Randomized Trial of Lenalidomide, Bortezomib, Dexamethasone vs High-Dose Treatment With SCT in MM Patients up to Age 65: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Randomized Trial of Lenalidomide, Bortezomib, Dexamethasone vs High-Dose Treatment With SCT in MM Patients up to Age 65 (NCT01208662), a randomized phase 3 study. The primary outcome is Median Progression-Free Survival (PFS).

2. Clinical Question

The primary endpoint was time from randomization to disease progression, as determined by central review, or death from any cause, whichever occurred first. The posted results report median progression-free survival and a hazard ratio for the comparison. The trial description states that high-dose treatment would be considered superior if it significantly prolonged progression-free survival by at least 9 months or more, while recognizing that particular subgroups might benefit more. That description expresses the trial’s stated objective; it is not a substitute for the complete statistical analysis plan, which is not reported in the registry record.

The randomized comparison addresses the overall contrast between the assigned treatment approaches. It does not, by itself, establish whether effects differ among subgroups. The registry record identifies multiple myeloma as the condition and describes the population as patients up to age 65, but does not report detailed eligibility criteria in the information summarized for these results.

3. Trial Design

This was a randomized, phase III, parallel-group trial with no masking. The registry lists enrollment of 729 and identifies the primary analysis population as all randomized participants. The posted arm counts for the primary endpoint are 357 for RVD alone and 365 for RVD plus ASCT. Randomization followed an initial RVD cycle; participants then received additional RVD cycles and underwent stem-cell collection before continuing in their assigned group.

In the RVD-alone group, the arm description states that participants received five additional RVD cycles. In the RVD-plus-ASCT group, participants received high-dose treatment with autologous stem cell transplantation. The available arm descriptions are incomplete, and the full treatment and maintenance details are not reported in the registry record. Both groups are described as receiving maintenance, but the description does not provide enough detail to characterize that treatment fully.

The trial began in 2010-09, and its listed primary completion date is 2022-02. Its status is active, not recruiting. These registry entries describe the trial record; they do not establish that every outcome or follow-up activity has concluded.

The primary endpoint was assessed over follow-up, with disease assessments every cycle up to maintenance and every 3 cycles on maintenance. During long-term follow-up, disease was assessed every 2 months until progression or death. The registry reports median and maximum PFS follow-up as 70 and 129 months, respectively. It also lists 17 outcome measures and 8 analyses, while only some outcome results are described in the posted information. The trial’s original sample-size justification, detailed allocation procedures, and any interim analyses 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.

Induction and Consolidation

Reasons for not completing this period:

Maintenance

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis population is comprised of all randomized participants.

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 enrolled participants.

6. Primary Endpoint

The registry lists the primary outcome as Median Progression-Free Survival (PFS), measured over On treatment, disease was assessed every cycle up to maintenance and every 3 cycles on maintenance. In long-term follow-up, disease was assessed every 2 months until PD or death. Median (maximum) PFS follow-up was 70 and 129 months..

Progression-free survival (PFS) measures the time from randomization until the earlier of disease progression or death from any cause. Progression was determined by central review using International Myeloma Working Group uniform response criteria. The endpoint therefore captures either progression or death as an event, rather than requiring both to occur.

Time-to-event outcomes are useful when participants can have different lengths of follow-up and when the timing of an event matters. The Kaplan-Meier method estimates the probability of remaining free of the defined event over time while accounting for participants whose follow-up ends before an event is observed. The median PFS is the estimated time by which half of the population has experienced an event, according to that survival curve. It is not an average follow-up time or a direct measure of how long every participant remained progression-free.

The registry specifies censoring rules. Participants who started non-protocol therapy were censored at its start date when available, or at the date treatment ended if the start date was missing. Participants without non-protocol therapy, progression, or death were censored at their last disease evaluation. Deaths occurring beyond 1 year from the date last known to be progression-free were not counted as events and were censored at the last disease evaluation. These rules affect which observations contribute to the estimated survival curve and should be considered when interpreting the endpoint.

