Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Antineoplastic Agents

All Drugs and Chemicals

Lenalidomide

Bortezomib

Pomalidomide

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Oral pomalidomide 4 mg on Days 1-21 of 28-day cycle until progressive disease (PD) or unacceptable toxicity

pomalidomide

Mohamed Zaki, MD, PhD

The purpose of this study is to evaluate the efficacy and safety of pomalidomide monotherapy in subjects with refractory or relapsed and refractory multiple myeloma who were enrolled in study CC-4047-MM-003 (NCT01311687) and discontinued treatment with high-dose dexamethasone due to disease progression.

Study to Evaluate the Safety and Efficacy of Pomalidomide Monotherapy in Subjects With Refractory or Relapsed Refractory Multiple Myeloma

Open-label, Multi-center, Single Arm Study For The Safety And Efficacy Of Pomalidomide Monotherapy For Subjects With Refractory Or Relapsed And Refractory Multiple Myeloma. A Companion Study For Clinical Trial CC-4047-MM003

Objective response defined as a best overall response of stringent complete response (SCR), complete response (CR), very good partial response (VGPR) or partial response (PR) based on Investigator Assessment.

SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein and urine M-protein level \<100 mg/24 hours; PR: ≥50% reduction of serum M-Protein and reduction in urinary M-protein by ≥90% or to \<200 mg/24 hours. A ≥50% decrease in the difference between involved and uninvolved FLC levels in place of the M-protein criteria or a ≥50% reduction in plasma cells in place of M-protein if baseline was ≥30%. If present at baseline a ≥50% reduction in size of soft tissue plasmacytomas.

Objective response defined as a best overall response of complete response (CR) or partial response (PR) based on the CR and requires all of the following:

* Absence of original monoclonal paraprotein in serum and urine by immunofixation maintained at least 42 days.
* \<5% plasma cell in bone marrow aspirate and on bone marrow biopsy, if performed.
* No increase in size or number of lytic bone lesions.
* Disappearance of soft tissue plasmacytomas.

PR requires all of the following:

* ≥50% reduction in level of serum monoclonal paraprotein, maintained at least 42 days.
* Reduction in 24-hour urinary light chain extraction by ≥90% or to \<200 mg, maintained at least 42 days.
* For patients with non-secretory myeloma, ≥50% reduction in plasma cells in bone marrow aspirate and on biopsy, if performed, for at least 42 days.

An adverse event is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A serious AE is any AE occurring at any dose that:

* Results in death;
* Is life-threatening;
* Requires or prolongs existing inpatient hospitalization;
* Results in persistent or significant disability/incapacity;
* Is a congenital anomaly/birth defect;
* Constitutes an important medical event.

The Investigator assessed the relationship of each AE to study drug and graded the severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0):

Grade 1 = Mild (no limitation in activity or intervention required); Grade 2 = Moderate (some limitation in activity; no/minimal medical intervention required);-Grade 3 = Severe (marked limitation in activity; medical intervention required, hospitalization possible); Grade 4 = Life-threatening; Grade 5 = Death

Progression-free survival was calculated as the time from randomization to disease progression as determined by the Investigator based on the International Myeloma Working Group Uniform Response criteria (IMWG), or death on study, whichever occurred earlier.

Progressive disease requires 1 of the following:

* Increase of ≥ 25% from nadir in:

  * Serum M-component (absolute increase ≥ 0.5 g/dl)
  * Urine M-component (absolute increase ≥ 200 mg/24 hours)
  * In patients without measurable serum and urine M-protein levels the difference between involved and uninvolved free light chain (FLC) levels (absolute increase \> 100 mg/dl)
  * Bone marrow plasma cell percentage (absolute % ≥ 10%)
* Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas.

Time to progression (TTP) was calculated as the time from randomization to the first documented progression confirmed by the investigator and based on the International Myeloma Working Group Uniform Response criteria (IMWG).

