Study of Single Agent Belantamab Mafodotin Versus Pomalidomide Plus Low-dose Dexamethasone (Pom/Dex) in Participants With Relapsed/Refractory Multiple Myeloma (RRMM) (DREAMM-3)
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| ClinicalTrials.gov Identifier: NCT04162210 |
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Recruitment Status :
Active, not recruiting
First Posted : November 14, 2019
Last Update Posted : September 30, 2022
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Sponsor:
GlaxoSmithKline
Information provided by (Responsible Party):
GlaxoSmithKline
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Brief Summary:
This open-label, randomized study for evaluating the efficacy and safety of single agent belantamab mafodotin when compared to pom/dex in participants with RRMM. Participants will be randomized in a 2:1 ratio to receive either single agent belantamab mafodotin or pom/dex. Belantamab mafodotin will be administered on Day 1 (D1) at every 3 weeks (Q3W) schedule. Pomalidomide will be administered daily on Days 1 to 21 of each 28-day cycle, with dexamethasone administered once weekly (Days 1, 8, 15, and 22). Participants in both arms will be treated until disease progression, death, unacceptable toxicity, withdrawal of consent, and lost to follow-up or end of study, whichever comes first.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Multiple Myeloma | Drug: Belantamab mafodotin Drug: Pom/dex (Pomalidomide plus low dose Dexamethasone) | Phase 3 |
Expanded Access : An investigational treatment associated with this study has been approved for sale to the public. More info ...
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 338 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | This is an open-label, randomized and multi-center study |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase III, Open-Label, Randomized Study to Evaluate the Efficacy and Safety of Single Agent Belantamab Mafodotin Compared to Pomalidomide Plus Lowdose Dexamethasone (Pom/Dex) in Participants With Relapsed/Refractory Multiple Myeloma (RRMM) (DREAMM 3) |
| Actual Study Start Date : | April 2, 2020 |
| Actual Primary Completion Date : | September 12, 2022 |
| Estimated Study Completion Date : | March 28, 2025 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Multiple myeloma
MedlinePlus related topics:
Multiple Myeloma
| Arm | Intervention/treatment |
|---|---|
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Experimental: Participants receiving Belantamab mafodotin
Participants will receive belantamab mafodotin single agent dose on Day 1 of Q3W
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Drug: Belantamab mafodotin
Belantamab mafodotin will be administered. |
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Active Comparator: Participants receiving pom/dex
Participants will receive pomalidomide daily on Days 1 to 21 of each 28-day cycle, with dexamethasone once weekly on Days 1, 8, 15 and 22.
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Drug: Pom/dex (Pomalidomide plus low dose Dexamethasone)
Pomalidomide and Dexamethasone will be administered. |
Primary Outcome Measures :
- Progression-free survival (PFS) [ Time Frame: Up to 25 months ]PFS is defined as the time from the date of randomization until the earliest date of documented disease progression (according to International Myeloma Working Group [IMWG] Response Criteria) or death due to any cause.
Secondary Outcome Measures :
- Overall survival (OS) [ Time Frame: 60 months ]OS is defined as the time from randomization until death due to any cause.
- Overall response rate (ORR) [ Time Frame: Up to 55 months ]ORR is defined as the percentage of participants with a confirmed partial response (PR) or better per IMWG.
- Clinical benefit rate (CBR) [ Time Frame: Up to 55 months ]CBR is defined as the percentage of participants with a confirmed minimal response (MR) or better per IMWG.
- Duration of response (DoR) [ Time Frame: Up to 55 months ]DoR is defined as the time from first documented evidence of PR or better until progressive disease (PD) per IMWG or death due to PD among participants who achieve confirmed PR or better.
- Time to response (TTR) [ Time Frame: Up to 55 months ]TTR is defined as the time between the date of randomization and the first documented evidence of response (PR or better) among participants who achieve confirmed PR or better.
- Time to progression (TTP) [ Time Frame: Up to 55 months ]TTP is defined as the time from the date of randomization until the earliest date of documented PD (per IMWG Response Criteria) or death due to PD.
- Number of participants with adverse events (AEs) [ Time Frame: Up to 55 months ]An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment.
