Study of Magrolimab Combinations in Patients With Relapsed/Refractory Multiple Myeloma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Magrolimab Combinations in Patients With Relapsed/Refractory Multiple Myeloma (NCT04892446), a non-randomized phase 2 study. The primary outcome is Percentage of Participants Experiencing Dose-limiting Toxicities (DLTs) According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.

2. Clinical Question

3. Trial Design

This was a phase 2, multi-arm study of magrolimab combinations in participants with relapsed/refractory multiple myeloma. The study used non-randomized allocation, no masking, and a sequential model. These features mean that the combination groups should be read as cohorts within a study, not as randomized treatment and control arms. The registry lists an enrollment of 36.

The listed regimens paired magrolimab with daratumumab, pomalidomide and dexamethasone, carfilzomib and dexamethasone, or bortezomib and dexamethasone. The record indicates that the bortezomib combination could be initiated based on preliminary safety and efficacy in the carfilzomib cohort. The treatment descriptions also distinguish prior-treatment requirements across cohorts. The record does not provide enough detail to reconstruct the full sequence of cohort decisions or the complete dosing schedules.

The study start date is 2021-11-09, and the listed primary completion date is 2024-04-25. Its status is terminated. The registry record does not report the reason for termination, so the status alone does not explain why the study ended or what prompted that decision. Nor does the listed primary completion date establish that every planned activity or analysis was completed.

The study's stated goal was to learn about safety and dosing. Its primary endpoint focused on dose-limiting toxicities during a defined assessment period, rather than directly comparing efficacy between randomized groups. The registry record does not report a randomized comparison, a protocol rationale for the enrollment target, or a detailed statistical analysis plan.

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: Participants were enrolled at study sites in the United States, Czech Republic, and Canada. Magrolimab in combination with bortezomib and dexamethasone cohort was not initiated due to early closure of study. As all participants were dosed with same dose of magrolimab, per prespecified analysis, data for Safety Run-in and corresponding Dose-expansion cohorts were combined except for dose limiting toxicity outcome measure, for which data was collected only in Safety Run-in Cohorts.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The DLT-Evaluable Analysis Set included all participants in the Safety Analysis Set who were enrolled in the Safety Run-in cohorts and fulfilled the criteria for evaluation for DLT specified in the protocol.

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: The Safety Analysis Set included all participants who received at least 1 dose of study treatment with treatment group designated according to the actual treatment received. As all participants were dosed with same dose of magrolimab, per prespecified analysis, data for Safety Run-in and corresponding Dose-expansion cohorts were combined for all 3 arms.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Experiencing Dose-limiting Toxicities (DLTs) According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, measured over Up to 35 days.

The primary endpoint was the percentage of participants experiencing dose-limiting toxicities, or DLTs, according to NCI CTCAE version 5.0. The assessment period was up to 35 days. A DLT was defined as a hematologic or nonhematologic toxicity at Grade 3 or higher that had worsened from pretreatment baseline during that period and that, in the investigator's opinion, was at least possibly related to magrolimab.

This kind of endpoint is used in safety and dose-finding work to identify clinically important toxicities within a specified early assessment window. It focuses attention on events that meet prespecified severity, timing, change-from-baseline, and attribution criteria. It does not count every adverse event as a DLT: an event must satisfy the definition, including the investigator's judgment about its relation to magrolimab.

The stated analysis population was the DLT-Evaluable Analysis Set: participants in the Safety Analysis Set who were enrolled in Safety Run-in cohorts and met protocol criteria for DLT evaluation. This is not necessarily the same population as all enrolled participants or all participants represented in the adverse-event summaries. The registry record does not report the primary endpoint's event count, denominator, percentage, or uncertainty estimate. Therefore, the posted record does not establish the observed DLT percentage.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a percentage endpoint represent?

For a binary outcome such as whether a participant experienced a DLT, a percentage describes the share of a defined analysis population with the event. Its meaning depends on both the event definition and the denominator. Here, the denominator is not simply everyone enrolled: the registry defines the DLT-Evaluable Analysis Set using Safety Analysis Set membership, enrollment in Safety Run-in cohorts, and protocol evaluation criteria. The primary endpoint result is not reported, so neither the observed percentage nor its precision can be assessed.

Why does the DLT definition matter?

A toxicity contributes to this endpoint only if it meets the stated criteria. It must be Grade 3 or higher, worsen from pretreatment baseline during the assessment period, and be considered at least possibly related to magrolimab by the investigator. This is narrower than counting all adverse events or all serious adverse events. Seriousness and severity are related but distinct classifications: an event can be serious for reasons that do not make it a qualifying DLT, and a qualifying DLT is not identified solely by appearing in a serious-event summary.

How should uncertainty be assessed?

General statistical principle: an estimate from a binary endpoint has sampling uncertainty, and a confidence interval expresses a range of values compatible with the observed data under the method's assumptions. The interval's width depends in part on the amount of information in the analysis population and the number of events. Without the endpoint's numerator and denominator, there is no estimate or interval to interpret. The registry record does not report a confidence interval for this endpoint.

