This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Radiotherapy With Immunotherapy for Systemic Effect in Myeloma (RISE-M) (NCT03634800), a na phase 2 study. The primary outcome is To Determine Overall Response at 12 Weeks Using International Myeloma Working Group (IMWG) Criteria in Patients Will be Measured.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03634800 |
| Phase | Phase 2 |
| Condition | Multiple Myeloma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 6 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Weill Medical College of Cornell University |
| Results posted | Yes |
2. Clinical Question
Population
Patients with multiple myeloma, measurable disease in the blood, and a targetable soft tissue or bony lesion suitable for radiotherapy were eligible. The record says 6 participants were enrolled; 5 started treatment, and only 3 reached 12 weeks of treatment.
Intervention
The treatment combined nivolumab and radiotherapy to a targetable lesion. Nivolumab was described as 240 mg intravenously every 2 weeks, starting with the first radiotherapy fraction. Radiotherapy was described as 6 Gy x 5 fractions.
Comparator
There was no concurrent comparison group: the study is listed as a single-group trial, with allocation recorded as NA. The registry record does not describe a control arm.
Primary question
The primary aim was to assess overall response at 12 weeks using International Myeloma Working Group criteria. The registry record describes the endpoint but does not report how many participants achieved a response.
The clinical question is therefore whether response at the specified assessment point could be estimated among participants receiving the combined regimen. This is a descriptive, early-phase question rather than a randomized comparison of treatment strategies. The record also lists median progression-free survival and median overall survival as secondary aims, but it does not report their results.
Interpretation must account for the small number who started treatment and the smaller number who reached the 12-week assessment. These are different stages in the participant flow, and the response question concerns the stated 12-week timepoint. The registry record does not explain why participants did not start or reach that assessment, nor does it give response counts for those who did.
3. Trial Design
RISE-M is listed as a phase 2 study of nivolumab with radiotherapy in multiple myeloma. It used a single-group model, with no masking and allocation recorded as NA. The record gives an enrollment of 6. These design details describe a study in which participants received the combination rather than being assigned between treatment groups. There is consequently no concurrent control group in the registry record against which to compare outcomes.
The intervention description specifies nivolumab 240 mg intravenously every 2 weeks, beginning with the first radiotherapy fraction, and radiotherapy of 6 Gy x 5 fractions to a targetable lesion. The brief summary says treatment would continue until disease progression or dose-limiting toxicity. Eligible participants were described as having measurable disease in the blood and a soft tissue or bony lesion that could be treated with radiotherapy.
The registered primary endpoint was overall response at 12 weeks, assessed using International Myeloma Working Group criteria. The record also names median progression-free survival and median overall survival as secondary outcomes. It gives no reported result for these secondary outcomes.
The study status is terminated. The registry record says that 5 patients started treatment and only 3 reached 12 weeks of treatment. It does not report why the trial was terminated, why the other participants did not start or reach the assessment, or whether the planned enrollment was achieved. Those details should not be inferred from the status alone.
A single-group design can describe what happened among treated participants, but it cannot isolate the effect of one component of a combined regimen or establish how outcomes would have differed under another treatment. The record does not report a statistical plan, a sample-size justification, interim analyses, or an analysis population definition.
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
| Stage | Nivolumab/Radiotherapy |
|---|---|
| STARTED | 6 |
| COMPLETED | 0 |
| NOT COMPLETED | 6 |
Reasons for not completing this period:
| Reason | Nivolumab/Radiotherapy |
|---|---|
| Adverse Event | 1 |
| Disease Progression | 4 |
| Withdrawal by Subject | 1 |
Analysis population for the primary outcome, as defined in the registry: Out of the 5 patients that started treatment, only 3 patient made it to 12 weeks of treatment.
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: 6 patients enrolled but 1 patient withdrew consent prior to starting treatment. 5 patients that enrolled and started treatment will be a part of the analysis population.
| Characteristic | Unit | Nivolumab/Radiotherapy |
|---|---|---|
| Participants analysed | 5 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 2 |
| Age, Categorical: >=65 years | Participants | 3 |
| Age, Continuous | years | 59.4 (26 to 72) |
| Sex: Female, Male: Female | Participants | 3 |
| Sex: Female, Male: Male | Participants | 2 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 3 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 1 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 3 |
| Race (NIH/OMB): More than one race | Participants | 2 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
6. Primary Endpoint
The registry lists the primary outcome as To Determine Overall Response at 12 Weeks Using International Myeloma Working Group (IMWG) Criteria in Patients Will be Measured, measured over 12 weeks.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint was overall response at 12 weeks, evaluated using International Myeloma Working Group criteria. The endpoint is intended to classify participants according to disease response at a defined assessment time. The registry description sets out categories including complete response, very good partial response, partial response, stable disease, and progressive disease, with definitions based on laboratory measurements and findings such as soft tissue plasmacytomas or bone lesions. The registered primary aim was to estimate overall response; the registry record does not report the resulting number of responders.
