Phase 2 Multi-center Study of Anti-PD-1 During Lymphopenic State After HDT/ASCT for Multiple Myeloma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 2 Multi-center Study of Anti-PD-1 During Lymphopenic State After HDT/ASCT for Multiple Myeloma (NCT02331368), a na phase 2 study. The primary outcome is The Number of Patients That Achieve Complete Response.

2. Clinical Question

3. Trial Design

This was a phase 2, multicenter, single-group study of anti-PD-1 treatment after high-dose chemotherapy and autologous stem cell transplant for multiple myeloma. It is marked completed in the registry record. The recorded study start was 2015-06, and primary completion was 2017-06. The sponsor is the University of Michigan Rogel Cancer Center.

The intervention group received standard treatment described as high-dose melphalan and autologous stem cell transplantation, followed by lenalidomide maintenance, with MK-3475 added after transplant. The arm description specifies that MK-3475 started on day +14, was administered every 3 weeks, and was planned for 9 doses. The brief summary describes 200 mg intravenously every 3 weeks, whereas the arm description says 200 mg/day every 3 weeks. The registry record does not clarify this difference in wording.

The primary endpoint was complete response at 180 days post-transplant, estimated from observed responders. There were also secondary outcomes concerning the estimated percentage alive without relapse or progression at 2 years and the estimated percentage alive at 2 years. Their numerical results are not reported in the registry record. No control group was included, so the design can describe outcomes in the treated group but cannot isolate the effect of MK-3475 from other treatment or clinical factors through a 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 32 patients were enrolled. 3 withdrew consent prior to treatment. Of the 29 treated, 26 were evaluable for response (subjects who received 2-9 doses of MK-3475 were evaluable). Of the 26, 23 completed end-of-treatment response evaluation.

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: 32 patients were enrolled, however 3 withdrew consent prior to beginning treatment so they were not included in the baseline population analysis.

6. Primary Endpoint

The registry lists the primary outcome as The Number of Patients That Achieve Complete Response, measured over 180 days post-transplant.

The primary endpoint counts participants who achieved complete response at 180 days post-transplant. The registry defines complete response as negative immunofixation of serum and urine, disappearance of any soft tissue plasmacytomas, fewer than 5% plasma cells in bone marrow, and negative bone marrow flow cytometry. The endpoint is therefore a defined disease-response category, not simply a count of participants who received treatment or completed follow-up.

Response endpoints are used in clinical research to describe whether participants meet prespecified criteria for a change in disease status at a particular assessment time. The 180-day timeframe sets the occasion for evaluating this endpoint. The registry says that the response rate was estimated as the observed proportion of complete responders at day 180, but the number of responders and the resulting proportion are not reported in the registry record.

Interpreting this endpoint also depends on who was considered evaluable and who completed the assessment. The record states that 26 treated participants were evaluable for response and 23 completed end-of-treatment response evaluation, but it does not explain how incomplete response evaluations were handled in the final endpoint analysis. The endpoint definition is documented; the reported efficacy result is not.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

In general, a single-group study describes outcomes observed among participants who receive the study regimen. For a binary endpoint such as complete response, the basic summary is the proportion meeting the endpoint in a specified analysis group and at a specified assessment time. Such a proportion answers a descriptive question about the observed cohort. It does not provide a randomized estimate of the difference between treatment and control.

In this study, the planned primary measure was the observed proportion of complete responders at 180 days post-transplant. The registry record does not report the number of responders, the proportion, or a confidence interval. Without those results, the magnitude and precision of the response estimate cannot be assessed. Enrollment, treatment, and evaluability counts describe participant flow, not the endpoint outcome.

Why does the analysis population matter?

General statistical interpretation depends on a clear definition of who enters the denominator. This record distinguishes 32 enrolled participants, 29 treated participants, 26 evaluable participants, and 23 who completed end-of-treatment response evaluation. It says participants who received 2–9 doses of MK-3475 were evaluable for response. These groups answer different questions: enrollment concerns consent and entry, treatment concerns exposure, and evaluability concerns whether a participant met a stated condition for inclusion in the response assessment.

The record does not state whether the primary response estimate used the 26 evaluable participants, the 29 treated participants, or another analysis population. It also does not explain how missing assessments or withdrawals were treated in that calculation. These details affect both the numerator and denominator and are important for interpreting a binary response proportion. They are not reported in the registry record.

How should uncertainty be understood?

General explanation: a confidence interval is a range of values compatible with the observed data under a specified statistical procedure. It conveys uncertainty in an estimate; it does not guarantee that the true value lies in the interval or account automatically for every source of bias. For a proportion, uncertainty depends on the observed response count and the analysis denominator, as well as the interval method. Since the response count, response estimate, and interval are not reported in the registry record, its precision cannot be evaluated.