- Change from Baseline in hematology parameters: absolute white blood cell count (WBC), basophils,eosinophils, lymphocytes, monocytes, platelet count, and neutrophils (Giga cells per liter) [ Time Frame: Baseline and up to 55 months ]Blood samples will be collected for the analysis of hematology parameters.
- Change from Baseline in hematology parameters: Red Blood Cell (RBC) count and reticulocyte count (Trillion cells per liter) [ Time Frame: Baseline and up to 55 months ]Blood samples will be collected for the analysis of hematology parameters.
- Change from Baseline in hematology parameters: Mean Corpuscular Hemoglobin concentration (MCHC) and hemoglobin (Grams per Liter) [ Time Frame: Baseline and up to 55 months ]Blood samples will be collected for the analysis of hematology parameters.
- Change from Baseline in hematology parameters: Hematocrit (Proportion of red blood cells in blood) [ Time Frame: Baseline and up to 55 months ]Blood samples will be collected for the analysis of hematology parameters.
- Change from Baseline in hematology parameters: Mean Corpuscular Volume (MCV) [Femtoliter] [ Time Frame: Baseline and up to 55 months ]Blood samples will be collected for the analysis of hematology parameters.
- Change from Baseline in hematology parameters: Mean Corpuscular Hemoglobin (MCH) [Picograms] [ Time Frame: Baseline and up to 55 months ]Blood samples will be collected for the analysis of hematology parameters.
- Change from Baseline in clinical chemistry parameters: Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine kinase (CK), Gamma Glutamyl Transferase (GGT), and lactate dehydrogenase (LDH) [ Time Frame: Baseline and up to 55 months ]Blood samples will be collected for the analysis of clinical chemistry parameters like ALT, AST, ALP, CK, GGT, and LDH [International units per Liter].
- Change from Baseline in clinical chemistry parameters: Calcium, chloride, glucose, potassium, sodium, magnesium, blood urea nitrogen (BUN), and phosphorous (Millimoles per Liter) [ Time Frame: Baseline and up to 55 months ]Blood samples will be collected for the analysis of clinical chemistry parameters.
- Change from Baseline in clinical chemistry parameters: Creatinine, direct bilirubin, total bilirubin, uric acid (Micromoles per liter) [ Time Frame: Baseline and up to 55 months ]Blood samples will be collected for the analysis of clinical chemistry parameters.
- Change from Baseline in clinical chemistry parameters: Albumin and total protein (Grams per Liter) [ Time Frame: Baseline and up to 55 months ]Blood samples will be collected for the analysis of clinical chemistry parameters.
- Change from Baseline in Urinalysis Parameter: Specific Gravity (Ratio) [ Time Frame: Baseline and up to 55 months ]Urine samples will be collected for the assessment of specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity.
- Change from Baseline in Urinalysis Parameters- Urine potential of hydrogen (pH) (Points on a scale) [ Time Frame: Baseline and up to 55 months ]Urine samples will be collected for the assessment of Urinary pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0).
- Change from Baseline in urinalysis parameter: Glucose (Millimole per liter) [ Time Frame: Baseline and up to 55 months ]Urine samples will be collected for the assessment of urinary glucose.
- Change from Baseline in urinalysis parameter: Protein (Grams per liter) [ Time Frame: Baseline and up to 55 months ]Urine samples will be collected for the assessment of urinary protein.
- Change from Baseline in urinalysis parameter: Ketones (Millimoles per liter) [ Time Frame: Baseline and up to 55 months ]Urine samples will be collected for the assessment of urinary ketones.
- Change from Baseline in urinalysis parameter: blood (10^9 cells per liter) [ Time Frame: Baseline and up to 55 months ]Urine samples will be collected for the assessment of urinary blood.
- Change from Baseline in urinalysis parameter: creatinine/albumin ratio (ratio) [ Time Frame: Baseline and up to 55 months ]Urine samples will be collected for the assessment of urinary creatinine/albumin ratio.
- Number of participants with abnormal ocular findings [ Time Frame: Up to 55 months ]Participants will be assessed for any abnormal ocular findings.
- Plasma concentrations of belantamab mafodotin [ Time Frame: Up to 55 months ]Blood samples will be collected for the analysis.