A response endpoint at a stated timepoint can provide a structured summary of disease status in an early-phase study. Applying prespecified clinical criteria can make the classification more consistent than an informal judgment. As a general statistical point, a fixed assessment time also makes clear when the outcome is being evaluated. It does not, by itself, describe how long a response lasts or what happens after that timepoint.
The record says only 3 patients made it to 12 weeks of treatment, out of 5 who started. This limits what can be learned from the stated assessment, particularly because the response count and handling of participants without a 12-week assessment are not reported in the registry record. The record does not say whether the endpoint was analyzed as a count, proportion, or another summary beyond identifying its measure as participants.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes an intended estimate of overall response at 12 weeks, but it does not post the response result. It therefore does not establish from the available record how many participants met the response criteria, how many had stable or progressive disease, or how uncertain any estimate would be. The endpoint description is not itself an outcome finding.
Participant flow is important to the interpretation. The record gives enrollment as 6, says 5 patients started treatment, and says only 3 reached 12 weeks of treatment. The registry does not explain the difference between enrollment and treatment start, or why some participants did not reach the 12-week point. It also does not report whether the response assessment was available for every participant who reached that point. Without these details, the analysis denominator and the treatment of missing assessments are unclear.
The design has no comparator group. Thus, even if a response result were reported, a single-group result would describe outcomes in this study but would not provide a randomized estimate of the difference between the combination and another treatment. Because the intervention includes both nivolumab and radiotherapy, the design also cannot distinguish their separate contributions.
The status is terminated, but the reason is not reported in the registry record. Termination alone does not explain whether enrollment, follow-up, feasibility, safety, or another consideration drove the decision. Likewise, the registered secondary aims for progression-free survival and overall survival should not be treated as results: the record lists those aims but does not report estimates.
The posted safety summary reports 2 participants with serious adverse events among 5 at risk, 5 with other adverse events among 5 at risk, and 2 deaths. These are descriptive figures in the registry record. The record does not state whether the deaths were related to treatment or provide enough context to interpret their causes. The listed serious-event terms each have a reported percentage, but their individual counts and timing are not given in the registry record.
Overall, the available information supports a cautious description of a small, terminated, single-group study with limited 12-week follow-up. It does not support a comparative efficacy conclusion, a precise response estimate, or a causal interpretation of safety events. Those limits arise from the unreported endpoint result, small participant flow, lack of a control group, and missing details about analysis and follow-up.
9. Statistical Methods Explained
What does a single-group design show?
The study is listed as single-group, with no masking and allocation recorded as NA. In a single-group study, the main outcome summary describes participants who received the study regimen. There is no concurrent control group in this record to show what would have happened over the same period under a different intervention. As a general statistical point, a comparison with an external expectation or historical experience is not equivalent to randomized allocation, because groups may differ in important ways.
Here, the intervention combines nivolumab and radiotherapy. A result in this design could not separate the contribution of one component from the other. Nor could it establish a treatment difference relative to an alternative. The design may be used to characterize outcomes and feasibility, but the registry record does not report its design rationale or a formal statistical plan.
How should the 12-week endpoint be understood?
The primary endpoint is overall response at 12 weeks under International Myeloma Working Group criteria. The registry description identifies response categories and includes disease measurements and findings used in those definitions. As a general concept, categorical endpoints classify each assessed participant into an outcome group according to stated rules. The clarity of the classification depends on applying the criteria consistently and reporting how unclassified or unavailable assessments are handled.
The record reports that only 3 patients made it to 12 weeks of treatment, out of 5 who started. It does not give the primary response count or explain whether all participants who reached 12 weeks were assessed. It also does not report how participants without an assessment were handled in the analysis. Without the numerator, denominator, and missing-outcome approach, a response proportion cannot be interpreted from the registry record.
What does a confidence interval communicate?
As a general statistical explanation, a confidence interval expresses the uncertainty around an estimate under the assumptions of the method used. A narrower interval indicates greater precision, while a wider interval indicates less precision. In a study with few observations, estimates can be imprecise, and an interval may span a broad range of plausible values. The registry record does not report a response estimate or confidence interval for this primary endpoint, so precision cannot be assessed.
A confidence interval would not remove design limitations. Even a precise single-group estimate would describe the observed group rather than establish a comparative treatment effect. Precision and causal interpretation are distinct issues: the former concerns uncertainty in an estimate, while the latter depends on the design and assumptions supporting a comparison.
What can be learned from the event counts?