7. Results Posted in the Registry

• RVD Alone vs RVD Plus ASCT: hazard ratio 1.53 (95% CI 1.23–1.91), 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.

Partial Response (PR) Rate

• 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:
  • RVD Plus ASCT: 97.5% (356/365) versus 95.0% (339/357) on control; risk difference 2.6 percentage points (95% CI -0.2 to 5.3), risk ratio 1.03 (1.00–1.06); unadjusted two-proportion z-test p = 0.068.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between RVD Plus ASCT and the control. The interval gives the range of effects that remain compatible with the data.

Very Good Partial Response (VGPR) Rate

• 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:
  • RVD Plus ASCT: 82.7% (302/365) versus 79.6% (284/357) on control; risk difference 3.2 percentage points (95% CI -2.5 to 8.9), risk ratio 1.04 (0.97–1.12); unadjusted two-proportion z-test p = 0.273.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between RVD Plus ASCT and the control. The interval gives the range of effects that remain compatible with the data.

Complete Response (CR) Rate

• 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:
  • RVD Plus ASCT: 46.8% (171/365) versus 42.0% (150/357) on control; risk difference 4.8 percentage points (95% CI -2.4 to 12.1), risk ratio 1.12 (0.95–1.31); unadjusted two-proportion z-test p = 0.191.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between RVD Plus ASCT and the control. The interval gives the range of effects that remain compatible with the data.

The response outcomes point in a generally similar descriptive direction: the posted response proportions are higher in the RVD-plus-ASCT group for partial response, very good partial response, and complete response. These outcomes are not the primary endpoint, and their comparisons do not replace the time-to-event analysis. They describe response categories rather than the duration until progression or death.

The sponsor-reported Fisher exact tests do not provide the same strength of statistical evidence across response categories. The unadjusted recalculations also have uncertainty intervals that include no difference for the listed comparisons. This broad pattern does not establish a reliable difference in response rates, and it does not contradict the primary PFS finding: response status and PFS measure different aspects of the treatment comparison.

Secondary endpoints can provide supporting context, but they carry less weight when many outcomes are examined and no multiplicity adjustment or testing hierarchy is reported. Testing many outcomes raises the chance that some results may appear notable by chance. The registry lists 17 outcome measures and 8 analyses, but the multiplicity strategy is not reported in the registry record. Accordingly, individual secondary p-values should be treated as exploratory unless a prespecified plan establishes otherwise.

The posted secondary outcomes also vary in definition and follow-up. Response measures depend on assessment criteria and timing, while time-to-progression, overall survival, adverse events, and second primary malignancy have different event definitions. The registry lists these outcomes, but the results summarized for interpretation do not include all of them. The overall response pattern can inform the context of the primary result, but it cannot establish effects on unreported endpoints or identify subgroup-specific patterns.

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

• Partial Response (PR) Rate
• Very Good Partial Response (VGPR) Rate
• Complete Response (CR) Rate
• Median Duration of Response: Partial Response (DOR PR)
• 5-Year Time to Progression (TTP)
• 5-Year Overall Survival (OS)
• Grade 3 or Higher Treatment-Related Non-Hematologic Adverse Event (AE) Rate
• 5-year Cumulative Incidence of Second Primary Malignancy (SPM)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint uses time-to-event methods. These methods are designed for outcomes where the event can occur at different times and where some participants have no observed event before their follow-up ends. In this trial, the event was progression or death, according to the endpoint definition. Participants without an observed event by the relevant censoring date contribute information up to that time; they are not treated as though they experienced the event at the end of follow-up.

What does the Kaplan-Meier estimate describe?

The Kaplan-Meier method estimates the probability of remaining free of the event over time. It updates the estimated survival curve as events occur and accounts for participants who are censored. The median is read from this estimated curve as the time at which the estimated proportion remaining event-free reaches one half. It is a summary of the curve, not a claim that each participant experienced the event at that time.

