A Study Comparing Teclistamab Monotherapy Versus Pomalidomide, Bortezomib, Dexamethasone (PVd) or Carfilzomib, Dexamethasone (Kd) in Participants With Relapsed or Refractory Multiple Myeloma

Relapsed or Refractory Multiple Myeloma Clinical Trial

— MajesTEC-9  

Official title:

A Phase 3 Randomized Study Comparing Teclistamab Monotherapy Versus Pomalidomide, Bortezomib, Dexamethasone (PVd) or Carfilzomib, Dexamethasone (Kd) in Participants With Relapsed or Refractory Multiple Myeloma Who Have Received 1 to 3 Prior Lines of Therapy, Including an Anti-CD38 Monoclonal Antibody and Lenalidomide

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05572515
• Other study ID #: CR109244
• Secondary ID: 64007957MMY30062
• Status: Recruiting
• Phase: Phase 3
• Start date: March 29, 2023
• Est. completion date: August 31, 2031

Study information

• Verified date: April 2024
• Source: Janssen Research & Development, LLC
• Contact: Study Contact
• Phone: 844-434-4210
• Email: Participate-In-This-Study[@]its.jnj.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the efficacy of teclistamab with PVd/Kd.

Description:

Multiple myeloma is an incurable, malignant, plasma cell disorder. Teclistamab (JNJ-64007957) is a full-size, Immunoglobulin G (IgG) 4 proline, alanine, and alanine (PAA) bispecific antibody that targets the cluster of differentiation (CD3) receptor expressed on the surface of T cells and B cell maturation antigen (BCMA). With its dual binding sites, teclistamab is able to draw CD3 positive T cells in close proximity to BCMA positive cells, resulting in T-cell activation and subsequent lysis of BCMA positive cells. Pomalidomide is a third-generation immunomodulatory imide drug (IMiD) that exerts potent, direct tumoricidal and immune-enhancing effects and Carfilzomib is a second-generation proteasome inhibitor that inhibits proteasome which results in disruption of protein turnover and induces apoptosis. The primary hypothesis of this study is that teclistamab monotherapy (Arm A) will significantly improve progression free survival (PFS) compared with investigator's choice of PVd or Kd (Arm B) in participants with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy, including an anti-CD38 monoclonal antibody and lenalidomide. The study will include a screening phase, treatment phase, and follow-up phase. Safety will be assessed by physical examinations, neurologic examinations, eastern cooperative oncology group (ECOG) performance status, clinical laboratory tests, vital signs, and AE monitoring. The overall duration of the study will be up to 9 years.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 590
• Est. completion date: August 31, 2031
• Est. primary completion date: October 14, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Documented diagnosis of multiple myeloma as defined by the criteria below: (a)Multiple myeloma diagnosis according to International Myeloma Working Group (IMWG) diagnostic criteria (b) Measurable disease at screening as defined by any of the following: (1) Serum M-protein level greater than or equal to (>=)0.5 grams per deciliter (g/dL) (central laboratory); or (2) Urine M-protein level >=200 milligrams (mg)/24 hours (central laboratory); or (3) Serum immunoglobulin free light chain >=10 milligrams per deciliter (mg/dL) (central laboratory) and abnormal serum immunoglobulin kappa lambda free light chain ratio
• Received 1 to 3 prior lines of antimyeloma therapy including a minimum of 2 consecutive cycles of an anti- cluster of differentiation 38 (CD38) monoclonal antibody at the approved dosing regimen in any prior line and 2 consecutive cycles of lenalidomide in any prior line
• Documented evidence of progressive disease or failure to achieve a response to last line of therapy based on investigator's determination of response by International myeloma working group (IMWG) criteria
• Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2
• A female participant must agree not to be pregnant, breast-feeding, or plan to become pregnant while enrolled in this study or within 6 months after the last dose of study treatment
• Must be willing and able to adhere to the lifestyle restrictions specified in this protocol

Exclusion Criteria:

• Received any prior B cell maturation antigen (BCMA)-directed therapy
• A participant is not eligible to receive PVd as control therapy if any of the following are present: (1) Received prior pomalidomide therapy, (2) Does not meet criteria for bortezomib retreatment (3) Contraindications or life-threatening allergies, hypersensitivity, or intolerance to pomalidomide or bortezomib, (4) Grade 1 peripheral neuropathy with pain or Grade greater than or equal to (>=) 2 peripheral neuropathy as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0, (5) Received a strong cytochrome P (CYP) 3A4 inducer within 5 half-lives prior to randomization; A participant is not eligible to receive Kd as control therapy if any of the following are present:(1) Received prior carfilzomib therapy, (2) Uncontrolled hypertension, defined as an average systolic blood pressure greater than (>)159 millimeters of mercury (mmHg) or diastolic blood pressure >99 mmHg despite optimal treatment (3) Grade 2 peripheral neuropathy with pain or Grade >=3 peripheral neuropathy as defined by NCI-CTCAE Version 5.0, (4) Contraindications or life-threatening allergies, hypersensitivity, or intolerance to carfilzomib (intolerance defined as prior therapy discontinued due to any adverse event [AE] related to carfilzomib)
• Central nervous system (CNS) involvement or clinical signs of meningeal involvement of multiple myeloma.
• Received a live, attenuated vaccine within 4 weeks before randomization
• Plasma cell leukemia at the time of screening, Waldenstrom's macroglobulinemia, polyneuropathy, organomegaly, endocrinopathy, M-protein (POEMS) syndrome and skin changes, or primary amyloid light chain amyloidosis
• Received a maximum cumulative dose of corticosteroids of >=140 mg of prednisone or equivalent within 14 days prior to randomization

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Relapsed or Refractory Multiple Myeloma

Intervention

Drug:
• Teclistamab
Teclistamab will be administered subcutaneously.
• Pomalidomide
Pomalidomide will be administered orally.
• Bortezomib
Bortezomib will be administered subcutaneously.
• Dexamethasone
Dexamethasone will be administered orally in PVd and intravenously or orally in Kd.
• Carfilzomib
Carfilzomib will be administered intravenously.