General statistical principle: when event counts are limited, estimates can be imprecise, and conventional approximations may not perform well. The methods used for an interval or test should match the data and the study design. The registry record does not describe an inferential method for the primary endpoint. It would therefore be inappropriate to infer a significance test, a precision estimate, or a model from the endpoint definition alone.

What does the design permit?

Non-randomized cohorts do not have the protection against confounding that random allocation can offer. The sequential model also means cohorts were not necessarily assessed concurrently under identical conditions. General statistical principle: a difference between observed cohort summaries can reflect treatment differences, participant characteristics, timing, or other factors. Without a randomized comparison or a reported adjustment strategy, cohort-level contrasts are descriptive rather than causal.

The study is also unmasked. That is a design feature to consider when reading outcomes that involve judgment, such as investigator attribution of an event to magrolimab. The registry record does not report additional procedures used to reduce assessment bias, so none should be assumed.

How are the planning assumptions different from trial results?

The registry describes a sample-size planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is described as a fraction of the observed effect. For time-to-event outcomes, the stated illustration uses a total number of events, while other outcomes use participants per arm. These are planning conventions, not observed trial outcomes or observed power. The registry record does not report numerical planning outputs in the information summarized for this study, and the illustration is not the study's own design justification.

What can be learned from the adverse-event counts?

The listed counts show how many participants were recorded as affected within each reported group and how many were at risk in that summary. Such counts are descriptive. They are not adjusted for differences across cohorts, do not establish event timing, and do not identify causality. The serious-event terms and percentages are also descriptive listings; the registry record does not provide enough information to infer a common follow-up period or a comparative rate model for those terms.

Recalculated comparisons are not available in the registry record. In particular, there are no reported primary endpoint results from which to recalculate a DLT percentage or compare it with another arm. The sponsor's own analysis cannot be assessed from this record because no primary endpoint analysis is posted. General statistical principle: any reanalysis of summary counts would remain unadjusted and would not replace a prespecified sponsor analysis.

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("Magrolimab+Daratumumab", "Magrolimab+Pomalidomide+Dexamethasone", "Magrolimab+Carfilzomib+Dexamethasone")
n      <- c(6, 6, 6)
events <- c(1, 1, 0)
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  Magrolimab+Daratumumab  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9
ARM  Magrolimab+Pomalidomide+Dexamethasone  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9
ARM  Magrolimab+Carfilzomib+Dexamethasone  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0

11. Multiplicity, Missing Data and Analysis Populations

The record lists secondary outcomes including duration of response, serum concentration of magrolimab, and the percentage of participants with positive anti-magrolimab antibodies. It also reports 7 outcome measures, but lists no analyses. The registry record does not report how the primary and secondary outcomes were ordered for inference, whether any multiplicity adjustment was planned, or which outcomes were intended to support formal confirmatory claims.

General statistical principle: when several outcomes or comparisons are tested, the chance of at least one apparently unusual result can increase unless the analysis plan accounts for multiple testing. A prespecified hierarchy or adjustment can help control that issue. Neither an adjustment nor a testing hierarchy is reported, so the secondary outcomes should be treated as descriptive unless further analysis information is available.

The record does not report how missing outcome data were handled, what follow-up was required for each analysis, or whether participants with incomplete assessments were excluded or otherwise accounted for. It also does not report imputation methods or sensitivity analyses. These details matter because missing observations can affect both the denominator and the interpretation of a percentage endpoint.

The primary population is defined as the DLT-Evaluable Analysis Set, drawn from the Safety Analysis Set and restricted to Safety Run-in cohorts meeting protocol criteria. The registry record does not report the number meeting those criteria or explain how participants who did not meet them were handled in other outcomes. Definitions of analysis populations for the secondary outcomes are not reported in the registry record. The posted information therefore does not permit a full assessment of missing-data assumptions, population selection, or multiplicity control.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (18.2%), febrile neutropenia (10.0%), acute sinusitis (10.0%), covid-19 pneumonia (10.0%), febrile infection (10.0%).

The serious adverse-event summaries list participants at risk and participants affected in three combination groups. Serious adverse events affected 5 of 14 participants receiving magrolimab plus daratumumab, 5 of 10 receiving magrolimab plus pomalidomide and dexamethasone, and 4 of 11 receiving magrolimab plus carfilzomib and dexamethasone. The record lists deaths as 4, 4, and 0 in those same groups. It does not give a death cause or attribute those deaths to treatment in these summaries.

The record also lists other adverse events affecting 14 of 14 participants, 10 of 10 participants, and 11 of 11 participants in those groups, respectively. These counts do not indicate severity, duration, or relation to study drugs. The serious-event terms include pneumonia at 18.2%, and febrile neutropenia, acute sinusitis, Covid-19 pneumonia, febrile infection, and Klebsiella urinary tract infection at 10.0% each. The record does not provide enough denominator or follow-up detail alongside these terms to interpret them as comparative risks.