The registry defines the endpoint from randomization to progression by central review or death from any cause. It also describes specific censoring rules for non-protocol therapy, last disease evaluation, and deaths occurring beyond 1 year from the date last known progression-free. Censoring is an analysis convention: it marks the point at which a participant’s event status stops contributing to the estimate. Interpretation depends on how well the rules and follow-up represent the experience of the randomized groups.

How should the hazard ratio be read?

The hazard ratio compares event hazards between groups over time. The reported contrast is RVD alone versus RVD plus ASCT, with a hazard ratio of 1.53 and a 95% confidence interval from 1.23 to 1.91. In the usual interpretation of this ordering, values above 1 indicate a higher event hazard in the first group relative to the second. This is not the same as comparing median PFS values, and it is not an absolute risk difference. The log-rank method is the reported method for the comparison; the registry does not provide enough detail to characterize every modeling assumption or diagnostic assessment.

A confidence interval expresses uncertainty around an estimate under the method used. It reflects the range of values reasonably compatible with the data and analysis, rather than a range containing a specified proportion of individual participant outcomes. A p-value addresses how compatible the observed comparison is with a null hypothesis under the test’s assumptions. It does not quantify the size or importance of an effect. These measures answer different questions and should be read together with the endpoint definition and follow-up.

Why do censoring rules matter?

Participants may start non-protocol therapy, stop being observed, or have a last disease assessment before the end of the study period. The registry states that participants starting non-protocol therapy were censored at its start date when available, or at the date treatment ended when the start date was missing. Participants who had not started non-protocol therapy, progressed, or died were censored at their last disease evaluation. For deaths occurring beyond 1 year from the date last known progression-free, the registry says these were not counted as events and were censored at the last disease evaluation. These choices determine which follow-up time is included in the PFS estimate.

Outcome assessment was scheduled every cycle up to maintenance and every 3 cycles on maintenance, followed by assessments every 2 months during long-term follow-up until progression or death. The registry reports median and maximum PFS follow-up as 70 and 129 months. Follow-up schedules and censoring practices are important because time-to-event estimates rely on the observed event and censoring information, not solely on the total enrollment.

General statistical consideration: if censoring is related to a participant’s underlying chance of experiencing the event, standard time-to-event estimates may not fully represent the group’s event experience. The registry record describes the censoring rules but does not report analyses that test this assumption.

What does the log-rank test contribute?

The log-rank test compares the event-time experience of groups across follow-up. It uses information from the timing of events and the number of participants still at risk, rather than treating the endpoint as a simple yes-or-no outcome at one fixed time. The reported log-rank result is p < 0.001. That result indicates statistical evidence against the test’s null comparison under its assumptions; it does not by itself describe the magnitude, clinical importance, or persistence of a difference.

The registry reports a superiority analysis. The trial description states that high-dose treatment would be considered superior if it significantly prolonged PFS by at least 9 months or more. The posted statistical result is a hazard ratio and its confidence interval, together with the log-rank p-value. The registry record does not report enough information to determine how the stated months-based criterion was incorporated into the final analysis or whether other prespecified decision rules applied.

What is different about response outcomes?

Response rates are binary outcomes: each participant is classified according to whether a response category was reached under the assessment rules. The registry lists partial response, very good partial response, and complete response among the secondary outcomes. The sponsor’s reported analyses for these rates use Fisher exact tests. The separate unadjusted recalculations use posted summary counts and are not the same as a complete participant-level analysis. In general, binary response comparisons do not use event timing in the way PFS methods do.

General statistical consideration: binary-outcome comparisons can be sensitive to the response definition, the assessment window, and how missing assessments are handled. The registry describes assessment frequency and treatment duration for some outcomes, but the missing-data procedures for response analyses are not reported in the registry record. Detailed assumptions for the original sample-size design and the full analysis plan are also not reported in the registry record.