Progressive disease requires 1 of the following:

* Increase of ≥ 25% from nadir in:

  * Serum M-component (absolute increase ≥ 0.5 g/dl)
  * Urine M-component (absolute increase ≥ 200 mg/24 hours)
  * In patients without measurable serum and urine M-protein levels the difference between involved and uninvolved free light chain (FLC) levels (absolute increase \> 100 mg/dl)
  * Bone marrow plasma cell percentage (absolute % ≥ 10%)
* Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas.
* Development of hypercalcemia (corrected serum calcium \> 11.5 mg/dl) attributed solely to plasma cell proliferative disease.

Duration of Response (calculated for responders only) is defined as the time from the initial documented response (partial response or better) to confirmed disease progression by the investigator based on IMWG criteria.

Overall survival was calculated as the time from randomization to death from any cause. Overall survival was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented.

Time to Response was calculated as the time from enrollment to the initial response (PR or better) based on IMWG and assessed by the investigator.

Celgene

Oral pomalidomide 4 mg on Days 1-21 of each 28-day cycle until progressive disease (PD) or unacceptable toxicity

Age, Continuous

Sex: Female, Male

American Indian or Alaska Native

Asian

Black or African American

Native Hawaiian or Other Pacific Islanders

White

Other

Not Collected

Race

Hispanic or Latino

Not Hispanic or Latino

Ethnicity

Participants with Prior Anti-Myeloma (MM) Therapies

Stage I

Stage II

Stage III

Missing

Stages are:

Stage I: Hemoglobulin \> 10 g/dL; serum calcium normal on roentgenogram; normal bone structure or solitary bone plasmacytoma only; Low M-component production rates (IgG value \< 5 g/dL, IgA value \< 3 g/dL; Bence Jones protein \< 4 g/24h)

Stage II: Overall data as minimally abnormal for stage I, and no single value as abnormal as defined for stage III

Stage III: 1 or more of below:

Hemoglobin \< 8.5 g/dL; serum calcium \> 12 mg/dL; Advanced lytic bone lesions (scale 3); High-M-component production rates (IgG value \> 7 g/dL, IgA value \> 5 g/dL; Bence Jones protein \> 12 g/24h)

Durie-Salmon Multiple Myeloma Stage before Study Entry

Time From First Pathologic Diagnosis

The intent-to-treat (ITT) population was defined as all enrolled participants.

Anne McClain, Senior Manager, Clinical Trial Disclosure

Intent to Treat Population was defined as all enrolled participants.

Percentage of Participants With an Objective Response According to International Myeloma Working Group (IMWG) Uniform Response Criteria Based on Investigator Assessment

Oral pomalidomide 4 mg on Days 1-21 of 28-day cycle until progressive disease (PD) or unacceptable toxicity

pomalidomide: Oral pomalidomide 4 mg on Days 1-21 of each 28-day cycle until progressive disease (PD) or unacceptable toxicity

Intent to treat population includes all participants enrolled.

Percentage of Participants With Objective Response According to European Group for Blood and Marrow Transplantation (EBMT) Criteria Based on Investigator Assessment

Any adverse event

Grade 3-4 adverse event

AE related to pomalidomide

Grade 3-4 AE related to pomalidomide

Grade 5 AE

≥1 Serious AE (SAE)

≥1 SAE related to pomalidomide

≥1 SAE leading to stopping pomalidomide

≥AE leading to discontinuation of pomalidomide

≥1 study drug related AE leading to stopping POM

≥1 AE leading to reduction of pomalidomide

≥1 study drug related AE leading to reducing POM

≥1 AE leading to interruption of pomalidomide

≥ 1 study drug related interruption of POM

Safety population includes all participants who received at least one dose of study drug.

Number of Participants With Adverse Events and Type of Adverse Events

Intent to Treat included all participants enrolled.

Kaplan Meier Estimates for Progression Free Survival (PFS) by Investigator Based on IMWG

Intent to Treat includes all participants enrolled

Kaplan-Meier Estimate for Time to Progression (TTP) Based on Investigator Assessment Using IMWG Criteria

Oral pomalidomide 4 mg on Days 1-21 of 28-day cycle until progressive disease (PD) or unacceptable toxicity

pomalidomide: Oral pomalidomide 4 mg on Days 1-21 of 28-day cycle until progressive disease (PD) or unacceptable toxicity

Includes those who had a partial response or better.

