MMyBRave: Multiple Myeloma (MM) Profile in Brazil: A Retrospective Observational Analysis

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03506386
• Collaborator: (none)
• Enrollment: 943
• Locations: 17
• Actual Duration (Months): 17.6
• Patients Per Site: 55.5
• Patients Per Site Per Month: 3.1

Study Details

Study Description

Brief Summary

The purpose of this study is to present a descriptive analysis of demographic and clinical characteristics of the participants, as well as of the treatment patterns for multiple myeloma (MM) in Brazil.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Other: No Intervention

Detailed Description

Participants with a diagnosis of MM will be observed in this retrospective study. Data collected for the study will include identification, demographic, baseline data on MM, additional baseline laboratory, initial treatment for MM, subsequent treatment for MM, and outcome.

The study will enroll approximately 1000 participants.

This multi-center trial will be conducted in five geographic regions of Brazil. For each participant, data collection will comprise the longest possible period of time since the diagnosis of MM (within the eligibility window of time, between January 1, 2008 and December 31, 2016) and the cut-off date for data collection (December 31, 2016), unless a participant has died or been lost to follow-up before that. The study is planned to last for approximately 24 months since its initiation (initiation defined as the initiation visit for the first site).

Study Design

• Study Type: Observational
• Actual Enrollment: 943 participants
• Observational Model: Cohort
• Time Perspective: Retrospective
• Official Title: Multiple Myeloma Profile in Brazil: A Retrospective Observational Analysis
• Actual Study Start Date: Aug 9, 2018
• Actual Primary Completion Date: Nov 8, 2019
• Actual Study Completion Date: Jan 27, 2020

Arms and Interventions

Arm	Intervention/Treatment
Multiple Myeloma Participants Participants with multiple myeloma (MM) were observed retrospectively since the diagnosis up to death or lost to follow-up within the eligibility window of time (between January 1, 2008 and December 31, 2016), in this study.	Other: No Intervention; As it was an observational study, no intervention was administered.

Outcome Measures

Primary Outcome Measures

1. Number of Multiple Myeloma (MM) Participants Categorized by Clinical Characteristics [From initial diagnosis up to end of follow up treatment or to the retrospective cut-off date within the time of interest (between January 1, 2008, and December 31, 2016) [approximately 11.7 years]]

   MM clinical characteristics upon diagnosis were classified by eligibility criteria for transplantation (eligible/not eligible) and included: presence of plasma cells in the bone marrow by biopsy and aspiration, bone or extramedullary biopsy, plasma cells determined by immunohistochemistry (Yes/No/Unknown), plasma cells determined by flow cytometry (Yes/No/Unknown) hypercalcemia, renal failure, anemia, and bone lesions features (more than one focal lesion on magnetic resonance imaging (MRI) that is at least 5 mm or greater in size), presence of monoclonal proteins (immunoglobulin (Ig)G, IgG kappa, IgG lambda, IgA, IgA kappa, IgA lambda, kappa only, lambda only, IgD, IgE, IgM, Non-secretory and Unknown), free light chain ratio (serum involved / uninvolved free light chain ratio of 100 or greater, provided the absolute level of the involved light chain is at least 100 mg/L). Only categories with data are reported. Participants were counted multiple times in different categories.

2. Number of Multiple Myeloma (MM) Participants Categorized by Treatment Patterns [From initial diagnosis up to end of follow up treatment or to the retrospective cut-off date within the time of interest (between January 1, 2008, and December 31, 2016) [approximately 11.7 years]]

   Treatment patterns were collected from institutional charts [included public institution, private institution and both (90% public and 10% private) institutions] of participants in Brazil. The treatment patterns were collected as induction treatment, consolidation treatment, maintenance treatment performed at Baseline (at initial diagnosis) and as a induction treatment, maintenance treatment and type of treatment performed after transplantation, for second to tenth line of treatment. Only categories with data are reported. Participants were counted multiple times in different categories.

Secondary Outcome Measures

1. Overall Survival (OS) [From the date of diagnosis up to death within the period of interest (between January 1, 2008, and December 31, 2016) or up to the end of this study [up to 11.7 years]]

   Overall survival was defined as the time elapsed between the date of diagnosis until death, with censoring of participants who were alive when last seen or who lost to follow up.