Locations

Country	Name	City	State
Australia	Blacktown Hospital	Blacktown
Australia	St. Vincent's Hospital Melbourne	Fitzroy
Australia	Box Hill Hospital	Melbourne
Australia	Fiona Stanley Hospital	Murdoch
Australia	Sir Charles Gairdner Hospital	Nedlands
Austria	LKH - Universitätsklinikum der PMU Salzburg	Salzburg
Austria	Medical University Vienna MUV	Vienna
Belgium	Algemeen Ziekenhuis Klina	Brasschaat
Belgium	Jolimont	Haine-St-Paul
Belgium	Az Groeninge	Kortrijk
Belgium	Universitair Ziekenhuis Gasthuisberg	Leuven
Belgium	CHR de la Citadelle	Liege
Brazil	Hospitais Integradaos da Gavea S/A - DF Star	Brasilia
Brazil	Fundacao Universidade de Caxias do Sul	Caxias do Sul
Brazil	Liga Paranaense de Combate ao Cancer	Curitiba
Brazil	Instituto Joinvilense de Hematologia e Oncologia Ltda-Centro de Hematologia e Oncologia	Joinville
Brazil	Liga Norte Riograndense Contra O Cancer	Natal
Brazil	Complexo Hospitalar de Niteroi	Niteroi
Brazil	Instituto de Educacao, Pesquisa e Gestao em Saude Instituto Americas (COI)	Rio de Janeiro
Brazil	Hospital Sao Rafael	Salvador
Brazil	Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto - Hospital de Base	Sao Jose do Rio Preto
Brazil	Fundacao Antonio Prudente A C Camargo Cancer Center	Sao Paulo
Brazil	Instituto D Or de Pesquisa e Ensino (IDOR)	Sao Paulo
Brazil	Sociedade Beneficente de Senhoras - Hospital Sírio Libanês	Sao Paulo
Brazil	Clinica Sao Germano	São Paulo
Brazil	Hospital Alemao Oswaldo Cruz	São Paulo
Brazil	Real e Benemérita Associação Portuguesa de Beneficência	São Paulo
Brazil	Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein	São Paulo
Canada	Brampton Civic Hospital	Brampton	Ontario
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	CIUSSS de l'Est-de-l'Île-de-Montréal Installation Hôpital Maisonneuve-Rosemont	Montreal	Quebec
Canada	Lakeridge Health Oshawa	Oshawa	Ontario
Canada	Saint John Regional Hospital	Saint John	New Brunswick
China	Beijing Chaoyang Hospital	Beijing
China	BeiJing JiShuiTan Hospital	Beijing
China	The First Bethune Hospital of Jilin University	Changchun
China	The Third Xiangya Hospital, Central South University	Changsha
China	Sichuan Provincial Peoples Hospital	Chengdu
China	Chongqing University Cancer Hospital	Chongqing
China	Fujian Meidical University Union Hospital	Fu Zhou
China	Sun Yat -Sen University Cancer Center	Guangzhou
China	First affiliated Hospital of Zhejiang University	Hangzhou
China	Harbin medical university cancer hospital	Harbin
China	The First Affiliated Hospital of NanChang University	Nanchang
China	Nanjing Drum Tower Hospital	Nanjing
China	First Affiliated Hospital of Guangxi Medical University	Nanning
China	Shanghai Fourth People s Hospital	Shanghai
China	Shengjing Hospital of China Medical University	Shenyang
China	Shenzhen 2nd People's Hospital	Shenzhen
China	Institute of Hematology and Blood Diseases Hospital	Tian Jin
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin
China	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou
China	Wuhan Union Hospital	Wuhan
China	Wuxi People s Hospital	Wuxi
China	The Second Affiliated Hospital of Xi'an Jiaotong University	Xi'an
China	Henan Cancer Hospital	Zhengzhou
Czechia	Fakultni nemocnice Brno	Brno
Czechia	Fakultní nemocnice Olomouc	Olomouc
Czechia	Fakultni nemocnice Ostrava	Ostrava - Poruba
Czechia	Vseobecna fakultni nemocnice v Praze	Praha 2
Denmark	Aalborg University Hospital	Aalborg
Denmark	Aarhus University Hospital	Aarhus
Denmark	Rigshospitalet	Copenhagen
Denmark	Regionshospitalet Godstrup	Herning
Denmark	Odense Universitetshospital	Odense C
Denmark	Vejle Sygehus	Vejle
France	CHU Amiens - Hopital Sud	AMIENS cedex 1
France	Hôpital Côte de Nacre	Caen cedex 9
France	CHU Grenoble	Grenoble
France	Centre Hospitalier du Mans	Le Mans
France	Hopital Saint Vincent de Paul	Lille
France	CHU de Montpellier, Hopital Saint-Eloi	Montpellier
France	CHU Nantes	Nantes Cedex 1
France	Hopital de la Pitie Salpetriere	Paris
France	Hôpital Necker Enfants Malades	Paris
France	Hopital Saint-Antoine	Paris
France	Institut Universitaire du Cancer Toulouse Oncopole	Toulouse
France	CHU de Nancy - Hopital de Brabois	Vandœuvre-lès-Nancy
Germany	Carl-Thiem-Klinikum Cottbus gGmbH	Cottbus
Germany	Universitatsklinikum Carl Gustav Carus Dresden	Dresden
Germany	Universitätsmedizin Greifswald	Greifswald
Germany	Asklepios Klinik Altona	Hamburg
Germany	Universitaetsklinikum Heidelberg	Heidelberg
Germany	Universitaetsklinikum Giessen und Marburg GmbH	Marburg
Germany	Universitatsklinikum Tubingen	Tübingen
Germany	Universitatsklinikum Ulm	Ulm
Germany	Heinrich-Braun-Klinikum gGmbH	Zwickau
Greece	Alexandra General Hospital of Athens	Athens Attica
Greece	Agios Andreas General Hospital of Patra	Patra
Greece	G Papanikolaou Hospital of Thessaloniki	Thessaloniki
India	Fortis Memorial Research Institute	Gurgaon
India	Deenanath Mangeshkar Hospital and Research Centre	Pune
Israel	Hillel Yaffe Medical Center	Hadera