These safety summaries are not the primary DLT result. They do not establish whether events met the DLT definition or were judged related to magrolimab. Because the cohorts were non-randomized, the counts should not be used as a like-for-like ranking of combinations.

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

The record establishes that this was a phase 2, non-randomized study of magrolimab combinations in relapsed/refractory multiple myeloma, designed with a stated focus on safety and dosing. It defines the primary safety endpoint and reports selected adverse-event information for three combination groups. It does not report the primary endpoint result, so the rate of DLTs in the DLT-Evaluable Analysis Set cannot be stated from the registry record.

The reported serious adverse-event counts and affected-participant counts describe events recorded in the listed groups. They do not by themselves show that magrolimab caused those events, that all events occurred during the DLT assessment period, or that they met the primary endpoint definition. The listed deaths likewise have no stated cause or treatment attribution in these summaries. The record does not provide a like-for-like randomized comparison that would support attributing differences between groups to their treatments.

The study's terminated status does not explain why it was terminated. The registry record does not report the reason, nor does the status alone establish whether the decision was related to safety, efficacy, operational issues, or another cause. The listed primary completion date is 2024-04-25, but the record does not provide the primary endpoint analysis.

Accordingly, the registry information supports a description of design, endpoint definitions, and selected safety counts, but not a quantitative conclusion about the primary DLT endpoint or a causal comparison among combinations. It also does not establish whether the combinations are effective or ineffective. Such conclusions would require results and analyses that are not reported in the registry record.

14. Why This Trial Matters Statistically

This study illustrates why the endpoint definition and the analysis population need to be read together. A DLT is not simply any adverse event: it must satisfy the stated severity, worsening-from-baseline, timing, and investigator-attribution conditions. The primary endpoint also applies to a specifically defined DLT-Evaluable Analysis Set rather than automatically to every enrolled participant. Without the event count and denominator for that population, the endpoint cannot be interpreted as a percentage.

The design is statistically important as well. Non-randomized, sequential cohorts can provide descriptive safety information, but they do not create the balance of a randomized comparison. Apparent differences across combinations may reflect differences in participants, prior treatment, cohort timing, or other factors. The conditional introduction of the bortezomib combination further underscores that the cohorts were not necessarily formed as parallel, directly comparable groups.

Finally, the record includes selected adverse-event counts but no posted analyses and no primary endpoint result. This distinction matters: descriptive safety summaries can inform what was recorded, but they cannot substitute for a defined endpoint analysis, uncertainty estimates, or a causal comparison. The terminated status is also a context point, not an explanation of the study's results. The registry record does not report why the study was terminated. Together, these features make careful separation of observed summaries, endpoint results, and causal interpretation essential.

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 important limitation for interpreting the primary question is that the registry record does not report the DLT endpoint's numerator, denominator, percentage, or uncertainty estimate. The endpoint definition and analysis population are available, but the primary outcome itself is not. The record also lists no analyses, limiting assessment of how outcomes were evaluated.

The study was non-randomized, unmasked, and sequential. These design features limit direct comparisons among combination groups and leave potential for differences in participant characteristics, timing, and outcome assessment to influence observed summaries. The registry record does not report an adjustment strategy or a concurrent randomized comparator.

The adverse-event information is incomplete for causal interpretation. The listed summaries do not specify whether deaths were related to treatment, provide event-level timing, or link serious events to the DLT assessment period and definition. The record does not report enough detail to interpret the listed serious-event percentages as comparative rates with a common follow-up period.

The registry record does not explain the reason for termination. It also does not report the rationale for the enrollment target, detailed missing-data handling, multiplicity procedures, or the analysis populations for secondary outcomes. These omissions constrain evaluation of precision, selection, and the scope of any formal claims. The available information supports a descriptive account, not a complete assessment of the study's planned or final statistical analyses.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of Magrolimab Combinations in Patients With Relapsed/Refractory Multiple Myeloma — NCT04892446.
• Registry record last updated 2025-05-02; status last verified 2025-04.
• Results first posted 2025-05-02.
• 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

NCT04892446 is a phase 2, multi-arm study of magrolimab combinations in relapsed/refractory multiple myeloma. It used non-randomized allocation, no masking, and a sequential model. The listed enrollment is 36, and the status is terminated. The primary endpoint was the percentage of DLT-evaluable participants experiencing qualifying toxicities during an assessment period of up to 35 days.

The registry record lists serious and other adverse-event counts for the daratumumab, pomalidomide and dexamethasone, and carfilzomib and dexamethasone combinations. It does not report the primary endpoint result, formal analyses, or the reason for termination. Consequently, the posted information supports descriptive reading of the listed safety summaries but not a quantitative interpretation of the primary endpoint or causal comparisons among combinations.