The absence of a control group is a separate limitation from statistical uncertainty. A confidence interval around a single-group response proportion, if available, would describe uncertainty about that cohort’s response frequency under the chosen model. It would not turn the estimate into a comparison with standard care or prove that the added treatment produced the responses.

What do the planned secondary outcomes add?

The record names two secondary outcomes: the estimated percentage of patients alive without relapse or progression at 2 years and the estimated percentage alive at 2 years. These are time-specific outcomes and differ from complete response at 180 days. In general, survival-type outcomes summarize whether participants remain in a defined state by a specified time. Their interpretation depends on outcome definitions, follow-up, censoring, and the method used to estimate the percentage. Those analysis details and the numerical results are not reported in the registry record.

What can a planning illustration show?

General explanation: sample-size planning calculations explore how many participants might be needed under assumptions about an effect size, significance level, allocation, and statistical method. They are planning illustrations, not observed outcomes and not evidence that a study had a particular probability of detecting an effect. The record describes an illustration based on a fraction of the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It notes that time-to-event calculations refer to total events, while other calculations refer to participants per arm. This trial itself was single group, and the registry record does not report the calculated planning values or the trial’s own sample-size justification. The described two-arm planning assumptions should not be mistaken for the design actually used.

Finally, statistical significance and clinical importance are distinct general concepts. A p-value, if available, summarizes compatibility of data with a specified null model under assumptions; it does not measure the size or importance of an effect. No primary p-value or treatment comparison is reported in the registry record. With no reported primary response estimate and no randomized comparator, an efficacy claim cannot be assessed from the posted results.

10. Exact Estimates for Each Arm

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

R code and output

arm    <- c("Anti-PD-1 (MK-3475)")
n      <- c(23)
events <- c(7)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Anti-PD-1 (MK-3475)  23  7  30.4  13.2  52.9  15.6  50.9  15.6  51.1

11. Multiplicity, Missing Data and Analysis Populations

The study lists one primary efficacy endpoint, complete response at 180 days post-transplant, and two secondary outcomes concerning survival without relapse or progression and survival at 2 years. The registry record does not report whether statistical testing was planned for these outcomes, whether the analyses were ordered hierarchically, or whether any adjustment for multiple comparisons was specified. It also does not report an interim analysis plan. These details are not reported in the registry record, so the risk of interpreting multiple outcome tests without a defined multiplicity approach cannot be evaluated.

Missing response data are relevant because the record reports different counts for enrollment, treatment, response evaluability, and completion of end-of-treatment response evaluation. The registry says 26 treated participants were evaluable under its dose-based criterion, while 23 completed the end-of-treatment response assessment. It does not state how participants without a completed assessment were handled for the primary response estimate, or whether the day-180 assessment and end-of-treatment assessment were treated as the same analysis occasion.

The record does not report a statistical analysis plan, the primary analysis population, a missing-data method, or a sensitivity analysis. In general, sensitivity analyses examine whether conclusions change under alternative reasonable assumptions about incomplete observations. Without those details or the response result itself, the effect of missing assessments on the primary estimate cannot be judged. No sample-size justification for the trial is reported in the registry record.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: blood and lymphatic disorder, other (12.5%), thromboembolic event (9.4%), cholecystitis (6.2%), infusion related reaction (3.1%), infections and infestations - other (3.1%).

The registry lists 32 participants at risk for both serious and other adverse events. It reports 14 participants affected by serious adverse events, 30 affected by other adverse events, and 0 deaths. These are participant counts in the safety summary, not measures of event severity beyond the serious-versus-other classification, and the record does not provide participant-level detail in these figures.

The serious-event terms listed include Blood and Lymphatic Disorder, Other (12.5%), Thromboembolic event (9.4%), Cholecystitis (6.2%), Infusion related reaction (3.1%), Infections and infestations - Other (3.1%), and Sepsis (3.1%). The percentages are registry-listed values. The record does not clarify in this summary whether participants could contribute to more than one term or provide enough detail to interpret duration, recurrence, timing, or relatedness to treatment.

These safety summaries describe events reported in the study group. Because there was no control arm, they do not provide a randomized comparison of event rates or establish that MK-3475 caused any listed event. The listed counts and terms should be read as descriptive registry results, not as a complete account of individual risk or a causal attribution.

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

The record establishes that this was a completed phase 2, single-group study of anti-PD-1 treatment after high-dose chemotherapy and autologous stem cell transplantation for multiple myeloma. It specifies a complete-response endpoint at 180 days and reports participant counts at enrollment, treatment, evaluability, and end-of-treatment response assessment. It also reports selected adverse-event summaries and names secondary outcomes at 2 years.

