Melphalan and Dexamethasone With or Without Bortezomib in Treating Patients With Previously Untreated Systemic Light-Chain Amyloidosis

Primary Systemic Amyloidosis Clinical Trial

Official title:

A Randomized Phase III Trial of Melphalan and Dexamethasone (MDex) Versus Bortezomib, Melphalan and Dexamethasone (BMDex) for Untreated Patients With Systemic Light-Chain (AL) Amyloidosis Ineligible for Autologous Stem-Cell Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01078454
• Other study ID #: NCI-2011-02010
• Secondary ID: NCI-2011-02010E4
• Status: Completed
• Phase: Phase 3
• Start date: November 2010
• Est. completion date: November 27, 2012

Study information

• Verified date: January 2022
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase III trial is studying melphalan and dexamethasone to see how well they work with or without bortezomib in treating patients with previously untreated systemic amyloidosis. Drugs used in chemotherapy, such as melphalan and dexamethasone, work in different ways to stop the growth of plasma cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of plasma cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving melphalan together with dexamethasone is more effective with or without bortezomib in treating systemic amyloidosis.

Description:

PRIMARY OBJECTIVES:

I. To compare hematologic overall response (partial response [PR], very good PR, amyloid complete hematologic response [ACR], and stringent complete response [sCR]) after 3 courses of therapy in patients with previously untreated systemic light-chain amyloidosis treated with melphalan and dexamethasone with vs without bortezomib.

SECONDARY OBJECTIVES:

I. To evaluate the ACR rate after 3 courses of therapy and at completion of therapy.

II. To evaluate organ response rates after 3 courses of therapy and at 6, 9, and 12 months.

III. To evaluate treatment-related mortality.

IV. To evaluate toxicity.

V. To evaluate progression-free and overall survival.

VI. To evaluate PR or better at completion of therapy.

VII. To evaluate time to hematologic and organ response.

VIII. To evaluate the duration of hematologic and organ response.

IX. To assess quality of life (QOL) at baseline, at 3, 6, and 9 months during the therapy, at completion of therapy, and 3 and 6 months after therapy.

TERTIARY OBJECTIVES:

I. To determine the prognostic impact of t(11;14) translocation and cyclin D1 overexpression on response and overall survival.

II. (Correlative) To compare sCR rates and to determine the impact of sCR on the outcomes.

III. (Correlative) To perform a descriptive analysis of amyloid typing and proteomic composition of amyloid tissues.

OUTLINE: This is a multicenter study. Patients are stratified according to amyloid cardiac stage (stage I/II vs. better risk stage III) and are randomized to 1 of 2 treatment arms.

ARM A (Mel-Dex): Patients receive melphalan 0.22 mg/kg orally (PO) and dexamethasone 40 mg PO on days 1-4 every 4 weeks. Treatment repeats every 4 weeks for up to 9 courses in the absence of disease progression or unacceptable toxicity.

ARM B (B-Mel-Dex): Patients receive melphalan 0.22 mg/kg PO and dexamethasone 40 mg PO on days 1-4 and bortezomib 1.3 mg/m2 intravenously (IV) on days 1, 4, 8, and 11 every 4 weeks. Treatment repeats every 4 weeks for 2 cycles. Patients then receive melphalan PO and dexamethasone PO on days 1-4 and bortezomib IV on days 1, 8, 15, and 22 every 5 weeks. Treatment repeats every 5 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Blood, urine, bone marrow, and fat samples may be collected periodically for laboratory analysis. Health-related quality of life is assessed periodically before, during, and after therapy. After completion of study treatment, patients are followed up periodically for 5 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: November 27, 2012
• Est. primary completion date: November 12, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed diagnosis of systemic light-chain amyloidosis

• Histologic diagnosis of disease must be confirmed by pathology (positive Congo red stain with green birefringence on polarized light microscopy)

• Genetic testing must be negative for transthyretin mutations associated with hereditary amyloidosis (required in patients who are African-American or who present with peripheral neuropathy as the dominant organ involvement)

• Measurable disease, defined by >= 1 of the following:

• Serum M-protein >= 1 g/dL by serum protein electrophoresis (SPEP)

• Difference between involved and uninvolved free light chain be >4.0mg/dL provided the kappa to lambda free light chain (FLC) ratio is abnormal

• Symptomatic organ involvement* (heart, kidney, liver/gastrointestinal tract, peripheral nervous system, or soft tissue), defined as any of the following:

• NOTE: *Carpal tunnel syndrome skin purpura or the presence of vascular amyloid on a bone marrow biopsy alone are not sufficient to meet criteria for "symptomatic organ involvement"

• Renal involvement is defined as proteinuria (predominantly albumin) > 0.5 g/day by 24-hour urine collection

• Cardiac involvement is defined as the presence of a mean left ventricular wall thickness of > 12 mm by echocardiogram in the absence of a history of hypertension or valvular heart disease or in the presence of unexplained low voltage (< 0.5 mV) by electrocardiogram

• Hepatic involvement is defined as hepatomegaly or an alkaline phosphatase > 1.5 times upper limit of normal (ULN)

• Peripheral nerve involvement is defined by clinical history or abnormal sensory and/or motor findings on neurologic exam

• Gastrointestinal (GI) involvement is defined as gross GI bleeding or diarrhea (at least 4 stools per day over baseline); a positive GI biopsy is not sufficient to document clinical involvement

• Autonomic nerve involvement is defined as orthostasis, symptoms of nausea or dysgeusia, gastric atony by gastric emptying scan, diarrhea, or constipation

• Soft tissue and lymphatic involvement may be ascertained based on classic physical exam findings (macroglossia, shoulder pad sign, raccoon eyes, carpal tunnel syndrome, synovial enlargement, firm enlarged lymph nodes) or biopsy

• Ineligible for autologous stem cell transplantation with melphalan 200 mg/m^2 or refuses to undergo transplantation

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Amyloid cardiac biomarker stage I or II disease

• The amyloid cardiac staging system is based on NT-proBNP and troponin-T levels. If troponin T (cTnT) is not available at local institution then troponin I (cTnI) may be used. Thresholds for cTnT, cTnI, and NT-proBNP are < 0.035 ug/L, < 0.1 ug/L, and < 332 ng/L, respectively. Stage I patients have both troponin-T (or I) and NT-proBNP below the threshold. Stage II patients have either troponin-T (I) or NT-proBNP above the threshold. Stage III patients have troponin-T (or I) and simultaneous NT-proBNP above the threshold. Stage III patients are further classified as "better risk" if NT-proBNP is over 332 ng/L but less than 6000 ng/L

• Negative pregnancy test

• Fertile patients must use effective contraception

• The absence of supine systolic blood pressure < 100 mmHg and difficult to manage symptomatic orthostatic hypotension

• Absolute neutrophil count (ANC) > 1,500/mm^3

• Platelet count > 140,000/mm^3

• Hemoglobin > 10 g/dL

• Total bilirubin < 2.5 mg/dL

• Alkaline phosphatase < 5 times upper limit of normal (ULN)

• Aspartate aminotransferase (AST) < 3 times ULN

• Creatinine clearance > 30 mL/min

• Bone marrow plasma cells < 30%

• Human immunodeficiency virus (HIV)-positivity allowed provided the following criteria are met:

• No history of acquired immunodeficiency syndrome (AIDS)-defining events including history of CD4 cell count < 200/mm^3

• Current CD4 cell count >= 350/mm^3

• Not receiving zidovudine or stavudine

• No secondary amyloidosis

• More than 3 weeks since radiotherapy

• Enrollment of subjects who require radiotherapy (which must be localized in field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy

• More than 14 days since prior and no concurrent participation in clinical trials with other investigational agents not included in this trial

Exclusion Criteria:

• Pregnant or nursing

• Clinically overt myeloma (hypercalcemia or lytic bone lesions)

• Prior chemotherapy or radiotherapy for the treatment of myeloma or systemic light-chain amyloidosis

• History of sustained ventricular tachycardias

• Cardiac syncope

• Uncompensated New York Heart Association (NYHA) class III or IV congestive heart failure

• Uncontrolled infection

• Active malignancy within the past 5 years except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or adequately treated stage I cancer currently in complete remission

• Serious medical or psychiatric illness likely to interfere with study participation, including recent myocardial infarction (within the past 6 months) or poorly controlled diabetes mellitus

• Hypersensitivity to bortezomib, boron, or mannitol

• Grade 2 or higher peripheral neuropathy

Related Conditions & MeSH terms

• Amyloidosis
• Immunoglobulin Light-chain Amyloidosis
• Light Chain Deposition Disease
• Primary Systemic Amyloidosis