11. Confidence Intervals and Precision

The PFS median for RVD alone is 46.2 months, with a 95% confidence interval from 38.1 to 53.7 months. The median for RVD plus ASCT is 67.5 months, with a lower confidence limit of 58.6 months; an upper limit is not reported in the registry record. The asymmetry in what is reported means the precision of the second median cannot be described by a complete two-sided interval from the registry information.

The hazard ratio of 1.53 has a 95% confidence interval from 1.23 to 1.91. This interval indicates uncertainty around the relative hazard estimate: values across that range are compatible with the data under the reported analysis and its assumptions. The interval is above 1, consistent with the direction of the reported comparison. It does not mean that the hazard ratio is equally likely to be any value in the interval, nor does it describe the range of individual outcomes.

Confidence intervals for medians and for a hazard ratio answer different questions. The median intervals describe uncertainty in each group’s estimated median, while the hazard-ratio interval describes uncertainty in the relative comparison. Comparing overlap between separate median intervals is not a replacement for the reported test of the between-group contrast. The log-rank p-value and hazard-ratio interval address the comparison more directly.

Precision also depends on the number and timing of observed events, follow-up, and censoring. The registry provides group sizes, follow-up information, and censoring rules, but does not give a full account of event counts for the primary analysis or a detailed missing-data assessment. The posted estimates should therefore be interpreted with the stated confidence intervals and endpoint rules, rather than as exact values without uncertainty.

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 sample-size displays are planning illustrations based on the observed effect, not the trial’s original design assumptions. For PFS, the entries are total event counts needed under the listed scenarios; they are not participant counts per arm. For the binary outcomes, the entries are participants per arm. The assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each scenario uses the stated fraction of the observed effect.

The 80% power column gives the planned number of total events, or participants per arm for a binary outcome, for a design that would have an 80% chance of detecting the assumed effect under those planning assumptions. The 90% power column gives the corresponding requirement for a design with a 90% chance. These are planning properties for hypothetical future designs, not measurements of what happened to the participants in this trial. This is not observed power.

The rows that plan for 100%, 75%, and 50% of the observed effect show how the required event or participant count changes when the effect to be detected is smaller. A smaller effect is harder to distinguish from random variation under otherwise similar assumptions, so it requires more information and therefore more events or participants. The displays are illustrations, not a reconstruction of the trial’s sample-size justification. The original design assumptions and justification are not reported in the registry record.

For a time-to-event outcome, event accrual is central: participants with longer follow-up but no event do not contribute the same event information as participants who experience the endpoint. The PFS planning figures therefore use total events. For the response outcomes, the planning figures count participants in each arm. These planning counts should be read in their respective units rather than compared as though they represented the same quantity.

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 = 1.530, so ln(HR) = 0.4253.
2. d = 4 × (1.96 + 0.842)² / [ln(1.530)]² = 173.6, rounded up to 174 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 <- 1.53                              # 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(1208662)
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 = 174 (80% power), 233 (90% power)
 75% of observed effect: events = 309 (80% power), 414 (90% power)
 50% of observed effect: events = 695 (80% power), 930 (90% power)
Simulated power with 174 events: 0.812 (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

For the primary endpoint, the sponsor-reported analysis is a log-rank comparison with a hazard ratio of 1.53, a 95% confidence interval from 1.23 to 1.91, and p < 0.001. The displayed primary result is the sponsor’s reported analysis; no separate recalculated primary comparison is presented in the registry information.

For the secondary response outcomes, the registry reports Fisher exact tests. The separate unadjusted recalculations use the posted group counts and compare proportions without adjustment. Those calculations are useful as simple checks based on summary statistics, but they are not substitutes for the sponsor’s own reported analysis or a participant-level analysis. The registry’s response results include sponsor-reported p-values, while the recalculated contrasts have their own estimates and uncertainty. These should not be treated as interchangeable when their methods and inputs differ.