2. Duration of Treatment [From treatment initiation up to discontinuation of treatment or lost to follow-up, whichever occurs first up to the end of this study (up to 11.7 years)]

   Duration of treatment was defined with respect to selected lines or regimens of interest, considering the time elapsed from each treatment initiation to discontinuation, and censoring participants who lost to follow-up before discontinuation. Duration of treatment was classified by participants eligibility- eligible/not eligible for transplantation. The deaths occurred after treatment initiation to end of study are reported in categories 'Since Diagnosis to Death-Eligible and Not Eligible'.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Provision of written informed consent, for participants who are alive and not lost to follow-up (for participants already deceased or lost follow up, informed consent should have been waived by the corresponding ethics review board [ERB]).

2. Documented diagnosis of MM by the responsible physician between January 1, 2008, and December 31, 2016.

3. Absence of any plasma-cell disorder other than MM.

4. Absence of any immunoglobulin-related disorder other than MM.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Centro de Hematologia e Oncologia (CEHON)	Salvador	BA	Brazil	40110-150
2	Hospital Sao Rafael	Salvador	BA	Brazil	41253-190
3	Hospital das Clinicas da UFG	Goiania	GO	Brazil	74605-020
4	Hospital das Clinicas da UFMG	Belo Horizonte	MG	Brazil	30130-100
5	Fundacao IMEPEN	Juiz de Fora	MG	Brazil	36036-330
6	Clinica de Tratamento e Pesquisa em Hematologia LTDA.	Cuiaba	Mount	Brazil	78055-000
7	Hospital das Clinicas da UFPR	Curitiba	PR	Brazil	80060-900
8	CIONC - Centro Integrado de Oncologia de Curitiba	Curitiba	PR	Brazil	80810-050
9	Universidade Federal do Rio de Janeiro	Rio de Janeiro	RJ	Brazil	21941-590
10	Hospital Sao Vicente de Paulo	Passo Fundo	RS	Brazil	99010-080
11	Hospital de Clinicas de Porto Alegre	Porto Alegre	RS	Brazil	90035-903
12	Centro de Pesquisas Oncologicas (CEPON)	Florianopolis	SC	Brazil	88034-000
13	Hospital Amaral Carvalho	Jau	SP	Brazil	17210-080
14	Hospital do Servidor Publico de SP	Sao Paulo	SP	Brazil	04029-000
15	Clinica Sao Germano	Sao Paulo	SP	Brazil	04537-081
16	Hospital das Clinicas da FMUSP	Sao Paulo	SP	Brazil	05403-000
17	Casa de Saude Santa Marcelina	Sao Paulo	SP	Brazil	08270-060

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Medical Monitor Clinical Science, Takeda

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 12, 2018

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT03506386
• Other Study ID Numbers: NDMM-5004
• First Posted: Apr 24, 2018
• Last Update Posted: Feb 8, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Takeda: Real World Evidence , Multiple Myeloma Profile, Brazil
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 17 investigative sites in Brazil from 9 August 2018 to 27 January 2020.
Pre-assignment Detail	Participants with a diagnosis of Multiple Myeloma (MM) were observed to collect data retrospectively between eligibility window: 1 January 2008 to 31 December 2016, in this study.

Arm/Group Title	Multiple Myeloma Participants
Arm/Group Description	Participants with MM were observed retrospectively since the diagnosis up to death or lost to follow-up within the eligibility window of time (between January 1, 2008 and December 31, 2016), in this study.
Period Title: Overall Study
STARTED	943
COMPLETED	943
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Multiple Myeloma Participants
Arm/Group Description	Participants with MM were observed retrospectively since the diagnosis up to death or lost to follow-up within the eligibility window of time (between January 1, 2008 and December 31, 2016), in this study.
Overall Participants	943
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.4 (11.9)
Sex: Female, Male (Count of Participants)
Female	437 46.3%
Male	506 53.7%
Race/Ethnicity, Customized (Count of Participants)
White	576 61.1%
Pardo (Mixed Race or Mulatto)	142 15.1%
Black	63 6.7%
Asian	4 0.4%
Indigenous Person	1 0.1%
Unknown	157 16.6%
Region of Enrollment (Count of Participants)
Brazil	943 100%