Intervention

Drug:
• melphalan
Given PO
• dexamethasone
Given PO
• bortezomib
Given IV

Locations

Country	Name	City	State
United States	Oncare Hawaii Inc-Pali Momi	'Aiea	Hawaii
United States	Pali Momi Medical Center	'Aiea	Hawaii
United States	McFarland Clinic PC-William R Bliss Cancer Center	Ames	Iowa
United States	Cancer Care Center at Island Hospital	Anacortes	Washington
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University/Winship Cancer Institute	Atlanta	Georgia
United States	The Medical Center of Aurora	Aurora	Colorado
United States	Saint Francis Hospital and Health Centers	Beech Grove	Indiana
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Billings Clinic	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies PC	Billings	Montana
United States	Montana Cancer Consortium CCOP	Billings	Montana
United States	Saint Vincent Healthcare	Billings	Montana
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Joseph Medical Center	Bloomington	Illinois
United States	Boston Medical Center	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Boulder Community Hospital	Boulder	Colorado
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington
United States	Highline Medical Center-Main Campus	Burien	Washington
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Graham Hospital Association	Canton	Illinois
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	Rocky Mountain Oncology	Casper	Wyoming
United States	Marshfield Clinic-Chippewa Center	Chippewa Falls	Wisconsin
United States	The Jewish Hospital	Cincinnati	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Case Western Reserve University	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center	Columbus	Ohio
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Dayton CCOP	Dayton	Ohio
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Samaritan North Health Center	Dayton	Ohio
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Colorado Cancer Research Program CCOP	Denver	Colorado
United States	Exempla Saint Joseph Hospital	Denver	Colorado
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Marshfield Clinic Cancer Center at Sacred Heart	Eau Claire	Wisconsin
United States	Fairview-Southdale Hospital	Edina	Minnesota
United States	Union Hospital of Cecil County	Elkton	Maryland
United States	Swedish Medical Center	Englewood	Colorado
United States	Green Bay Oncology - Escanaba	Escanaba	Michigan
United States	Eureka Hospital	Eureka	Illinois
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Unity Hospital	Fridley	Minnesota
United States	Illinois CancerCare Galesburg	Galesburg	Illinois
United States	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	North Colorado Medical Center	Greeley	Colorado
United States	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin
United States	Saint Mary's Hospital	Green Bay	Wisconsin
United States	Saint Vincent Hospital	Green Bay	Wisconsin
United States	Wayne Hospital	Greenville	Ohio
United States	Illinois CancerCare-Havana	Havana	Illinois
United States	Mason District Hospital	Havana	Illinois
United States	Northern Montana Hospital	Havre	Montana
United States	Geisinger Medical Center-Cancer Center Hazelton	Hazleton	Pennsylvania
United States	Saint Peter's Community Hospital	Helena	Montana
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Kuakini Medical Center	Honolulu	Hawaii
United States	Oncare Hawaii Inc-Kuakini	Honolulu	Hawaii
United States	Oncare Hawaii Inc-POB II	Honolulu	Hawaii
United States	OnCare Hawaii-Liliha	Honolulu	Hawaii
United States	Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital	Honolulu	Hawaii
United States	University of Hawaii	Honolulu	Hawaii
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Indiana University Medical Center	Indianapolis	Indiana
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan
United States	Swedish Cancer Institute-Issaquah	Issaquah	Washington
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	Castle Medical Center	Kailua	Hawaii
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Glacier Oncology PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Columbia Basin Hematology and Oncology PLLC	Kennewick	Washington
United States	Kettering Medical Center	Kettering	Ohio
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Gundersen Lutheran	La Crosse	Wisconsin
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Beebe Medical Center	Lewes	Delaware
United States	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Longmont United Hospital	Longmont	Colorado
United States	McKee Medical Center	Loveland	Colorado
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Mcdonough District Hospital	Macomb	Illinois
United States	Holy Family Memorial Hospital	Manitowoc	Wisconsin
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Bay Area Medical Center	Marinette	Wisconsin
United States	Marshfield Clinic	Marshfield	Wisconsin
United States	Providence Milwaukie Hospital	Milwaukie	Oregon
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Montana Cancer Specialists	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Holy Family Medical Center	Monmouth	Illinois
United States	Illinois CancerCare-Monmouth	Monmouth	Illinois