Kaplan-Meier Estimate Duration of Response Based on Investigator Assessment Using IMWG Criteria

Intent to Treat population included all participants enrolled into the study

Kaplan-Meier Estimate for Overall Survival

Includes those who had at least a partial response or better; Intent to Treat

Time to Response Based on IMWG and Assessed by the Investigator

Overall Study

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Dexamethasone

Dexamethasone acetate

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Participants received 4 mg pomalidomide administered by mouth on Days 1 to 21 of each 28-day treatment cycle and 40 mg dexamethasone (or 20 mg for participants \> 75 years of age) administered by mouth once per day on Days 1, 8, 15, and 22 of each 28-day cycle until disease progression.

Participants received 40 mg dexamethasone (or 20 mg for participants \> 75 years of age) administered by mouth once per day on Days 1 to 4, 9 to 12, and 17 to 20 of each 28-day treatment cycle until disease progression.

4 mg pomalidomide capsules administered orally

40 mg dexamethasone (or 20 mg for participants \> 75 years of age) tablets administered orally

Lars Sternas, MD, PhD

The purpose of this study is to compare efficacy and safety of pomalidomide in combination with low-dose dexamethasone versus high-dose dexamethasone in subjects with refractory or relapsed and refractory multiple myeloma.

A Phase 3, Multicenter, Randomized, Open-Label Study to Compare the Efficacy and Safety of Pomalidomide in Combination With Low-Dose Dexamethasone Versus High-Dose Dexamethasone in Subjects With Refractory Multiple Myeloma or Relapsed and Refractory Multiple Myeloma and Companion Study

A Phase 3, Muticenter, Randomized, Open-label Study to Compare the Efficacy and Safety of Pomalidomide in Combination With Low-dose Dexamethasone Versus High-dose Dexamethasone in Subjects With Refractory or Relapsed and Refractory Multiple Myeloma

Progression-free survival was calculated as the time from randomization to disease progression as determined by the Independent Response Adjudication Committee based on the International Myeloma Working Group Uniform Response criteria (IMWG), or death on study, whichever occurred earlier. Progressive disease required 1 of the following: • Increase of ≥ 25% from nadir in: o Serum M-component (absolute increase ≥ 0.5 g/dl); o Urine M-component (absolute increase ≥ 200 mg/24 hours); o Bone marrow plasma cell percentage (absolute % ≥ 10%); • Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas; • Development of hypercalcemia (corrected serum calcium \> 11.5 mg/dl) attributed solely to plasma cell proliferative disease.

Progression-free survival was calculated as the time from randomization to disease progression as determined by the Independent Response Adjudication Committee based on the International Myeloma Working Group Uniform Response criteria (IMWG), or death on study, whichever occurred earlier. Progressive disease requires 1 of the following: • Increase of ≥ 25% from nadir in: o Serum M-component (absolute increase ≥ 0.5 g/dl); o Urine M-component (absolute increase ≥ 200 mg/24 hours); o Bone marrow plasma cell percentage (absolute % ≥ 10%); • Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas; • Development of hypercalcemia (corrected serum calcium \> 11.5 mg/dl) attributed solely to plasma cell proliferative disease.

An adverse event is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A serious AE is any AE occurring at any dose that: • Results in death; • Is life-threatening; • Requires or prolongs existing inpatient hospitalization; • Results in persistent or significant disability/incapacity; • Is a congenital anomaly/birth defect; • Constitutes an important medical event. The Investigator assessed the relationship of each AE to study drug and graded the severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0): Grade 1 = Mild (no limitation in activity or intervention required); Grade 2 = Moderate (some limitation in activity; no/minimal medical intervention required); Grade 3 = Severe (marked limitation in activity; medical intervention required, hospitalization possible); Grade 4 = Life-threatening; Grade 5 = Death.

Overall survival is calculated as the time from randomization to death from any cause. Overall survival was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented.

Objective response is defined as a best overall response of stringent complete response (SCR), complete response (CR), very good partial response (VGPR) or partial response (PR) based on the Independent Response Adjudication Committee: SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level \< 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to \< 200 mg/24 hours. In addition to the above, if present at baseline a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required.