Outcome Measures

1. Primary Outcome

Title	Number of Multiple Myeloma (MM) Participants Categorized by Clinical Characteristics
Description	MM clinical characteristics upon diagnosis were classified by eligibility criteria for transplantation (eligible/not eligible) and included: presence of plasma cells in the bone marrow by biopsy and aspiration, bone or extramedullary biopsy, plasma cells determined by immunohistochemistry (Yes/No/Unknown), plasma cells determined by flow cytometry (Yes/No/Unknown) hypercalcemia, renal failure, anemia, and bone lesions features (more than one focal lesion on magnetic resonance imaging (MRI) that is at least 5 mm or greater in size), presence of monoclonal proteins (immunoglobulin (Ig)G, IgG kappa, IgG lambda, IgA, IgA kappa, IgA lambda, kappa only, lambda only, IgD, IgE, IgM, Non-secretory and Unknown), free light chain ratio (serum involved / uninvolved free light chain ratio of 100 or greater, provided the absolute level of the involved light chain is at least 100 mg/L). Only categories with data are reported. Participants were counted multiple times in different categories.
Time Frame	From initial diagnosis up to end of follow up treatment or to the retrospective cut-off date within the time of interest (between January 1, 2008, and December 31, 2016) [approximately 11.7 years]

Outcome Measure Data

Analysis Population Description

All participants eligible for analyses were included. Number analyzed are the participants with data available for analyses of the specific category.

Arm/Group Title	Multiple Myeloma Participants
Arm/Group Description	Participants with MM were observed retrospectively since the diagnosis up to death or lost to follow-up within the eligibility window of time (between January 1, 2008 and December 31, 2016), in this study.
Measure Participants	943
Bone Marrow Biopsy: Eligible	342 36.3%
Bone Marrow Biopsy: Not Eligible	366 38.8%
Bone Marrow Aspiration: Eligible	48 5.1%
Bone Marrow Aspiration: Not Eligible	36 3.8%
Bone or Extramedullary Biopsy: Eligible	232 24.6%
Bone or Extramedullary Biopsy: Not Eligible	241 25.6%
Immunohistochemistry Performed: Yes: Eligible	161 17.1%
Immunohistochemistry Performed: Yes: Not Eligible	142 15.1%
Immunohistochemistry Performed: No: Eligible	245 26%
Immunohistochemistry Performed: No: Not Eligible	281 29.8%
Immunohistochemistry Performed: Unknown: Eligible	46 4.9%
Immunohistochemistry Performed: Unknown: Not Eligible	68 7.2%
Flow Cytometry Performed: Yes: Eligible	136 14.4%
Flow Cytometry Performed: Yes: Not Eligible	130 13.8%
Flow Cytometry Performed: No: Eligible	254 26.9%
Flow Cytometry Performed: No: Not Eligible	293 31.1%
Flow Cytometry Performed: Unknown: Eligible	62 6.6%
Flow Cytometry Performed: Unknown: Not Eligible	67 7.1%
MM Diagnosis Definition: Bone Lesion: Eligible	15 1.6%
MM Diagnosis Definition: Bone Lesion: Not Eligible	35 3.7%
MM Diagnosis Definition: Anemia: Eligible	354 37.5%
MM Diagnosis Definition: Anemia: Not Eligible	342 36.3%
MM Diagnosis Definition: Hypercalcemia: Eligible	286 30.3%
MM Diagnosis Definition: Hypercalcemia: Not Eligible	343 36.4%
MM Diagnosis Definition: Renal failure: Eligible	70 7.4%
MM Diagnosis Definition: Renal failure: Not Eligible	74 7.8%
MM Diagnosis Definition:Serum Involved/Uninvolved Free Light Chain Ratio of >=100:Eligible	80 8.5%
MM Diagnosis Definition:Serum Involved/Uninvolved Free Light Chain Ratio of >=100:Not Eligible	125 13.3%
MM Diagnosis Definition: >1 Focal Lesion on MRI That is >=5mm in Size: Eligible	4 0.4%
MM Diagnosis Definition: >1 Focal Lesion on MRI That is >=5mm in Size: Not Eligible	17 1.8%
Monoclonal Component: IgG: Eligible	31 3.3%
Monoclonal Component: IgG: Not Eligible	34 3.6%
Monoclonal Component: IgG Kappa: Eligible	138 14.6%
Monoclonal Component: IgG Kappa: Not Eligible	152 16.1%
Monoclonal Component: IgG Lambda: Eligible	47 5%
Monoclonal Component: IgG Lambda: Not Eligible	55 5.8%
Monoclonal Component: IgA: Eligible	18 1.9%
Monoclonal Component: IgA: Not Eligible	17 1.8%
Monoclonal Component: IgA Kappa: Eligible	40 4.2%
Monoclonal Component: IgA Kappa: Not Eligible	37 3.9%
Monoclonal Component: IgA Lambda: Eligible	32 3.4%
Monoclonal Component: IgA Lambda: Not Eligible	24 2.5%
Monoclonal Component: Kappa Only: Eligible	38 4%
Monoclonal Component: Kappa Only: Not Eligible	42 4.5%
Monoclonal Component: Lambda Only: Eligible	32 3.4%
Monoclonal Component: Lambda Only: Not Eligible	22 2.3%
Monoclonal Component: IgE: Eligible	1 0.1%
Monoclonal Component: IgE: Not Eligible	0 0%
Monoclonal Component: IgM: Eligible	2 0.2%
Monoclonal Component: IgM: Not Eligible	2 0.2%
Monoclonal Component: Non-secretory: Eligible	18 1.9%
Monoclonal Component: Non-secretory: Not Eligible	10 1.1%
Monoclonal Component: Unknown: Eligible	55 5.8%
Monoclonal Component: Unknown: Not Eligible	96 10.2%