United States	Skagit Valley Hospital	Mount Vernon	Washington
United States	D N Greenwald Center	Mukwonago	Wisconsin
United States	New Ulm Medical Center	New Ulm	Minnesota
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Bromenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center Foundation	Normal	Illinois
United States	Illinois CancerCare-Community Cancer Center	Normal	Illinois
United States	Eastern Connecticut Hematology and Oncology Associates	Norwich	Connecticut
United States	Oconomowoc Memorial Hospital-ProHealth Care Inc	Oconomowoc	Wisconsin
United States	Green Bay Oncology - Oconto Falls	Oconto Falls	Wisconsin
United States	Providence Willamette Falls Medical Center	Oregon City	Oregon
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois
United States	Parker Adventist Hospital	Parker	Colorado
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	Pekin Cancer Treatment Center	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Illinois Oncology Research Association CCOP	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Illinois Valley Hospital	Peru	Illinois
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Adventist Medical Center	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Western Oncology Research Consortium	Portland	Oregon
United States	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Perry Memorial Hospital	Princeton	Illinois
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	Marshfield Clinic at James Beck Cancer Center	Rhinelander	Wisconsin
United States	Marshfield Clinic-Rice Lake Center	Rice Lake	Wisconsin
United States	Reid Hospital and Health Care Services	Richmond	Indiana
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Metro-Minnesota CCOP	Saint Louis Park	Minnesota
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington
United States	Group Health Cooperative-Seattle	Seattle	Washington
United States	Harborview Medical Center	Seattle	Washington
United States	Minor and James Medical PLLC	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	The Polyclinic	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	United General Hospital	Sedro-Woolley	Washington
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Saint Nicholas Hospital	Sheboygan	Wisconsin
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Mercy Medical Center-Sioux City	Sioux City	Iowa
United States	Saint Luke's Regional Medical Center	Sioux City	Iowa
United States	Siouxland Hematology Oncology Associates	Sioux City	Iowa
United States	Providence Hospital	Southfield	Michigan
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	Evergreen Hematology and Oncology PS	Spokane	Washington
United States	Illinois CancerCare-Spring Valley	Spring Valley	Illinois
United States	Memorial Medical Center	Springfield	Illinois
United States	Geisinger Medical Group	State College	Pennsylvania
United States	Marshfield Clinic Cancer Care at Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	North Suburban Medical Center	Thornton	Colorado
United States	Upper Valley Medical Center	Troy	Ohio
United States	Compass Oncology Vancouver	Vancouver	Washington
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Waukesha Memorial Hospital - ProHealth Care	Waukesha	Wisconsin
United States	Wenatchee Valley Medical Center	Wenatchee	Washington
United States	Cleveland Clinic Florida - Weston	Weston	Florida
United States	Diagnostic and Treatment Center	Weston	Wisconsin
United States	Marshfield Clinic - Weston Center	Weston	Wisconsin
United States	Exempla Lutheran Medical Center	Wheat Ridge	Colorado
United States	Geisinger Wyoming Valley	Wilkes-Barre	Pennsylvania
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Clinton Memorial Hospital	Wilmington	Ohio
United States	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin
United States	Minnesota Oncology and Hematology PA-Woodbury	Woodbury	Minnesota
United States	Greene Memorial Hospital	Xenia	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Patients With Hematologic Overall Response (Partial Response [PR]+ Very Good PR [VGPR]+ Amyloid Complete Response [ACR]+ Stringent Complete Response [sCR]) After 3 Months (3 Cycles) of Therapy	sCR: ACR and no clonal cells in bone marrow (BM) ACR: Negative serum/urine immunofixation (IF), <5% plasma cells in BM, and normal serum FLC ratio VGPR: 1. PR and any of the following; 2. serum/urine M-protein detectable by IF but not measurable (NM) on electrophoresis (EP); (3) =90% reduction in serum M-component and urine M-protein <100 mg/24 hr if baseline serum measurable; (4) urine M-component <100 mg/24 hr and NM serum M-protein on serum protein EP if baseline urine measurable; (5) =90% drop in the difference between involved and uninvolved FLC levels if only FLC measurable PR: (1) =50% drop of serum M-protein and 24-hr urinary M-protein drop by =90% or to <200 mg/24 hr if baseline serum/urine measurable; or (2) =50% drop of serum M-protein if only serum measurable at baseline; or (3) 24-hr urinary M-protein drop by =90% or to <200 mg/24 hr if baseline urine measurable; or (4) = 50% drop in the difference between involved and uninvolved FLC if only FLC measu	Assessed at 3 months