Objective response defined as a best overall response of complete response (CR) or partial response (PR) based on the Independent Response Adjudication Committee: CR requires all of the following: - Absence of original monoclonal paraprotein in serum and urine by immunofixation maintained at least 42 days. - \<5% plasma cell in bone marrow aspirate and on bone marrow biopsy, if performed. - No increase in size or number of lytic bone lesions. - Disappearance of soft tissue plasmacytomas. PR requires all of the following: - ≥ 50% reduction in level of serum monoclonal paraprotein, maintained at least 42 days. - Reduction in 24-hour urinary light chain extraction by ≥ 90% or to \< 200 mg, maintained at least 42 days. - For patients with non-secretory myeloma, ≥ 50% reduction in plasma cells in bone marrow aspirate and on biopsy, if performed, for at least 42 days. - ≥ 50% reduction in the size of soft tissue plasmacytomas. - No increase in size or number of lytic bone lesions.

Time to progression (TTP) is calculated as the time from randomization to the first documented progression confirmed by a blinded, independent Response Adjudication Committee and based on the International Myeloma Working Group Uniform Response criteria (IMWG). Progressive disease requires 1 of the following: • Increase of ≥ 25% from nadir in: o Serum M-component (absolute increase ≥ 0.5 g/dl); o Urine M-component (absolute increase ≥ 200 mg/24 hours); o Bone marrow plasma cell percentage (absolute % ≥ 10%); • Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas; • Development of hypercalcemia (corrected serum calcium \> 11.5 mg/dl) attributed solely to plasma cell proliferative disease.

Time to response is calculated as the time from randomization to the initial documented response (partial response or better) based on IMWG criteria. SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level \< 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to \< 200 mg/24 hours. If present at baseline a ≥ 50% reduction in size of soft tissue plasmacytomas is also required.

Duration of response (calculated for responders only) is defined as time from the initial documented response (partial response or better) to confirmed disease progression, based on IMWG criteria assessed by the Independent Response Adjudication Committee.

Time to increased hemoglobin, defined as the time from randomization to at least one category improvement from Baseline in common terminology criteria for adverse events (CTCAE) grade for hemoglobin level. Hemoglobin categories are: 1) Normal; 2) CTCAE Grade 1: \< lower limit of normal (LLN) to 10.0 g/dL; 3) CTCAE Grade 2: \< 10.0 to \<8.0 g/dL. Participants with CTCAE Grade 3 anemia or worse at Baseline were excluded from the study.

Time to improvement in bone pain is defined as the time from randomization to at least one category improvement from Baseline in bone pain category. Bone pain was categorized (from best to worst) according to answers to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for patients with Multiple Myeloma Module (QLQ-MY20), Question 1, "Have you had bone aches or pain?": 1) Not at all, 2) A little, 3) Quite a bit, or 4) Very much.

Time to improvement in renal function is defined as the time from randomization to at least one category improvement from Baseline in renal function. Renal Function was categorized as (from best to worst): - Normal: creatinine clearance ≥80 mL/min; - Grade 1: creatinine clearance ≥60 to \<80 mL/min; - Grade 2 : creatinine clearance ≥45 to \< 60 mL/min. Participants with creatinine clearance \< 45 mL/min at baseline were excluded from the study.

Time to improvement in ECOG performance status defined as the time from randomization until at least a one category improvement from Baseline in ECOG performance status score. The categories of the ECOG Performance Status Scale are as follows: -0: Fully active, able to carry on all pre-disease performance without restriction; -1: Restricted in physically strenuous activity but ambulatory and able to carry our work of a light or sedentary nature, e.g., light housework, office work; -2: Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. Patients with a score of 3, 4 or 5 were excluded from participating in the study.

The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status/QOL scale is scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in QOL or functioning and positive values indicate improvement.

The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Physical Functioning Scale is scored between 0 and 100, with a high score indicating better functioning/support. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.

The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Emotional Functioning Scale is scored between 0 and 100, with a high score indicating better functioning/support. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.

The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate reduction in fatigue (i.e. improvement in symptom) and positive values indicate increases in fatigue (i.e. worsening of symptom).