2. Primary Outcome

Title	Number of Multiple Myeloma (MM) Participants Categorized by Treatment Patterns
Description	Treatment patterns were collected from institutional charts [included public institution, private institution and both (90% public and 10% private) institutions] of participants in Brazil. The treatment patterns were collected as induction treatment, consolidation treatment, maintenance treatment performed at Baseline (at initial diagnosis) and as a induction treatment, maintenance treatment and type of treatment performed after transplantation, for second to tenth line of treatment. Only categories with data are reported. Participants were counted multiple times in different categories.
Time Frame	From initial diagnosis up to end of follow up treatment or to the retrospective cut-off date within the time of interest (between January 1, 2008, and December 31, 2016) [approximately 11.7 years]

Outcome Measure Data

Analysis Population Description

All participants eligible for analyses were included. Number analyzed are the number of participants with evaluable data for given category.

Arm/Group Title	Multiple Myeloma Participants
Arm/Group Description	Participants with MM were observed retrospectively since the diagnosis up to death or lost to follow-up within the eligibility window of time (between January 1, 2008 and December 31, 2016), in this study.
Measure Participants	922
Public Institution	394 41.8%
Private Institution	456 48.4%
Both (90% public and 10% private) Institutions	66 7%
Public Institution	3 0.3%
Private Institution	14 1.5%
Both (90% public and 10% private) Institutions	0 0%
Public Institution	39 4.1%
Private Institution	32 3.4%
Both (90% public and 10% private) Institutions	5 0.5%
Public Institution	230 24.4%
Private Institution	236 25%
Both (90% public and 10% private) Institutions	29 3.1%
Public Institution	22 2.3%
Private Institution	9 1%
Both (90% public and 10% private) Institutions	4 0.4%
Public Institution	7 0.7%
Private Institution	6 0.6%
Both (90% public and 10% private) Institutions	1 0.1%
Public Institution	142 15.1%
Private Institution	131 13.9%
Both (90% public and 10% private) Institutions	11 1.2%
Public Institution	13 1.4%
Private Institution	3 0.3%
Both (90% public and 10% private) Institutions	2 0.2%
Public Institution	2 0.2%
Private Institution	1 0.1%
Both (90% public and 10% private) Institutions	0 0%
Public Institution	70 7.4%
Private Institution	70 7.4%
Both (90% public and 10% private) Institutions	6 0.6%
Public Institution	3 0.3%
Private Institution	2 0.2%
Both (90% public and 10% private) Institutions	1 0.1%
Public Institution	0 0%
Private Institution	1 0.1%
Both (90% public and 10% private) Institutions	0 0%
Public Institution	38 4%
Private Institution	37 3.9%
Both (90% public and 10% private) Institutions	3 0.3%
Public Institution	1 0.1%
Private Institution	2 0.2%
Both (90% public and 10% private) Institutions	0 0%
Public Institution	0 0%
Private Institution	1 0.1%
Both (90% public and 10% private) Institutions	0 0%
Public Institution	21 2.2%
Private Institution	19 2%
Both (90% public and 10% private) Institutions	1 0.1%
Public Institution	2 0.2%
Private Institution	0 0%
Both (90% public and 10% private) Institutions	0 0%
Public Institution	6 0.6%
Private Institution	10 1.1%
Both (90% public and 10% private) Institutions	0 0%
Public Institution	3 0.3%
Private Institution	2 0.2%
Both (90% public and 10% private) Institutions	0 0%
Public Institution	1 0.1%
Private Institution	2 0.2%
Both (90% public and 10% private) Institutions	0 0%
Public Institution	1 0.1%
Private Institution	1 0.1%
Both (90% public and 10% private) Institutions	0 0%

3. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival was defined as the time elapsed between the date of diagnosis until death, with censoring of participants who were alive when last seen or who lost to follow up.
Time Frame	From the date of diagnosis up to death within the period of interest (between January 1, 2008, and December 31, 2016) or up to the end of this study [up to 11.7 years]

Outcome Measure Data

Analysis Population Description

All participants eligible for analyses who had non-missing observations were analyzed. Number analyzed is the number of participants with data available for given category.

Arm/Group Title	Multiple Myeloma Participants
Arm/Group Description	Participants with MM were observed retrospectively since the diagnosis up to death or lost to follow-up within the eligibility window of time (between January 1, 2008 and December 31, 2016), in this study.
Measure Participants	922
Eligible for Transplantation but not Performed	1926
Eligible for Transplantation and Performed	3277
Not Eligible for Transplantation	1566

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Multiple Myeloma Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Statistical differences among eligible performed, eligible not performed and not eligible participants were estimated by Log Rank test.
	Method	Log Rank
	Comments

4. Secondary Outcome

Title	Duration of Treatment
Description	Duration of treatment was defined with respect to selected lines or regimens of interest, considering the time elapsed from each treatment initiation to discontinuation, and censoring participants who lost to follow-up before discontinuation. Duration of treatment was classified by participants eligibility- eligible/not eligible for transplantation. The deaths occurred after treatment initiation to end of study are reported in categories 'Since Diagnosis to Death-Eligible and Not Eligible'.
Time Frame	From treatment initiation up to discontinuation of treatment or lost to follow-up, whichever occurs first up to the end of this study (up to 11.7 years)

Outcome Measure Data

Analysis Population Description

All participants eligible for analyses who had non-missing observations were analyzed. Number analyzed is the number of participants with data available for given category.

Arm/Group Title	Multiple Myeloma Participants
Arm/Group Description	Participants with MM were observed retrospectively since the diagnosis up to death or lost to follow-up within the eligibility window of time (between January 1, 2008 and December 31, 2016), in this study.
Measure Participants	922
Since Diagnosis for Living Participants: Eligible	5
Since Diagnosis for Living Participants: Not Eligible	4.2
Since Diagnosis to Lost to Follow-up: Eligible	3.6
Since Diagnosis to Lost to Follow-up: Not Eligible	2.3
Since Diagnosis to Death: Eligible	2.8
Since Diagnosis to Death: Not Eligible	1.8

Adverse Events

Time Frame	From diagnosis up to the end of this study (up to 11.7 years)
Adverse Event Reporting Description	Only deaths were collected, and data of adverse events or adverse drug reactions were not collected as part of the study database.
Arm/Group Title	Multiple Myeloma Participants
Arm/Group Description	Participants with MM were observed retrospectively since the diagnosis up to death or lost to follow-up within the eligibility window of time (between January 1, 2008 and December 31, 2016), in this study.
All Cause Mortality
	Multiple Myeloma Participants
	Affected / at Risk (%)	# Events
Total	436/943 (46.2%)
Serious Adverse Events
	Multiple Myeloma Participants
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Multiple Myeloma Participants
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.