The safety summary presents participants at risk and participants affected for serious and other adverse events, as well as deaths. As a general statistical point, event counts and the number of participants affected answer different questions. A participant may experience more than one event, so a count of affected participants should not be read as the total number of event occurrences. The registry record also does not provide timing, duration, severity grades beyond the serious-event grouping, or attribution for the reported deaths in the registry record.
The listed serious adverse event terms are accompanied by percentages. These are descriptive entries; without more details, they should not be interpreted as comparative rates or evidence that the regimen caused a particular event. The study has no control group, and the safety summary is based on the group described in the registry record.
How should planning illustrations be read?
Any sample-size figures shown elsewhere on the page are planning illustrations, not observed power and not the trial's own design justification. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. Time-to-event planning tables use the total number of events, while other planning tables use participants per arm.
These planning assumptions describe hypothetical future comparisons, not this trial's single-group design. The registry record does not report a sample-size justification, and a planning calculation cannot establish that this study was adequately sized for its primary aim. Because the primary response result is not reported, this page cannot use it to characterize an observed effect or its precision. Sample-size calculations should be read as design illustrations under their stated assumptions, not as a statement about the trial's achieved power or evidence of benefit.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists one primary aim, overall response at 12 weeks, and two secondary aims: median progression-free survival and median overall survival. It does not report a statistical analysis plan, a hierarchy for testing these outcomes, an adjustment for multiple comparisons, or whether any formal hypothesis tests were planned. The number of outcome measures and analyses recorded does not provide a substitute for those details.
As a general statistical point, examining multiple outcomes or analyses can increase the chance of a chance finding if each is treated as confirmatory. A prespecified hierarchy or multiplicity procedure can address that issue, but the registry record does not say whether one was used. No correction or testing strategy should be assumed.
Missingness is a substantial interpretive issue in the participant flow. The record says 6 were enrolled, 5 started treatment, and only 3 made it to 12 weeks of treatment. It does not report why participants did not start or reach the assessment, whether those who reached 12 weeks had evaluable response data, or how any unavailable endpoint assessments were treated. It does not report an analysis population such as all enrolled participants, all treated participants, or participants with an evaluable assessment.
As a general statistical point, missing outcomes can affect an estimate if the participants with missing assessments differ from those assessed. The direction and size of any such effect cannot be determined without further information. The posted record does not describe imputation, sensitivity analyses, or other missing-data methods. Consequently, the response result and the population to which it would apply cannot be reconstructed from the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Nivolumab/Radiotherapy | 2 | 5 | 40.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Nivolumab/Radiotherapy | 2 of 5 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Nivolumab/Radiotherapy | 5 of 5 |
Most frequent serious adverse event terms
| Event term | Organ system | Nivolumab/Radiotherapy |
|---|---|---|
| Platelet count decreased | Investigations | 1 of 5 |
| Anemia | Blood and lymphatic system disorders | 1 of 5 |
| Back pain | Musculoskeletal and connective tissue disorders | 1 of 5 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Nivolumab/Radiotherapy |
|---|---|---|
| Peripheral motor neuropathy | Nervous system disorders | 2 of 5 |
| Nausea | Gastrointestinal disorders | 1 of 5 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 1 of 5 |
| Back pain | Musculoskeletal and connective tissue disorders | 1 of 5 |
| Fatigue | General disorders | 1 of 5 |
| Myalgia | Musculoskeletal and connective tissue disorders | 1 of 5 |
| Bloating | Gastrointestinal disorders | 1 of 5 |
| bone pain | Musculoskeletal and connective tissue disorders | 1 of 5 |
| Vomiting | Gastrointestinal disorders | 1 of 5 |
| Diarrhea | Gastrointestinal disorders | 1 of 5 |
Serious events with the highest arm-level rate: platelet count decreased (20.0%), anemia (20.0%), back pain (20.0%).
The safety summary lists 5 participants at risk for serious adverse events, with 2 affected. For other adverse events, it lists 5 at risk and 5 affected. It also reports 2 deaths. These are participant-level figures in the registry summary; they should not be confused with a total count of all event occurrences.
The serious adverse event terms listed are platelet count decreased, anemia, and back pain, each with a reported percentage of 20.0%. The record does not provide the individual event counts, timing, duration, or additional clinical detail for those terms in the registry record. The reported percentages should therefore be read as the posted descriptive figures, not as comparative estimates.
The record does not state whether the deaths were considered related to treatment, nor does it give their causes in the information. It also does not provide a control group for comparison. As a general statistical point, adverse events observed during a study do not by themselves establish that the intervention caused them. These summaries describe what the registry record reports in a small treated group; they do not quantify comparative safety.