- Plasma concentrations of total monoclonal antibody (mAb) [ Time Frame: Up to 55 months ]Blood samples will be collected for the analysis.
- Plasma concentrations of cys-mc Microtubular inhibitor monomethyl auristatin-F (MMAF) [ Time Frame: Up to 55 months ]Blood samples will be collected for the analysis.
- Number of participants with Anti-drug antibody (ADAs) against belantamab mafodotin [ Time Frame: Up to 55 months ]Blood samples will be collected for the analysis.
- Titer of ADAs against belantamab mafodotin [ Time Frame: Up to 55 months ]Blood samples will be collected for the analysis.
- Number of participants with symptomatic adverse effects measured by Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) [ Time Frame: Up to 55 months ]PRO-CTCAE is a patient-reported outcome measure developed to evaluate symptomatic toxicity in participants on cancer clinical trials. The PRO-CTCAE includes an item library of 124 items representing 78 symptomatic toxicities drawn from the CTCAE.
- Number of participants with symptomatic adverse effects measured by Ocular Surface Disease Index (OSDI) [ Time Frame: Up to 55 months ]OSDI is a 12-item questionnaire designed to assesses both the frequency of dry eye symptoms and their impact on vision-related functioning. It is graded on a scale of 0-4, with 0 indicating none of the time, 1 for some of the time, 2 for half of the time, 3 for most of the time and 4 indicating all the time. A higher score represents greater symptoms severity.
- European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-item Core module (EORTC QLQC30) score [ Time Frame: Up to 55 months ]The EORTC QLQ-C30 is a 30-item questionnaire containing both single- and multi-item measures. These include five functional scales (Physical, Role, Cognitive, Emotional, and Social Functioning), three symptom scales (Fatigue, Pain, and Nausea/Vomiting), a Global Health Status/quality of life (QoL) scale, and six single items (Constipation, Diarrhea, Insomnia, Dyspnea, Appetite Loss, and Financial Difficulties). Scores for each scale and single-item measure are averaged and transformed linearly to a score ranging from 0-100.
- European Organization for Research and Treatment of Cancer IL52 (EORTC IL52) score [ Time Frame: Up to 55 months ]The EORTC Quality of Life Questionnaire 20-item Multiple Myeloma module (QLQMY20) is a supplement to the QLQ-C30 instrument used in participants with multiple myeloma. For the EORTC IL52, disease symptoms domain of the QLQ-MY20 will be used for bone aches or pain, back pain, hip pain, arm or shoulder pain, chest pain, and pain increasing with activity. The individual component scores in the disease symptom domain are averaged and transformed linearly to a score ranging from 0 to100. A high score for disease symptoms represents a high level of symptomatology or problems. A high score represents a high/healthy level of functioning.
- EORTC Quality of Life Questionnaire 20-item Multiple Myeloma module (QLQMY20) Score [ Time Frame: Up to 55 months ]The EORTC QLQMY20 is a supplement to the QLQ-C30 instrument used in participants with multiple myeloma. It includes four scales (Disease Symptoms, Body Image, Future Perspective, and Side Effects). The domain scores are averaged and transformed linearly to a score ranging from 0 to 100. A high score represents a high level of symptomatology or problems.
- Rate of Minimal Residual Disease (MRD) [ Time Frame: Up to 55 months ]MRD negativity rate, defined as; the percentage of participants who are MRD negative by Next generation sequencing (NGS) method.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Capable of giving signed informed consent.
- Participants must be 18 or older, at the time of signing the informed consent. In Republic of Korea, participants must be over 19 years of age inclusive, at the time of signing informed consent.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
- Histologically or cytologically confirmed diagnosis of Multiple myeloma (MM) as defined according to IMWG, and : Has undergone autologous stem cell transplant (SCT), or is considered transplant ineligible; Has received at least 2 prior lines of anti-myeloma treatments, including at least 2 consecutive cycles of both lenalidomide and a proteasome inhibitor (given separately or in combination), and must have documented disease progression on, or within 60 days of, completion of the last treatment or must be non-responsive while on last treatment, where non-responsive is defined as not achieving at least Minimal Response (MR) after 2 complete treatment cycles. In such cases lack of achieving of at least MR must be determined no earlier than at least 4 weeks after the last treatment.
