S1211 Bortezomib, Dexamethasone, and Lenalidomide With or Without Elotuzumab in Treating Patients With Newly Diagnosed High-Risk Multiple Myeloma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for S1211 Bortezomib, Dexamethasone, and Lenalidomide With or Without Elotuzumab in Treating Patients With Newly Diagnosed High-Risk Multiple Myeloma (NCT01668719), a randomized phase 1, phase 2 study. The primary outcome is Progression-free Survival.

2. Clinical Question

3. Trial Design

NCT01668719, titled S1211 Bortezomib, Dexamethasone, and Lenalidomide With or Without Elotuzumab in Treating Patients With Newly Diagnosed High-Risk Multiple Myeloma, was a phase I/II study sponsored by SWOG Cancer Research Network. The registry labels it partially randomized, randomized in allocation, parallel in model, and unmasked. Enrollment is listed as 142, and the study status is completed. The registry gives a start date of 2012-11 and primary completion date of 2020-02-05.

The treatment comparison was between bortezomib, lenalidomide, and dexamethasone alone and the same combination with elotuzumab. The arm descriptions specify induction treatment repeating every 21 days for 8 courses, subject to disease progression or unacceptable toxicity. In the elotuzumab arm, elotuzumab was added on the schedule described in the registry. The descriptions also allow specified routes of administration for some drugs. These are protocol descriptions, not evidence that all participants completed treatment as planned.

The primary outcome was progression-free survival, defined from registration to first documented progression or death from any cause. Its timeframe is listed as up to 6 years post registration. The primary endpoint record includes 52 participants for Arm I and 48 for Arm II. The registry’s overall enrollment and the endpoint-specific arm counts describe different aspects of the record; the reasons for the endpoint counts and any exclusions are not reported in the registry record.

The study also lists overall survival, response of partial response or better, and grade 3 through 5 adverse events related to study drugs among secondary outcomes. Numerical results are posted for response, while analyses for the other listed secondary outcomes are not reported in the registry record. The phase I component and the partly randomized design warrant care in interpreting the arm-level safety descriptions as if they were a simple randomized comparison.

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: 8 participants were enrolled to the Phase 1 Level 1 dose arm. 2 were ineligible, so 6 participants were assessed for DLT. In Phase II, 68 participants were enrolled on RVD and 66 to RVD/Elo arm. of these, 16 and 18 respectively were ineligible. Thus, 52 participants on RVD and 48 participants on RVD/Elo arm were eligible and evaluable for analyses.

Phase I

Reasons for not completing this period:

Phase II

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: At the time of the phase I analysis, six participants were evaluable for DLTs (i.e. were eligible and received at least one dose of study drug).

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: All eligible participants

6. Primary Endpoint

The registry lists the primary outcome as Progression-free Survival, measured over Up to 6 years post registration.

Progression-free survival measures the time from registration until the first documented disease progression or death from any cause. In this study, progression was defined according to the International Uniform Response Criteria for Multiple Myeloma. The listed criteria include changes in serum or urine M protein, changes in involved and uninvolved serum free light chains under specified baseline conditions, increased bone marrow plasma cells, new or enlarging bone lesions or soft tissue plasmacytomas, and hypercalcemia attributed solely to multiple myeloma.

This time-to-event endpoint is used because it combines the timing of disease progression and death into a clinically relevant measure of how long participants remain alive without either event. As a general statistical point, time-to-event methods can use information about when an event occurred rather than reducing follow-up to a simple event count. Interpretation still depends on how follow-up, censoring, and endpoint assessment were handled; those details are not reported in the registry record.

The registry reports median progression-free survival of 33.6 months for Arm I, with a 95% confidence interval from 19.6 months and no upper limit reported, and 31.5 months for Arm II, with a 95% confidence interval from 18.6 to 54.0 months. A median describes the point by which half of the analyzed group is estimated to have experienced the event. These are arm-specific estimates. Without a reported between-arm hazard ratio or other sponsor analysis, they should not be read as a formal estimate of the relative treatment effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Progression-free survival is a time-to-event outcome: each participant’s outcome depends on the time until progression or death, rather than only whether an event occurred. The registry gives a median and a 95% confidence interval for each arm. The median is an estimate of the time by which half the analyzed group has experienced the defined event. A confidence interval conveys uncertainty in that estimate; a wider interval indicates less precision. The reported intervals are compatible with a range of median values, and Arm I has no upper confidence limit reported.

Why is the primary comparison not available?

Comparing treatment arms for a time-to-event outcome commonly requires a contrast that uses event-time information, such as a hazard ratio, along with its uncertainty. The record reports arm-specific medians but does not report a sponsor-derived hazard ratio or a p-value for the primary comparison. A difference between the posted medians is not a substitute for that analysis. It would be a new calculation and would not capture all of the information in the event-time distributions. The record indicates that a two-arm comparison is not estimable from the posted median endpoint values.

