomized phase 3 study comparing isatuximab with carfilzomib and dexamethasone against carfilzomib and dexamethasone in participants with relapse and/or refractory multiple myeloma previously treated with 1 to 3 prior lines. The registry records 302 participants enrolled and identifies PFS assessed by an independent response committee as the primary outcome.

The sponsor-reported primary analysis gives a hazard ratio of 0.531 for Kd versus IKd, with a 99% confidence interval from 0.318 to 0.889 and p < 0.001. Response outcomes and adverse-event counts are also posted. The registry record does not report a complete set of arm-specific median PFS results, the original design assumptions, or several details of the statistical plan, which limits interpretation of the result beyond the reported analysis.