Israel	Bnai Zion Medical Center	Haifa
Israel	Carmel Medical Center	Haifa
Israel	Rabin Medical Center	Petah Tikva
Israel	Sheba Medical Center	Ramat Gan
Israel	Tel-Aviv Sourasky Medical Center	Tel Aviv-Yafo
Italy	A O U Sant Orsola Malpighi	Bologna
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano
Italy	Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone	Palermo
Italy	Ospedale Santa Chiara AO Universitaria Pisana	Pisa
Italy	Arcispedale Santa Maria Nuova - IRCCS	Reggio Emilia
Italy	Campus Bio Medico di Roma	Roma
Italy	A O Universitaria Senese Ospedale Santa Maria alle Scotte	Siena
Italy	A.O.U. Citta della Salute e della Scienza di Torino - Presidio Molinette	Turin
Italy	ASUI Santa Maria della Misericordia di Udine	Udine
Italy	Ospedale di Circolo e Fondazione Macchi	Varese
Japan	Chiba Cancer Center	Chiba
Japan	Ogaki Municipal Hospital	Gifu
Japan	National Hospital Organization Shibukawa Medical Center	Gunma
Japan	Kansai Medical University Hospital	Hirakata
Japan	Hitachi General Hospital	Hitachi
Japan	Saitama Medical University Hospital	Iruma-gun
Japan	Kameda General Hospital	Kamogawa City
Japan	National Cancer Center Hospital East	Kashiwa
Japan	Kurashiki Central Hospital	Kurashiki
Japan	Matsuyama Red Cross Hospital	Matsuyama
Japan	Aichi Medical University Hospital	Nagakute
Japan	JRC Nagasaki Genbaku Hospital	Nagasaki-Shi
Japan	Niigata University Medical And Dental Hospital	Niigata
Japan	National Hospital Organization Okayama Medical Center	Okayama
Japan	Osaka Metropolitan University Hospital	Osaka
Japan	Hokkaido University Hospital	Sapporo
Japan	Juntendo University Hospital	Tokyo
Japan	The Cancer Institute Hospital of JFCR	Tokyo
Japan	Yamagata University Hospital	Yamagata
Japan	Yamanashi Prefectural Central Hospital	Yamanashi
Malaysia	Hospital Pulau Pinang	Georgetown
Malaysia	Hospital Queen Elizabeth	Kota Kinabalu
Malaysia	University Malaya Medical Centre	Kuala Lumpur
Malaysia	Subang Jaya Medical Centre	Subang Jaya
Netherlands	Meander Medisch Centrum	Amersfoort
Netherlands	VUMC Amsterdam	Amsterdam
Netherlands	Universitair Medisch Centrum Groningen	Groningen
Netherlands	UMC Utrecht	Utrecht
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Pratia Onkologia Katowice	Katowice
Poland	Swietokrzyskie Centrum Onkologii SPZOZ w Kielcach	Kielce
Poland	Uniwersytecki Szpital Kliniczny Nr 1 w Lublinie	Lublin
Portugal	Hosp. Garcia de Orta	Almada
Portugal	Ccab - Hosp. de Braga	Braga
Portugal	Champalimaud Foundation Champalimaud Centre	Lisbon
Portugal	Instituto Portugues de Oncologia	Porto
Portugal	Hospital de Vila Nova de Gaia E.P.E.	Vila Nova de Gaia
Spain	Hosp. Univ. Germans Trias I Pujol	Badalona
Spain	Institut Catala d'Oncologia L'Hospitalet	Hospitalet de Llobregat
Spain	Hosp. de Jerez de La Frontera	Jerez de la Frontera
Spain	Hosp. de Leon	Leon
Spain	Hosp. Univ. 12 de Octubre	Madrid
Spain	Hosp. Univ. Infanta Leonor	Madrid
Spain	Hosp. Univ. Ramon Y Cajal	Madrid
Spain	Hosp. Gral. Univ. J.M. Morales Meseguer	Murcia
Spain	Hospital Universitario Central de Asturias	Oviedo
Spain	Hosp. Son Llatzer	Palma de Mallorca
Spain	Hosp. Montecelo	Pontevedra
Spain	Hosp. Quiron Madrid Pozuelo	Pozuelo de Alarcon
Spain	Hospital Universitari i Politecnic La Fe	València
Sweden	Falu Lasarett Medicinkliniken Falun	Falun
Sweden	Helsingborgs lasarett	Helsingborg
Sweden	Akademiska Sjukhuset	Uppsala
Turkey	Ankara Gulhane Training and Research Hospital	Ankara
Turkey	Ankara University Medical Faculty	Ankara
Turkey	Dr Abdurrahman Yurtaslan Oncology Training and Research Hospital	Ankara
Turkey	Liv Hospital Ankara	Ankara
Turkey	Antalya Training And Research Hospital	Antalya
Turkey	Ondokuz Mayis University	Atakum
Turkey	Pamukkale University Medical Faculty	Denizli
Turkey	Medipol University Hospital	Istanbul
United Kingdom	Aberdeen Royal Infirmary	Aberdeen
United Kingdom	University Hospitals Birmingham NHS Foundation Trust	Birmingham
United Kingdom	Colchester Hospital University NHS	Colchester
United Kingdom	The Clatterbridge Cancer Centre	Liverpool
United Kingdom	Chelsea And Westminster Hospital	London
United Kingdom	St George's Hospital	London
United Kingdom	Norfolk and Norwich University Hospital	Norwich
United States	Alaska Oncology and Hematology LLC	Anchorage	Alaska
United States	Alta Bates Comprehensive Cancer Center	Berkeley	California
United States	Boston University Medical Center	Boston	Massachusetts
United States	Cooper Health System MD Anderson Cancer Center at Cooper	Camden	New Jersey
United States	Saint Luke's Hospital - Saint Luke's Cancer Specialists	Chesterfield	Missouri
United States	Durham VAMC	Durham	North Carolina
United States	University of Connecticut	Farmington	Connecticut
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	Baylor College of Medicine	Houston	Texas
United States	Penn Medicine Lancaster General Health	Lancaster	Pennsylvania
United States	MemorialCare Long Beach Medical Center	Long Beach	California