As a general explanation, a hazard ratio summarizes the relative rate of experiencing the event over follow-up under the assumptions of the model used. It is not the same as a ratio of medians and does not directly describe an individual participant’s probability of progression or death. The registry record does not report a hazard ratio, its confidence interval, the model used for a primary comparison, or the assumptions checked for that model.

How should the response comparison be read?

Response of partial response or better is a binary outcome: a participant either meets the response threshold or does not. The posted arm estimates are 88.0% for Arm I and 83.0% for Arm II. The corresponding recalculated unadjusted risk difference is -0.055, with a 95% confidence interval from -0.193 to 0.083. The interval includes zero, which represents no difference in response proportions on the risk-difference scale. The unadjusted p-value is 0.434. These are unadjusted estimates, not a reported sponsor analysis. No adjusted response analysis is reported in the registry record.

A confidence interval communicates both the direction and the precision of an estimate. For this response contrast, the interval includes possible effects favoring either arm, so the data do not provide a precise estimate of the direction of the difference. A p-value is a measure of how compatible the observed data are with a specified null model; it is not the probability that the null hypothesis is true, nor does it indicate the size or clinical importance of an effect. It should be considered alongside the estimate and its interval.

What do the planning illustrations mean?

The response planning illustrations use the observed effect as a basis for hypothetical sample-size calculations. They list participants per arm for 80% power and participants per arm for 90% power, under a two-sided significance level of 0.05, equal allocation, and a normal approximation. Separate rows consider planning for 100%, 75%, and 50% of the observed effect. For planning for 100% of the observed effect, the illustrations give 639 participants per arm for 80% power and 854 for 90% power. For planning for 75% of the observed effect, they give 1,090 participants per arm for 80% power and 1,458 for 90% power. For planning for 50% of the observed effect, they give 2,348 participants per arm for 80% power and 3,142 for 90% power.

These figures are hypothetical planning illustrations, not observed power and not the trial’s original sample-size target or justification. The record explicitly describes them as computed from the observed effect rather than from the trial’s own design. The sample-size justification for the original trial is not reported in the registry record. As a general statistical point, planning estimates depend on the assumed effect, allocation, significance level, and method; changing those assumptions can change the resulting sample-size requirement.

Why does over-dispersion matter in general?

Over-dispersion occurs when variation in data is greater than a statistical model assumes. If ignored, standard errors can be too small and confidence intervals too narrow, making estimates appear more precise than warranted. This general issue can matter for some count or clustered outcomes. The registry record does not report whether over-dispersion was assessed or relevant to the analyses in this trial, so it cannot be claimed to have affected the posted results.

The record identifies no sponsor-reported statistical analyses for the posted secondary outcomes. It also does not report the primary analysis model, handling of censoring, interim analyses, or multiplicity procedures. These absences constrain independent statistical appraisal. They do not establish that such procedures were or were not conducted; the details are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a multiplicity procedure. This matters because the study lists several secondary outcomes in addition to its primary progression-free survival outcome. As a general statistical principle, testing multiple outcomes can increase the chance of a nominally unusual result arising by chance. Without a stated testing hierarchy or adjustment, the unadjusted secondary response comparison should be interpreted cautiously rather than as confirmatory evidence.

The record does not report whether interim analyses were conducted, whether the primary analysis was adjusted for prognostic factors, or what statistical model was used for the primary time-to-event outcome. It does not report a sample-size justification for the trial’s original design. The response planning illustrations are explicitly based on the observed effect and are not the original design calculation.

The primary endpoint population is described as eligible and analyzable participants. The registry does not report an intention-to-treat population, the rules used to determine analyzability, or how participants with missing assessments were handled. It also does not report follow-up completeness, censoring rules, or sensitivity analyses for missing data. Those details are important for evaluating whether incomplete outcome information could have changed the estimates.

The endpoint-specific arm counts differ by outcome: progression-free survival lists 52 for Arm I and 48 for Arm II, while the response result lists 52 for Arm I and 47 for Arm II. The record does not explain the difference in the Arm II counts. It is therefore not possible to infer from the posted record why a participant is absent from an endpoint analysis or whether the difference reflects missing data, eligibility rules, or another reason. These are limitations of the registry information, not proof that the underlying study lacked an analysis plan.

11. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: treatment related secondary malignancy (33.3%), infections and infestations-other (16.7%), skin infection (16.7%), nervous system disorders-other (16.7%), thromboembolic event (16.7%).

The safety record lists adverse-event counts separately for a phase I elotuzumab dose-level group and the two named treatment arms. In the Phase I Dose Level 1 group, 3 participants are listed with serious adverse events among 6 at risk. Arm I lists 6 with serious adverse events among 52 at risk, and Arm II lists 24 among 48 at risk. The record also lists other adverse events for these groups: 6 among 6, 52 among 52, and 47 among 48, respectively. These are registry counts and should not be treated as a randomized safety comparison without accounting for the phase I group and the trial design.

