Trial Outcomes & Findings for Nivolumab With or Without Varlilumab in Treating Patients With Relapsed or Refractory Aggressive B-cell Lymphomas (NCT NCT03038672)

Last Updated: 2025-11-10

Results Overview

Will be assessed by computed tomography (CT)-based criteria or positron emission tomography (PET)-CT based criteria. A response will be defined as an objective status of partial remission (PR) or complete remission (CR) for patients evaluated by CT-based criteria and complete metabolic response (CMR) or partial metabolic response (PMR) for patients evaluated by PET-CT based criteria. Exact binomial ninety-five percent confidence intervals for the true success proportion will be calculated in each arm. Comparison of overall response rates between the two treatment groups will be performed using a one-sided Fisher's exact test at significance level 0.15.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

54 participants

Primary outcome timeframe

2 years

Results posted on

2025-11-10

Participant Flow

Participant milestones

Participant milestones
Measure	Group I (Nivolumab) Patients receive nivolumab IV over 30 minutes every 2 weeks for 4 months and every 4 weeks for a total of up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may cross over to Group II at the time of disease progression.	Group II (Varlilumab, Nivolumab) Patients receive varlilumab IV over 90 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also receive nivolumab IV over 30 minutes every 2 weeks for 4 months and every 4 weeks for a total of up to 2 years in the absence of disease progression or unacceptable toxicity.
Initial Treatment STARTED	27	27
Initial Treatment COMPLETED	25	26
Initial Treatment NOT COMPLETED	2	1
Cross Over From Group I to Group II STARTED	7	26
Cross Over From Group I to Group II COMPLETED	7	26
Cross Over From Group I to Group II NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Group I (Nivolumab) Patients receive nivolumab IV over 30 minutes every 2 weeks for 4 months and every 4 weeks for a total of up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may cross over to Group II at the time of disease progression.	Group II (Varlilumab, Nivolumab) Patients receive varlilumab IV over 90 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also receive nivolumab IV over 30 minutes every 2 weeks for 4 months and every 4 weeks for a total of up to 2 years in the absence of disease progression or unacceptable toxicity.
Initial Treatment Unacceptable chemistry	0	1
Initial Treatment Progression prior to treatment	1	0
Initial Treatment No treatment per protocol	1	0

Baseline Characteristics

Nivolumab With or Without Varlilumab in Treating Patients With Relapsed or Refractory Aggressive B-cell Lymphomas

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group I (Nivolumab) n=27 Participants Patients receive nivolumab IV over 30 minutes every 2 weeks for 4 months and every 4 weeks for a total of up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may cross over to Group II at the time of disease progression.	Group II (Varlilumab, Nivolumab) n=27 Participants Patients receive varlilumab IV over 90 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also receive nivolumab IV over 30 minutes every 2 weeks for 4 months and every 4 weeks for a total of up to 2 years in the absence of disease progression or unacceptable toxicity.	Total n=54 Participants Total of all reporting groups
Age, Continuous	67 years n=5 Participants	69 years n=20 Participants	67.5 years n=40 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	7 Participants n=20 Participants	15 Participants n=40 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	20 Participants n=20 Participants	39 Participants n=40 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=20 Participants	1 Participants n=40 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	27 Participants n=5 Participants	24 Participants n=20 Participants	51 Participants n=40 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	2 Participants n=20 Participants	2 Participants n=40 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants
Race (NIH/OMB) White	27 Participants n=5 Participants	24 Participants n=20 Participants	51 Participants n=40 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	3 Participants n=20 Participants	3 Participants n=40 Participants

PRIMARY outcome

Timeframe: 2 years

Population: All eligible patients that had a disease evaluation after being treated.