No discrepancy is flagged for the posted results. The registry record does not provide enough information to reconcile every difference between the sponsor-reported binary tests and the unadjusted recalculations, including whether the analyses used exactly the same populations, outcome handling, or procedures. For interpretation of the trial’s reported conclusions, the sponsor’s own analysis is the primary reference; recalculations provide context only.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists numerous outcome measures and analyses, including the primary PFS endpoint and multiple secondary outcomes. A prespecified hierarchy, family-wise error control, false-discovery procedure, or other multiplicity adjustment is not reported in the registry record. Without that information, the sponsor-reported p-values for secondary outcomes should not be interpreted as though they necessarily account for testing multiple outcomes. The original analysis plan and any interim-analysis plan are also not reported in the registry record.

The primary analysis population is described as all randomized participants. For PFS, the registry provides detailed event and censoring definitions, including the handling of non-protocol therapy, last disease evaluation, and certain deaths. These rules are part of the endpoint analysis, but they do not answer every missing-data question. The registry does not report a general missing-data strategy for the response outcomes, the extent of missing observations for each endpoint, or sensitivity analyses addressing missingness.

The outcome assessment schedule is described for PFS and for response rates. Scheduled assessment does not establish that every participant had every assessment or that missing assessments were handled in the same way across endpoints. The registry record does not report the detailed disposition of participants by endpoint, analysis-specific exclusions, or the handling of missing response classifications.

These omissions limit how fully the posted results can be independently reconstructed. They do not invalidate the reported analysis, but they mean that interpretation must remain anchored to the methods and population stated in the registry. The trial’s original sample-size assumptions, full statistical analysis plan, subgroup procedures, and any interim monitoring approach are not reported in the registry record.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: neutropenia (86.3%), thrombocytopenia (82.7%), leukopenia (39.7%), anemia (29.6%), acute coronary syndrome (14.3%).

The serious adverse event summary lists 279 affected participants among 357 at risk in the RVD-alone group, and 344 affected participants among 365 at risk in the RVD-plus-ASCT group. These are participant counts in the registry summary; they do not describe the number of serious-event episodes, their duration, or their severity beyond the serious-event classification. The record also lists a separate RVD Cycle 1 Only group with 4 affected among 7 at risk. That small separate group should not be combined with either randomized treatment arm.

The most frequently listed serious terms include neutropenia, thrombocytopenia, leukopenia, anemia, acute coronary syndrome, and elevated liver enzymes, with percentages reported for each term. The registry summary does not provide enough detail in this information to establish whether the percentages use participants, events, or another denominator, so they should be read as posted rather than reinterpreted. Death counts are also listed by group, but the summary does not specify that these deaths were treatment-related.

These safety figures are descriptive. The registry information does not provide a formal between-group safety analysis or adjusted comparison. Counts should be considered alongside exposure and follow-up, which can differ between groups.

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

The posted primary analysis indicates a statistically significant difference in PFS between the randomized groups under the registry’s endpoint definition and log-rank analysis. Median PFS was 46.2 months for RVD alone and 67.5 months for RVD plus ASCT. The reported hazard ratio for RVD alone versus RVD plus ASCT was 1.53, with a 95% confidence interval from 1.23 to 1.91 and p < 0.001. These estimates describe the overall randomized comparison over the recorded follow-up.

The result does not mean that every person assigned to RVD plus ASCT had a better outcome than every person assigned to RVD alone. A group-level hazard ratio does not predict an individual participant’s outcome. Nor does the median difference indicate that all participants experienced an additional duration equal to the distance between the medians. Individual outcomes vary, and the survival curves contain information not captured by a single median.

The result also does not answer every question about the treatment strategies. It does not establish effects for particular subgroups, effects on every secondary endpoint, or the balance of benefits and harms for an individual. The available safety summary is descriptive, and the registry record does not report a formal comparative safety analysis in the information. The secondary response outcomes are not substitutes for PFS, and multiplicity procedures are not reported.