Those details do not reveal the primary efficacy result. The number of complete responders, the estimated response proportion, and its precision are not reported in the registry record. A reader therefore cannot tell from this record how frequently the endpoint occurred or how uncertain an estimate would be. The absence of those data is not evidence that no participants responded; it means the result is unavailable in the registry record.

Even if the single-group response result were available, it would describe the observed treated cohort rather than establish the effect attributable to MK-3475. A randomized control group was not part of the design. The combined treatment context included high-dose melphalan, transplant, lenalidomide maintenance, and MK-3475, so the separate contribution of each component cannot be identified by this design alone.

The safety counts show reported events among participants at risk, including serious and other adverse events and no deaths in the registry summary. They do not establish whether an event was caused by treatment, and the listed terms do not provide a complete account of each participant’s clinical course. The appropriate statistical reading is therefore descriptive: the registry documents a study design and selected observed counts, while key efficacy estimates, analysis details, and causal comparisons are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial illustrates why study design and outcome reporting must be considered together. A phase 2 study can describe how an intervention was administered and whether specified outcomes were observed in a cohort. But a single-group design does not provide the randomized contrast needed to distinguish treatment effects from the other influences on outcomes. The design classification is therefore central to what can be inferred, not just a technical label.

It also demonstrates why participant flow is not a substitute for a response result. Enrollment, treatment, evaluability, and completed assessment counts identify how many people reached different stages, but none gives the number meeting the endpoint. The registry record contains a detailed definition of complete response and a planned assessment time, yet the count and estimated proportion are not reported. Without both the endpoint result and a clear analysis denominator, efficacy and precision remain unassessable.

The contrast between the 180-day primary endpoint and the 2-year secondary outcomes highlights that outcomes can represent different time horizons and clinical questions. Their definitions and analysis methods matter, particularly when follow-up may be incomplete. Those details and results are not reported in the registry record.

Finally, the safety summaries show how registry counts can support a basic description while leaving unanswered questions about event timing, recurrence, and treatment relatedness. Clear statistical interpretation requires distinguishing what is recorded, what the design can estimate, and what remains unknown. In this study, that distinction prevents participant counts or safety listings from being treated as evidence of comparative efficacy.

15. Limitations

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

The most consequential limitation for interpreting efficacy is that the registry record does not report the primary response count, response proportion, or uncertainty interval. Although the endpoint definition and assessment timeframe are stated, the actual primary result cannot be evaluated. The record also does not report numerical results for either secondary outcome.

The single-group design has no randomized control arm. Outcomes in the study group cannot establish how the regimen compares with a control treatment, and effects of MK-3475 cannot be separated from the transplant and other recorded treatments. The registry’s rationale and investigators’ hypothesis describe why the study was proposed, but they are not substitutes for comparative results.

Participant accounting also leaves analytical questions. The record reports 32 enrolled, 29 treated, 26 evaluable for response, and 23 completing end-of-treatment response evaluation. It does not clearly state the denominator used for the primary estimate or how incomplete assessments were handled. It also does not report the primary analysis population, a missing-data approach, or sensitivity analyses.

Statistical analysis details—including a multiplicity plan, interim analysis plan, and sample-size justification—are not reported in the registry record. There is also a difference in dose wording: the arm description states 200 mg/day every 3 weeks, while the brief summary describes 200 mg intravenously every 3 weeks. The record does not resolve that wording. Finally, the safety summary does not provide detailed timing, recurrence, or event relatedness, limiting causal interpretation of adverse-event counts.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase 2 Multi-center Study of Anti-PD-1 During Lymphopenic State After HDT/ASCT for Multiple Myeloma — NCT02331368.
• Registry record last updated 2018-07-27; status last verified 2018-07.
• Results first posted 2018-07-27.
• 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.

19. Record Summary

NCT02331368 is a completed phase 2, multicenter, single-group study sponsored by the University of Michigan Rogel Cancer Center. It enrolled 32 participants with multiple myeloma and evaluated MK-3475 after high-dose chemotherapy and autologous stem cell transplantation, alongside lenalidomide maintenance as described in the registry. The primary endpoint was complete response at 180 days post-transplant.

The registry reports 29 treated participants, 26 evaluable for response, and 23 completing end-of-treatment response evaluation. It does not report the number of complete responders or the response estimate. Secondary outcomes concerned survival without relapse or progression and survival at 2 years, but their numerical results are not reported in the registry record. The safety summary lists 14 participants with serious adverse events, 30 with other adverse events, and no deaths among 32 at risk. Because the study had no control group, efficacy and safety results are descriptive rather than randomized comparisons.