The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Pain Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate reductions in pain (i.e. improvement in symptom) and positive values indicate increases in pain (i.e. worsening of symptom).

The European Organization for Research and Treatment of Cancer QoL Questionnaire for Patients with Multiple Myeloma (EORTC QLQ-MY20) is a 20-question tool used in clinical research to assess health-related quality of life in multiple myeloma patients. The QLQ-MY20 includes four domains (Disease Symptoms, Side-Effects of Treatment, Body Image and Future Perspective). The EORTC QLQ-MY20 Disease Symptoms Scale is scored between 0 and 100, with a high score reflecting a higher level of symptoms. Negative change from Baseline values indicate reduction (i.e. improvement) in symptoms and positive values indicate increase (i.e. worsening) of symptoms.

The European Organization for Research and Treatment of Cancer QoL Questionnaire for Patients with Multiple Myeloma (EORTC QLQ-MY20) is a 20-question tool used in clinical research to assess health-related quality of life in multiple myeloma patients. The QLQ-MY20 includes four domains (Disease Symptoms, Side-Effects of Treatment, Body Image and Future Perspective). The EORTC QLQ-MY20 Side Effects Scale is scored between 0 and 100, with a high score reflecting a higher level of symptoms. Negative change from Baseline values indicate reduction in side effects (i.e.improvement in symptom) and positive values indicate increase in side effects (i.e. worsening of symptom).

EQ-5D is a self-administered questionnaire that assesses health-related quality of life (QOL). The EQ-5D descriptive health profile comprises five dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 3 levels of response: No problem (1), some problems (2), and extreme problems (3). A unique EQ-5D health state is defined by combining one level from each of the five dimensions into a single utility index score. EQ-5D index values range from -0.59 to 1.00 where an EQ-5D score of 1.00 equals "perfect health", a score of 0 equals "death" and a score of -0.59 equals worst imaginable health state. A positive change from Baseline score indicates improvement in health status. A negative change from Baseline score indicates worsening in health status. Negative scores represent the possible though unlikely situation that a patient's QOL is worse than death, i.e. they would rather be dead than living with that QOL

Time to worsening in quality of life domains was calculated as the time from Baseline to the first worsened minimally important difference (MID), defined as the smallest change in a QOL score considered important to patients that would lead the patient or clinician to consider a change in therapy. MID thresholds were calculated in Standard Error of Measurement (SEM) units using the Baseline QOL data. Based on the MID, participants were classified as worsened according to the following: For the EORTC QLQ-C30 global health status and functional scales and the EQ-5D health utility score, participants were classified as worsened if their change from Baseline score was less than -1 SEM. For the EORTC QLQ-C30 symptom scores (fatigue and pain) and EORTC QLQ-MY20 disease symptoms and side effects scales, participants were classified as worsened if their change from Baseline score was greater than 1 SEM. See previous outcome measures for definitions of each scale.

Participants received 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle and 40 mg dexamethasone (participants \> 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression.

Pomalidomide Plus Low-Dose Dexamethasone

Participants received 40 mg dexamethasone (participants \> 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle until disease progression, or until cross-over to pomalidomide. Data are up to the time of cross-over.

High-Dose Dexamethasone

Participants initially randomized to high-dose dexamethasone (HD-Dex) crossed over to receive 4 mg pomalidomide administered by mouth on Days 1-21 of each 28-day treatment cycle, with or without low-dose dexamethasone (40 mg for participants ≤ 75 years or 20 mg for participants \> 75 years of age, administered orally once per day on Days 1, 8, 15, and 22 of each 28-day cycle) at the discretion of the investigator. Data include AEs that occurred after cross-over to pomalidomide.

HD-Dex / Pomalidomide

Participants received 40 mg dexamethasone (participants \> 75 years of age received 20 mg dexamethasone) administered by mouth once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle until disease progression.

Total

Age, Customized

Ethnicity (NIH/OMB)

Race/Ethnicity, Customized

Time from First Pathologic Diagnosis

Disease Population Group 1 is defined as refractory patients who have progressed on or within 60 days of both lenalidomide and bortezomib based treatments. Disease Population Group 2 is defined as relapsed and refractory patients who achieved at least a partial response (PR) and progressed within 6 months after stopping treatment with lenalidomide and/or bortezomib. Disease Population Group 3 is defined as refractory/intolerant patients who developed intolerance/toxicity after a minimum of 2 cycles of bortezomib.