12. What the Result Does, and Does Not, Mean
The record documents a phase 2, single-group study of nivolumab combined with radiotherapy in multiple myeloma. It defines a primary response assessment at 12 weeks and describes the criteria intended for classifying response. It also reports a limited participant flow: 6 enrolled, 5 started treatment, and 3 reached 12 weeks of treatment. The posted safety summary includes serious and other adverse-event counts and deaths.
However, the primary response result is not reported in the registry record. The record therefore does not show how many participants responded, the denominator used for any response estimate, or the uncertainty around such an estimate. The listed secondary aims do not come with reported results. The termination status is reported, but its reason is not.
The study does not include a concurrent control group. As a result, its design cannot estimate a randomized difference between the combination and another treatment. It also cannot separate the contribution of nivolumab from the contribution of radiotherapy. These are limits on what the design can establish, not conclusions about the intervention itself.
The safety figures are descriptive and do not establish treatment causation. The registry record does not state whether deaths were related to treatment, and the available information does not provide the context needed to interpret their causes. Small participant flow and incomplete reporting further limit precision and interpretation.
In short, the record describes the trial question and some participant-flow and safety information, but it does not report the primary efficacy result or the statistical analyses needed to assess it. The findings should not be taken as proof for or against the regimen. They show what is documented in the registry record and what remains unreported.
13. Why This Trial Matters Statistically
This trial illustrates why a clearly defined endpoint is only one part of interpreting a clinical study. RISE-M identifies overall response at 12 weeks and describes response categories, but the registry record does not report the response result. Without that result, readers cannot assess the observed outcome or its precision, even though the endpoint itself is specified.
The participant flow also matters statistically. The record reports 6 enrolled, 5 who started treatment, and 3 who reached 12 weeks. When the numbers contributing at each stage differ, readers need to know the analysis population and how unavailable outcomes were handled. Those details are not reported in the registry record. This limits the ability to understand the primary endpoint estimate or to judge how representative it might be of all enrolled participants.
The single-group design provides no concurrent control comparison. This distinction is central: a descriptive outcome in a treated group is not a randomized estimate of a treatment effect. In a combination regimen, the same design also cannot isolate the effects of its separate components. These are general features of the design and do not depend on whether a particular outcome is favorable or unfavorable.
Finally, the record's termination status, safety summaries, and secondary aims all require careful reading. The reason for termination and secondary outcome results are not reported. The safety figures describe the registry's summary but do not establish causality. Together, these points show why statistical interpretation depends not only on endpoint definitions, but also on complete outcome reporting, participant accounting, and a design suited to the question being asked.
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.
Several limitations are specific to the record and study. First, the primary endpoint result is not reported in the registry record. Although the endpoint and its assessment time are described, the response count and analysis denominator are absent. No estimate or confidence interval can therefore be interpreted from the posted information.
Second, the registry reports 6 enrolled, 5 who started treatment, and only 3 who made it to 12 weeks. It does not explain these transitions, report the reasons participants did not start or reach the assessment, or describe how missing endpoint data were handled. The analysis population is not reported in the registry record.
Third, this was a single-group study with allocation recorded as NA and no masking. There is no concurrent control arm, so the study cannot provide a randomized comparison. Because nivolumab and radiotherapy were administered together, the design also cannot distinguish their individual contributions.
Fourth, the study is listed as terminated, but the reason is not reported in the registry record. The record also lists progression-free survival and overall survival as secondary aims without reporting their results. It does not report the statistical analysis plan, sample-size justification, interim analyses, multiplicity approach, or missing-data methods.
Finally, safety information is limited to the posted participant counts, deaths, and listed serious-event terms. Treatment attribution for deaths and further event details are not reported in the information. These limitations constrain both efficacy and safety interpretation.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Radiotherapy With Immunotherapy for Systemic Effect in Myeloma (RISE-M) — NCT03634800.
- Registry record last updated 2021-08-05; status last verified 2021-07.
- Results first posted 2021-08-05.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
RISE-M (NCT03634800) is listed as a phase 2, single-group trial of nivolumab with radiotherapy in multiple myeloma. The intervention description specifies nivolumab 240 mg intravenously every 2 weeks and radiotherapy of 6 Gy x 5 fractions to a targetable lesion. The study is listed as terminated.
The primary aim was overall response at 12 weeks using International Myeloma Working Group criteria. The record reports 6 enrolled, 5 who started treatment, and 3 who reached 12 weeks, but it does not report the primary response result. Progression-free survival and overall survival are listed as secondary aims without reported results.
The safety summary reports 2 of 5 participants affected by serious adverse events, 5 of 5 affected by other adverse events, and 2 deaths. The registry record does not report treatment attribution for the deaths. It also does not report a statistical analysis plan, sample-size justification, or reason for termination.