Outcome measures

Outcome measures
Measure	Group I (Nivolumab) n=25 Participants Patients receive nivolumab IV over 30 minutes every 2 weeks for 4 months and every 4 weeks for a total of up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may cross over to Group II at the time of disease progression.	Group II (Varlilumab, Nivolumab) n=26 Participants Patients receive varlilumab IV over 90 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also receive nivolumab IV over 30 minutes every 2 weeks for 4 months and every 4 weeks for a total of up to 2 years in the absence of disease progression or unacceptable toxicity.
Overall Response Rate	0.16 proportion of participants Interval 0.045 to 0.361	0.08 proportion of participants Interval 0.01 to 0.251

SECONDARY outcome

Timeframe: 2 years

Population: All eligible and treated patients that achieve a response.

Defined as the date at which the patient's objective status is first noted to be a PR or CR for patients evaluated by CT-based criteria or CMR or PMR for patients evaluated by PET-CT based criteria to the earliest date progression (documentation of disease progression \[PMD\] or progressive disease \[PD\]) is documented. The distribution of duration of response will be estimated using the method of Kaplan-Meier. The comparison of duration of response between two treatment arms will be based on the log-rank test.

Outcome measures

Outcome measures
Measure	Group I (Nivolumab) n=4 Participants Patients receive nivolumab IV over 30 minutes every 2 weeks for 4 months and every 4 weeks for a total of up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may cross over to Group II at the time of disease progression.	Group II (Varlilumab, Nivolumab) n=2 Participants Patients receive varlilumab IV over 90 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also receive nivolumab IV over 30 minutes every 2 weeks for 4 months and every 4 weeks for a total of up to 2 years in the absence of disease progression or unacceptable toxicity.
Duration of Response	NA years Due to a lack of events the median and confidence intervals cannot be determined.	0.2 years Interval 0.2 to Due to a lack of events the upper confidence interval cannot be determined.

SECONDARY outcome

Timeframe: 37 months

Population: All eligible and treated patients.

The distribution of survival time will be estimated using the method of Kaplan-Meier. The comparison of overall survival between two treatment arms will be based on the log-rank test.

Outcome measures

Outcome measures
Measure	Group I (Nivolumab) n=25 Participants Patients receive nivolumab IV over 30 minutes every 2 weeks for 4 months and every 4 weeks for a total of up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may cross over to Group II at the time of disease progression.	Group II (Varlilumab, Nivolumab) n=26 Participants Patients receive varlilumab IV over 90 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also receive nivolumab IV over 30 minutes every 2 weeks for 4 months and every 4 weeks for a total of up to 2 years in the absence of disease progression or unacceptable toxicity.
Overall Survival	8.6 Months Interval 4.7 to Due to a lack of events the upper limit was not reached.	10.2 Months Interval 3.1 to Due to a lack of events the upper limit was not reached.

SECONDARY outcome

Timeframe: 37 months

Population: All eligible and treated patients that had a disease evaluation.

The distribution of PFS will be estimated using the method of Kaplan-Meier. The comparison of progression-free survival between two treatment arms will be based on the log-rank test.

Outcome measures

Outcome measures
Measure	Group I (Nivolumab) n=25 Participants Patients receive nivolumab IV over 30 minutes every 2 weeks for 4 months and every 4 weeks for a total of up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may cross over to Group II at the time of disease progression.	Group II (Varlilumab, Nivolumab) n=24 Participants Patients receive varlilumab IV over 90 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also receive nivolumab IV over 30 minutes every 2 weeks for 4 months and every 4 weeks for a total of up to 2 years in the absence of disease progression or unacceptable toxicity.
Progression Free Survival (PFS)	2.6 Months Interval 1.5 to 3.2	1.5 Months Interval 1.1 to 3.2

SECONDARY outcome

Timeframe: 25 months

Population: All eligible and treated patients.

Will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The overall adverse event rates for grade 3 or higher hematologic and non-hematologic adverse events at least possibly related to treatment will be compared between the two treatment groups using the Chi-square test (or Fisher's exact test if the data in the contingency table is sparse).