Stratification Factor 2: Disease Population

Stratification Factor 3: Number of Prior Anti-MM Therapies

The International Staging System divides myeloma into 3 stages based only on the serum beta-2 microglobulin and serum albumin levels. Stage I: Serum beta-2 microglobulin is less than 3.5 (mg/L) and the albumin level is above 3.5 (g/L); Stage II: Neither stage I or III, meaning that either: ◾ The beta-2 microglobulin level is between 3.5 and 5.5 (with any albumin level), OR ◾ The albumin is below 3.5 while the beta-2 microglobulin is less than 3.5 Stage III: Serum beta-2 microglobulin is greater than 5.5.

Multiple Myeloma Stage before Study Entry

Intent-to-treat population (all participants who were randomized, regardless of whether they received study treatment or not)

Associate Director, Clinical Trials Disclosure

Progression-free Survival (PFS) - Primary Analysis

Progression-free Survival (PFS) With a Later Cut-off Date

Grade 3-4 adverse events

AE related to dexamethasone

AE related to either study drug

Grade 3-4 AE related to dexamethasone

Grade 3-4 AE related to either study drug

Grade 5 adverse events

Serious adverse events (SAEs)

SAE related to pomalidomide

SAE related to dexamethasone

SAE related to either study drug

SAE leading to discontinuation of pomalidomide

SAE leading to discontinuation of dexamethasone

SAE leading to discontinuation of either study dru

AE leading to discontinuation of pomalidomide

AE leading to discontinuation of dexamethasone

AE leading to discontinuation of either study drug

Safety population (all randomized participants who received at least one dose of study drug (either pomalidomide or dexamethasone)).

Number of Participants With Adverse Events (AEs)

Overall Survival - Primary Analysis

Overall Survival With a Later Cut-off Date

Overall Survival Based on the Final Dataset

Percentage of Participants With an Objective Response According to International Myeloma Working Group (IMWG) Uniform Response Criteria

Percentage of Participants With Objective Response According to European Group for Blood and Marrow Transplantation (EBMT) Criteria

Time to Progression

Time to Response

Duration of Response

Intent-to-treat population with improvement in hemoglobin during the study

Time to the First Hemoglobin Improvement

Intent-to-treat population with improvement in bone pain

Time to Improvement in Bone Pain

Intent-to-treat population with improvement in renal function

Time to Improvement in Renal Function

Intent-to-treat population with improvement in ECOG performance status during the study

Time to Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status

Cycle 2, Day 1

Cycle 3, Day 1

Cycle 4, Day 1

Cycle 5 Day 1

Cycle 6, Day 1

The Patient Reported Outcomes (PRO) study population includes any intent-to-treat study participants with 1 active treatment and 1 PRO measurement item completed. Only participants with available data at Baseline and each time point are included.

Change From Baseline in the European Organization for Research and Treatment of Cancer Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Domain

PRO population with available data at Baseline and each time point.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study to Evaluate the Safety and Efficacy of Pomalidomide Monotherapy in Subjects With Refractory or Relapsed Refractory Multiple Myeloma	NCT01324947	Multiple Myelom...	pomalidomide	18 Years -	Celgene
A Phase 3, Multicenter, Randomized, Open-Label Study to Compare the Efficacy and Safety of Pomalidomide in Combination With Low-Dose Dexamethasone Versus High-Dose Dexamethasone in Subjects With Refractory Multiple Myeloma or Relapsed and Refractory Multiple Myeloma and Companion Study	NCT01311687	Multiple Myelom...	pomalidomide Dexamethasone	18 Years -	Celgene
Study to Determine the Maximum Tolerated Dose for the Combination of Pomalidomide, Bortezomib and Low-Dose Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma	NCT01497093	Multiple Myelom...	Pomalidomide Bortezomib Dexamethasone	18 Years -	Celgene

Spots Global Cancer Trial Database for resistant multiple myeloma