- Has measurable disease with at least one of the following: Serum M-protein >=0.5 gram per deciliter (g/dL) (>=5 gram per Liter); Urine M-protein >=200 mg/24 hours; Serum free light chain (FLC) assay: Involved FLC level >=10 milligram per deciliter (mg/dL) (>=100 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65).
- Participants with a history of autologous SCT are eligible for study participation provided the following eligibility criteria are met: Transplant was >100 days prior to initiating study treatment; No active infection(s).
- Adequate organ system functions as defined: Absolute neutrophil count (ANC) >=1.0*10^9/L; Hemoglobin >= 8.0 g/dL; Platelets >= 50x10^9/L; Total bilirubin <=1.5* Upper limit of normal (ULN) (isolated bilirubin >1.5*ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent); ALT <=2.5*ULN; Estimated glomerular filtration rate (eGFR) >=30 milliliter per minute per 1.73 square meter (mL/min/1.73 m^2); Spot urine (albumin/creatinine ratios) <=500 milligram per gram (mg/g) (56 milligram per millimoles [mg/mmol]).
- Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Male participants are eligible to participate if they agree to the following during the intervention period and until 6 months after the last dose of study intervention to allow for clearance of any altered sperm: Refrain from donating sperm PLUS, either: Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR Must agree to use contraception/barrier as detailed below depending on whether they are randomised to Arm 1 (belantamab mafodotin) or Arm 2 (pom/dex), even if they have undergone a successful vasectomy: Agree to use a male condom throughout study treatment including the 6 month follow-up period even if they have undergone a successful vasectomy and a female partner to use an additional highly effective contraceptive method with a failure rate of <1 percent per year when having sexual intercourse with a pregnant woman or a woman of childbearing potential who is not currently pregnant. Four weeks for male participants on Treatment Arm 2 (pom/dex).
- A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP) OR Is a WOCBP and agrees to abide by the following: Arm 1 (belantamab mafodotin): Use a contraceptive method that is highly effective (with a failure rate of <1 percent per year) which includes abstinence, preferably with low user dependency during the intervention period and for 4 months after the last dose of study treatment. Arm 2 (pom/dex): Due to pomalidomide being a thalidomide analogue with risk for embryofetal toxicity and prescribed under a pregnancy prevention/controlled distribution program, WOCBP participants will be eligible if they commit either to abstain continuously from heterosexual sexual intercourse or to use two methods of reliable birth control (one method that is highly effective), beginning 4 weeks prior to initiating treatment with pomalidomide, during therapy, during dose interruptions and continuing for at least 4 weeks following discontinuation of pomalidomide treatment. Two negative pregnancy tests must be obtained prior to initiating therapy. The first test should be performed within 10-14 days and the second test within 24 hours prior to prescribing pomalidomide therapy. And agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should confirm the effectiveness of the contraceptive method(s) ahead of the first dose of study intervention.
- All prior treatment-related toxicities (defined by National Cancer Institute- Common Toxicity Criteria for Adverse Events [NCI-CTCAE], version 5.0, 2017) must be <=Grade 1 at the time of enrollment, except for alopecia and Grade 2 peripheral neuropathy.
Exclusion Criteria:
- Symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes); active plasma cell leukemia at the time of screening.
- Systemic anti-myeloma therapy or use of an investigational drug within <14 days or 5 half-lives, whichever is shorter, before the first dose of study intervention.
- Prior treatment with an anti-MM monoclonal antibody within 30 days prior to receiving the first dose of study intervention.
- Prior B cell maturation antigen (BCMA)-targeted therapy or prior pomalidomide treatment.
- Plasmapheresis within 7 days prior to the first dose of study intervention.
- Prior allogeneic stem cell transplant. (Participants who have undergone syngeneic transplant will be allowed only if no history of, or currently active, Graft-Versus-Host Disease [GvHD]).
- Any major surgery within the last 4 weeks.
- Presence of active renal condition (infection, requirement for dialysis or any other condition that could affect participant's safety). Participants with isolated proteinuria resulting from MM are eligible, provided they fulfil criteria as described in inclusion criteria.
- Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions (including lab abnormalities) that could interfere with participant's safety, obtaining informed consent, or compliance with study procedures.
- History of (non-infectious) pneumonitis that required steroids, or current pneumonitis.
- Evidence of active mucosal or internal bleeding.
- Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. (Stable chronic liver disease [including Gilbert's syndrome or asymptomatic gallstones] or hepatobiliary involvement of malignancy is acceptable if participant otherwise meets entry criteria)
- Participants with previous or concurrent malignancies other than multiple myeloma are excluded, unless the second malignancy has been considered medically stable for at least 2 years. The participant must not be receiving active therapy, other than hormonal therapy for this disease. (Participants with curatively treated non-melanoma skin cancer are allowed without a 2-year restriction).
- Evidence of cardiovascular risk including any of the following: Evidence of current clinically significant uncontrolled arrhythmias including clinically significant electrocardiogram (ECG) abnormalities including 2nd degree (Mobitz Type II) or 3rd degree atrioventricular block; History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 3 months of Screening; Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system; Uncontrolled hypertension.
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to belantamab mafodotin, pomalidomide, dexamethasone or any of the components of the study intervention.
- Pregnant or lactating female.
- Active infection requiring treatment.
- Known human immunodeficiency virus (HIV), unless the participant can meet all of the following criteria: Established anti-retroviral therapy (ART) for at least 4 weeks and HIV viral load <400 copies/mL; CD4+ T-cell (CD4+) counts ≥350 cells/uL; No history of AIDS-defining opportunistic infections within the last 12 months.(Consideration must be given to ART and prophylactic antimicrobials that may have a drug-drug interaction and/or overlapping toxicities with belantamab mafodotin or other combination products as relevant)
- Participants with Hepatitis B will be excluded unless the following criteria can be met: If the participant is hepatitis B core antibody (HbcAb) positive or hepatitis B surface antigen (HbsAg) negative, then hepatitis B virus (HBV) deoxyribonucleic acid (DNA) should be undectectable at the time of screening; If HbsAg+ at screening or <=3 months prior to first dose of study treatment, then HBV DNA should be undetectable, highly effective antiviral treatment should be started ≥4 weeks prior to first dose of study treatment, exclusion of participants with cirrhosis and participants in Japan must test hepatitis B e antigen (HBeAg) and hepatitis B e antibody (HBeAb ).
- Positive hepatitis C antibody test result or positive hepatitis C Ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment unless the participant can meet the following criteria: Hepatitis C RNA test negative at Screening and successful anti-viral treatment (usually 8 weeks duration) is required, followed by a negative HCV RNA test after a washout period of at least 4 weeks (Hepatitis RNA is optional and participants with negative Hepatitis C antibody test are not required to also undergo Hepatitis C RNA testing).
- Participants unable to tolerate thromboembolic prophylaxis.
- Current corneal epithelial disease except for mild punctate keratopathy.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04162210
Locations
Show 164 study locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
| Study Director: | GSK Clinical Trials | GlaxoSmithKline |
| Responsible Party: | GlaxoSmithKline |
| ClinicalTrials.gov Identifier: | NCT04162210 |
| Other Study ID Numbers: |
207495 2018-004252-38 ( EudraCT Number ) |
| First Posted: | November 14, 2019 Key Record Dates |
| Last Update Posted: | September 30, 2022 |
| Last Verified: | September 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | IPD for this study will be made available via the Clinical Study Data Request site. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (ICF) Clinical Study Report (CSR) |
| Time Frame: | IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints, and safety data of the study. |
| Access Criteria: | Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months. |
| URL: | http://clinicalstudydatarequest.com |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by GlaxoSmithKline:
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Belantamab mafodotin Pomalidomide Dexamethasone Relapsed/Refractory Multiple Myeloma Driving Excellence in Approaches to Multiple Myeloma 3 (DREAMM 3) |
Additional relevant MeSH terms:
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Multiple Myeloma Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Immunoproliferative Disorders Immune System Diseases Dexamethasone |
Pomalidomide Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal Antineoplastic Agents Immunologic Factors Angiogenesis Inhibitors Angiogenesis Modulating Agents |