Outcome measures

Outcome measures
Measure	Group I (Nivolumab) n=25 Participants Patients receive nivolumab IV over 30 minutes every 2 weeks for 4 months and every 4 weeks for a total of up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may cross over to Group II at the time of disease progression.	Group II (Varlilumab, Nivolumab) n=26 Participants Patients receive varlilumab IV over 90 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also receive nivolumab IV over 30 minutes every 2 weeks for 4 months and every 4 weeks for a total of up to 2 years in the absence of disease progression or unacceptable toxicity.
Proportion of Patients With Grade 3 or Higher Adverse Events	0.76 proportion of patients	0.84 proportion of patients

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 100 days after last dose of study drug

Will be assessed by immunohistochemistry. Will be both graphically and quantitatively summarized and explored. Standard paired comparisons methodologies (Wilcoxon signed rank and McNemar's tests) will be used to assess changes in these variables before and after therapy. In addition, baseline values and changes over time in each measure will be explored in relation to clinical outcome. Differences between responders and non-responders will be assessed using Wilcoxon's rank sum (continuous data) or Fisher's exact (categorical data) test. The relationship between each measure and time to event measures (PFS, overall survival \[OS\]) will be evaluated using Cox's proportional hazards models and log-rank tests. Logistic regression will be used to model the response rate as a function of treatment and CD27 (as a continuous variable). The distribution of CD27 will be estimated empirically in the entire trial population and used to calculate CD27 values corresponding to each fixed percentile.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 12 weeks

Will be assessed by cytometry by time of flight (CyTOF). The relationship between presence/absence of a particular subtype of cell and association with outcomes will be evaluated. Evaluation of particular combinations of immune cells (immune signature) and whether they are predictive of outcome will also be evaluated. Will be both graphically and quantitatively summarized and explored. Standard paired comparisons methodologies (Wilcoxon signed rank and McNemar's tests) will be used to assess changes in these variables before and after therapy. In addition, baseline values and changes over time in each measure will be explored in relation to clinical outcome. Differences between responders and non-responders will be assessed using Wilcoxon's rank sum (continuous data) or Fisher's exact (categorical data) test. The relationship between each measure and time to event measures (PFS, OS) will be evaluated using Cox's proportional hazards models and log-rank tests.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to time of disease progression

Will be assessed by immunohistochemistry and CyTOF. Will be both graphically and quantitatively summarized and explored. Standard paired comparisons methodologies (Wilcoxon signed rank and McNemar's tests) will be used to assess changes in these variables before and after therapy. In addition, baseline values and changes over time in each measure will be explored in relation to clinical outcome. Differences between responders and non-responders will be assessed using Wilcoxon's rank sum (continuous data) or Fisher's exact (categorical data) test. The relationship between each measure and time to event measures (PFS, OS) will be evaluated using Cox's proportional hazards models and log-rank tests.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to time of disease progression

Will be assessed by fluorescence in situ hybridization. The proportion of patients in each of these groups who achieve a response will be evaluated. Will be both graphically and quantitatively summarized and explored. Standard paired comparisons methodologies (Wilcoxon signed rank and McNemar's tests) will be used to assess changes in these variables before and after therapy. In addition, baseline values and changes over time in each measure will be explored in relation to clinical outcome. Differences between responders and non-responders will be assessed using Wilcoxon's rank sum (continuous data) or Fisher's exact (categorical data) test. The relationship between each measure and time to event measures (PFS, OS) will be evaluated using Cox's proportional hazards models and log-rank tests.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 12 weeks

Will be assessed by enzyme-linked immunosorbent assay. Will be both graphically and quantitatively summarized and explored. Standard paired comparisons methodologies (Wilcoxon signed rank and McNemar's tests) will be used to assess changes in these variables before and after therapy. In addition, baseline values and changes over time in each measure will be explored in relation to clinical outcome. Differences between responders and non-responders will be assessed using Wilcoxon's rank sum (continuous data) or Fisher's exact (categorical data) test. The relationship between each measure and time to event measures (PFS, OS) will be evaluated using Cox's proportional hazards models and log-rank tests.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to time of disease progression

Will be assessed by whole exome sequencing. Will be both graphically and quantitatively summarized and explored. Standard paired comparisons methodologies (Wilcoxon signed rank and McNemar's tests) will be used to assess changes in these variables before and after therapy. In addition, baseline values and changes over time in each measure will be explored in relation to clinical outcome. Differences between responders and non-responders will be assessed using Wilcoxon's rank sum (continuous data) or Fisher's exact (categorical data) test. The relationship between each measure and time to event measures (PFS, OS) will be evaluated using Cox's proportional hazards models and log-rank tests.