The listed serious adverse-event terms include treatment related secondary malignancy at 33.3%, infections and infestations-Other at 16.7%, skin infection at 16.7%, nervous system disorders-Other at 16.7%, thromboembolic event at 16.7%, and lung infection at 14.6%. The record also gives death counts by group, but the basis and attribution of those counts are not described in the safety summary. Counts and percentages alone do not establish causality, comparative risk, or the full clinical context of events. Definitions, event ascertainment details, and a formal comparative safety analysis are not reported in the registry record.

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

The posted primary results describe median progression-free survival in each treatment arm. They do not include a formal sponsor-reported comparison of the arms. The medians and confidence intervals therefore show the estimated event-time experience and its uncertainty within each arm, but do not establish whether adding elotuzumab changed progression-free survival. The missing between-arm analysis is an important limit on what can be concluded statistically.

The response outcome has a recalculated unadjusted contrast and confidence interval. That estimate is uncertain, and the interval includes no difference as well as effects in either direction. It is a secondary result and does not settle the primary time-to-event question. Results for overall survival and the listed drug-related adverse-event outcome are not reported in the registry record, limiting assessment of whether the secondary outcomes align with the primary result.

These findings do not establish that either regimen works or does not work. Nor do they establish equivalence or no effect: the absence of a definitive reported comparison is not evidence that the treatment strategies are the same. Clinical decisions require broader evidence and individual context; the registry results alone are not medical advice.

The trial was partially randomized and unmasked, and includes a phase I component. The registry record does not provide enough analysis detail to assess all potential sources of bias, including missing data, endpoint assessment, and analysis-population choices. The posted values should therefore be read as a limited account of the trial’s registered results rather than a complete independent evaluation of efficacy and safety.

13. Why This Trial Matters Statistically

This trial illustrates why an arm-specific median is not the same as a treatment comparison. Readers may be tempted to compare the two progression-free survival medians directly, but that would not provide the full event-time contrast or its uncertainty. A time-to-event treatment effect is better represented by an analysis that uses the follow-up and event-time information, with an estimate and uncertainty measure. The registry record does not report that primary comparison.

It also illustrates the importance of endpoint-specific populations. The registry lists different arm counts for progression-free survival and response, but does not explain the difference. Understanding who contributed data to each endpoint is necessary for assessing whether the results answer the intended question and how missingness may affect interpretation.

Finally, secondary outcomes and sample-size calculations require context. An unadjusted response comparison is not a substitute for the primary result, especially when a multiplicity plan is not reported. Likewise, planning illustrations based on an observed effect are not observed power and do not explain the trial’s original sample-size design. Distinguishing these statistical roles helps prevent descriptive estimates, exploratory comparisons, and hypothetical planning figures from being treated as interchangeable evidence.

14. 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 registry record has several trial-specific limitations for interpretation. Although it identifies the study as partially randomized, it does not describe which participants or phases were randomized, or how the phase I dose-level group relates to the phase II arms. The record indicates no masking, but does not describe safeguards for outcome assessment. These details matter when considering the potential for differences in allocation or assessment to influence results.

The primary endpoint is reported as arm-specific medians, without a sponsor-reported hazard ratio or formal comparison. One confidence interval has no upper limit reported. The registry does not provide event counts, follow-up distributions, censoring details, or a primary statistical model, so the precision and assumptions underlying the estimates cannot be fully assessed.

The endpoint-specific arm counts differ between progression-free survival and response, and the reason is not reported. The analysis population is described only as eligible and analyzable participants. Missing-data handling, exclusions, and sensitivity analyses are not reported. The registry also lists secondary outcomes for which comparative numerical results are unavailable in the record.

The safety summary includes a phase I dose-level group alongside the treatment arms, but does not report a formal comparative analysis or enough detail to interpret event attribution. Taken together, these limitations mean that the registry provides useful descriptive results but an incomplete basis for judging comparative efficacy and safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: S1211 Bortezomib, Dexamethasone, and Lenalidomide With or Without Elotuzumab in Treating Patients With Newly Diagnosed High-Risk Multiple Myeloma — NCT01668719.
• Registry record last updated 2026-04-28; status last verified 2026-04.
• Results first posted 2021-10-27.
• 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.

18. Record Summary

NCT01668719 is a completed, partially randomized phase I/II study of bortezomib, lenalidomide, and dexamethasone with or without elotuzumab in newly diagnosed high-risk multiple myeloma. The registry lists randomized allocation, parallel arms, no masking, and enrollment of 142.

The primary endpoint was progression-free survival from registration to documented progression or death from any cause. Arm-specific medians are posted, but a sponsor-reported between-arm analysis is not reported in the registry record. The secondary response outcome has posted arm estimates and an unadjusted recalculated comparison; comparative results for the other listed secondary outcomes are not reported in the registry record.

Interpretation is limited by missing details about analysis populations, missing data, multiplicity, and the primary time-to-event model. Planning illustrations based on the observed response effect are hypothetical and are not observed power or the original trial design justification.