Interpretation is tied to the specified progression and death event definition, central review, follow-up schedule, and censoring rules. The registry also states that deaths beyond 1 year from the date last known progression-free were censored rather than counted as events. Those details affect the estimand represented by the posted PFS analysis. The data therefore support a reading of the reported overall comparison, not a broader claim beyond the population, endpoint, and analysis recorded.

18. Why This Trial Matters Statistically

This trial is statistically notable because its primary outcome is time to an event, not a response proportion measured at a single point. Time-to-event analysis uses both whether an event occurred and when it occurred, while accommodating participants whose event status is not observed through the full follow-up period. That makes the endpoint definition and censoring rules central to understanding the estimate.

The comparison also illustrates why a median and a hazard ratio should be read together. The medians describe the midpoint of each estimated PFS curve, while the hazard ratio summarizes the relative event hazard across follow-up under the reported analysis. They are complementary summaries, not interchangeable forms of the same quantity. Confidence intervals add information about uncertainty that a point estimate alone cannot convey.

The study’s design addresses a treatment-strategy question in which both groups received RVD and the randomized contrast concerned high-dose treatment with ASCT. This makes the treatment contrast more specific than a comparison of wholly unrelated regimens. The primary analysis reports a clear statistical signal, while secondary outcomes and descriptive safety information require separate interpretation.

The record also highlights practical limits of registry-based reading. Important items—including original sample-size justification, multiplicity procedures, missing-data handling for secondary outcomes, and interim-analysis details—are not reported in the registry record. Recognizing those limits helps distinguish what the analysis directly estimates from what would require a full protocol or analysis plan.

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.

The available registry information leaves several trial-specific details unresolved. The arm descriptions are truncated, so the full treatment schedule, maintenance regimen, and other protocol details are not reported in the registry record. The original sample-size justification and assumptions, interim analyses, and complete statistical analysis plan are also not reported.

The primary outcome has an upper confidence limit reported for RVD alone but not for RVD plus ASCT. The registry states that the median and maximum PFS follow-up were 70 and 129 months, but the information does not provide a complete event-count breakdown or risk-set details across time. Those omissions restrict independent assessment of the amount of information contributing to later follow-up.

The PFS analysis has specific censoring rules, including censoring after initiation of non-protocol therapy and for certain deaths occurring beyond 1 year from the last known progression-free date. These rules are part of the stated analysis and should be considered when interpreting the estimate. The registry does not report sensitivity analyses showing how results might change under alternative censoring assumptions.

For secondary outcomes, the registry does not report a multiplicity strategy, comprehensive endpoint-specific missing-data procedures, or detailed analysis populations. The listed safety counts are descriptive, and the summarized record does not provide a formal comparative safety analysis. These limitations do not negate the reported PFS analysis, but they narrow the conclusions that can be drawn from the registry record alone.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Randomized Trial of Lenalidomide, Bortezomib, Dexamethasone vs High-Dose Treatment With SCT in MM Patients up to Age 65 — NCT01208662.
• Registry record last updated 2026-01-22; status last verified 2026-01.
• Results first posted 2023-12-18.
• 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

NCT01208662 is a randomized, phase III, parallel-group trial comparing RVD alone with RVD plus autologous stem cell transplantation in patients with newly diagnosed multiple myeloma up to age 65. The trial was unmasked, and the registry lists enrollment of 729. Its status is active, not recruiting.

The primary endpoint was median PFS, defined as time from randomization to progression by central review or death from any cause. The reported median was 46.2 months for RVD alone and 67.5 months for RVD plus ASCT. The hazard ratio for RVD alone versus RVD plus ASCT was 1.53, with a 95% confidence interval from 1.23 to 1.91 and p < 0.001.

Secondary response outcomes and descriptive adverse-event summaries provide additional context. The registry record does not report the full original statistical plan, multiplicity strategy, or all missing-data procedures, so interpretation should remain focused on the stated endpoint and posted analyses.