Outcome measures

Outcome data not reported

Adverse Events

Group I (Nivolumab)

Serious events: 10 serious events

Other events: 24 other events

Deaths: 3 deaths

Group II (Varlilumab, Nivolumab)

Serious events: 12 serious events

Other events: 24 other events

Deaths: 5 deaths

Cross Over to Group II Treatment (Varlilumab, Nivolumab)

Serious events: 3 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Stephen Ansell

Mayo Clinic

Phone: (507)284-5096

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Group I (Nivolumab) n=27 participants at risk Patients receive nivolumab IV over 30 minutes every 2 weeks for 4 months and every 4 weeks for a total of up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may cross over to Group II at the time of disease progression.	Group II (Varlilumab, Nivolumab) n=27 participants at risk Patients receive varlilumab IV over 90 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also receive nivolumab IV over 30 minutes every 2 weeks for 4 months and every 4 weeks for a total of up to 2 years in the absence of disease progression or unacceptable toxicity.	Cross Over to Group II Treatment (Varlilumab, Nivolumab) n=7 participants at risk Pre cross over patients receive nivolumab IV over 30 minutes every 2 weeks for 4 months and every 4 weeks for a total of up to 2 years in the absence of disease progression or unacceptable toxicity. Patients may cross over to Group II at the time of disease progression. Post cross over patients receive varlilumab IV over 90 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also receive nivolumab IV over 30 minutes every 2 weeks for 4 months and every 4 weeks for a total of up to 2 years in the absence of disease progression or unacceptable toxicity.
Gastrointestinal disorders Gastric ulcer	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	0.00% 0/7 • 25 months for adverse events and 37 months for mortality
Gastrointestinal disorders Lower gastrointestinal hemorrhage	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	0.00% 0/7 • 25 months for adverse events and 37 months for mortality
Gastrointestinal disorders Nausea	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	0.00% 0/7 • 25 months for adverse events and 37 months for mortality
Gastrointestinal disorders Upper gastrointestinal hemorrhage	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	14.3% 1/7 • Number of events 1 • 25 months for adverse events and 37 months for mortality
Gastrointestinal disorders Vomiting	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	0.00% 0/7 • 25 months for adverse events and 37 months for mortality
General disorders Chills	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	0.00% 0/7 • 25 months for adverse events and 37 months for mortality
General disorders Edema limbs	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	0.00% 0/7 • 25 months for adverse events and 37 months for mortality
General disorders Fever	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	0.00% 0/7 • 25 months for adverse events and 37 months for mortality
General disorders Gen disord and admin site conds-Oth spec	7.4% 2/27 • Number of events 2 • 25 months for adverse events and 37 months for mortality	7.4% 2/27 • Number of events 2 • 25 months for adverse events and 37 months for mortality	0.00% 0/7 • 25 months for adverse events and 37 months for mortality
General disorders Malaise	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	14.3% 1/7 • Number of events 1 • 25 months for adverse events and 37 months for mortality
General disorders Pain	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	0.00% 0/7 • 25 months for adverse events and 37 months for mortality
Immune system disorders Immune system disorders - Other, specify	7.4% 2/27 • Number of events 2 • 25 months for adverse events and 37 months for mortality	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	0.00% 0/7 • 25 months for adverse events and 37 months for mortality
Infections and infestations Infections and infestations - Oth spec	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	0.00% 0/7 • 25 months for adverse events and 37 months for mortality
Infections and infestations Lung infection	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	0.00% 0/7 • 25 months for adverse events and 37 months for mortality
Injury, poisoning and procedural complications Fall	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	0.00% 0/7 • 25 months for adverse events and 37 months for mortality
Injury, poisoning and procedural complications Infusion related reaction	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	0.00% 0/7 • 25 months for adverse events and 37 months for mortality
Investigations Alanine aminotransferase increased	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	3.7% 1/27 • Number of events 2 • 25 months for adverse events and 37 months for mortality	0.00% 0/7 • 25 months for adverse events and 37 months for mortality
Investigations Platelet count decreased	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	0.00% 0/7 • 25 months for adverse events and 37 months for mortality
Metabolism and nutrition disorders Hypercalcemia	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	14.3% 1/7 • Number of events 1 • 25 months for adverse events and 37 months for mortality
Metabolism and nutrition disorders Hypokalemia	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	0.00% 0/7 • 25 months for adverse events and 37 months for mortality
Metabolism and nutrition disorders Hyponatremia	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	0.00% 0/7 • 25 months for adverse events and 37 months for mortality
Metabolism and nutrition disorders Tumor lysis syndrome	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	0.00% 0/7 • 25 months for adverse events and 37 months for mortality
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	0.00% 0/7 • 25 months for adverse events and 37 months for mortality
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, mal, uncpec - Oth spec	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	7.4% 2/27 • Number of events 2 • 25 months for adverse events and 37 months for mortality	0.00% 0/7 • 25 months for adverse events and 37 months for mortality
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	0.00% 0/7 • 25 months for adverse events and 37 months for mortality
Nervous system disorders Dizziness	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	14.3% 1/7 • Number of events 1 • 25 months for adverse events and 37 months for mortality
Nervous system disorders Intracranial hemorrhage	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	0.00% 0/7 • 25 months for adverse events and 37 months for mortality
Renal and urinary disorders Acute kidney injury	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	0.00% 0/7 • 25 months for adverse events and 37 months for mortality
Renal and urinary disorders Renal calculi	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	0.00% 0/7 • 25 months for adverse events and 37 months for mortality
Respiratory, thoracic and mediastinal disorders Hypoxia	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	0.00% 0/7 • 25 months for adverse events and 37 months for mortality
Respiratory, thoracic and mediastinal disorders Pleural effusion	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	0.00% 0/7 • 25 months for adverse events and 37 months for mortality
Respiratory, thoracic and mediastinal disorders Pneumonitis	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	0.00% 0/7 • 25 months for adverse events and 37 months for mortality
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	0.00% 0/7 • 25 months for adverse events and 37 months for mortality
Vascular disorders Hematoma	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	0.00% 0/7 • 25 months for adverse events and 37 months for mortality
Vascular disorders Hypotension	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	14.3% 1/7 • Number of events 1 • 25 months for adverse events and 37 months for mortality
Vascular disorders Thromboembolic event	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	0.00% 0/7 • 25 months for adverse events and 37 months for mortality
Blood and lymphatic system disorders Anemia	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	0.00% 0/7 • 25 months for adverse events and 37 months for mortality
Cardiac disorders Atrial fibrillation	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	14.3% 1/7 • Number of events 1 • 25 months for adverse events and 37 months for mortality
Cardiac disorders Sinus tachycardia	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	14.3% 1/7 • Number of events 1 • 25 months for adverse events and 37 months for mortality
Eye disorders Blurred vision	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	0.00% 0/7 • 25 months for adverse events and 37 months for mortality
Gastrointestinal disorders Abdominal pain	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	28.6% 2/7 • Number of events 2 • 25 months for adverse events and 37 months for mortality
Gastrointestinal disorders Gastric hemorrhage	3.7% 1/27 • Number of events 1 • 25 months for adverse events and 37 months for mortality	0.00% 0/27 • 25 months for adverse events and 37 months for mortality	0.00% 0/7 • 25 months for adverse events and 37 months for mortality