United States	East Jefferson General Hospital Bone Marrow Transport Clinic	Metairie	Louisiana
United States	University of Miami Sylvester Cancer Center	Miami	Florida
United States	Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center	New York	New York
United States	University of California Irvine	Orange	California
United States	Orlando Health Cancer Institute	Orlando	Florida
United States	Utah Cancer Specialists	Salt Lake City	Utah
United States	Cleveland Clinic Florida	Weston	Florida
United States	PIH Health Hospital	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  Canada,  China,  Czechia,  Denmark,  France,  Germany,  Greece,  India,  Israel,  Italy,  Japan,  Malaysia,  Netherlands,  Poland,  Portugal,  Spain,  Sweden,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS)	PFS is defined as the time from the date of randomization to the date of first documented disease progression, as defined in the International myeloma working group (IMWG) 2016 response criteria, or death due to any cause, whichever occurs first.	Up to 9 years
Secondary	Overall Response (Partial Response [PR] or Better)	Overall response (PR or better) is defined as participants who have a PR or better prior to subsequent antimyeloma therapy in accordance with the IMWG 2016 criteria.	Up to 9 years
Secondary	Very Good Partial Response (VGPR) or Better Response	VGPR or better (Stringent Complete Response [sCR]+Complete Response [CR]+VGPR) is defined as participants who achieve a VGPR or better response prior to subsequent antimyeloma therapy in accordance with the IMWG 2016 criteria.	Up to 9 years
Secondary	Complete Response (CR) or Better Response	CR or better response is defined as participants who achieve a CR or better response prior to subsequent antimyeloma therapy in accordance with the IMWG 2016 criteria.	Up to 9 years
Secondary	Duration of Response (DOR)	DOR is defined as the time interval between the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease according to the IMWG 2016 response criteria or death due to any cause, whichever occurs first.	Up to 9 years
Secondary	Time to Next Treatment (TTNT)	TTNT is defined as the time from randomization to the start of subsequent antimyeloma treatment.	Up to 9 years
Secondary	Progression-free Survival on Next-line Therapy (PFS2)	PFS2 is defined as the time interval between the date of randomization and date of event, which is defined as progressive disease as assessed by investigator on the first subsequent line of antimyeloma therapy, or death from any cause, whichever occurs first.	Up to 9 years
Secondary	Overall Survival (OS)	OS is defined as the time from the date of randomization to the date of the participant's death due to any cause.	Up to 9 years
Secondary	Number of Participants with Adverse Events (AEs) by Severity	Number of participants with AEs by Severity will be reported.	Up to 9 years
Secondary	Number of Participants with Serious Adverse Events (SAEs) by Severity	Number of participants with SAEs by Severity will be reported.	Up to 9 years
Secondary	Number of Participants with Abnormal Laboratory Results	Number of participants with abnormal laboratory results (such as hematology and chemistry) will be reported.	Up to 9 years
Secondary	Serum Concentrations of Teclistamab	Serum concentrations of teclistamab will be reported.	Up to 9 years
Secondary	Number of Participants with Anti-drug Antibodies (ADAs) to Teclistamab	Number of participants with ADAs to teclistamab will be reported.	Up to 9 years
Secondary	Change from Baseline in Symptoms, Functioning, and Overall Health-related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC-QLQ-C30)	Change from baseline in symptoms, functioning, and overall HRQoL assessed by EORTC QLQ-C30 score version 3 will be reported. The EORTC- QLQ-C30 Version 3 includes 30 items that make up 5 functional scales (physical, role, emotional, cognitive, and social), 1 global health status scale, 3 symptom scales (pain, fatigue, and nausea/vomiting), and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The item and scale scores are transformed to a 0 to 100 scale. A high scale score represents a higher response level. Thus, a high score for a functional scale represents a high/healthy level of functioning and a high score for the global health status represents high HRQoL, but a high score for a symptom scale/item represents a high level of symptomatology/problems.	Baseline up to 9 years
Secondary	Change from Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q) Scale Score	Change from baseline in symptoms, functioning, and overall HRQoL assessed by MySIm-Q will be reported. The MySIm-Q is a disease-specific PRO assessment complementary to the EORTC-QLQ-C30. It includes 17 items resulting in a symptom subscale and an impact subscale. The recall period is the "past 7 days", and responses are reported on a 5-point verbal rating scale.	Baseline up to 9 years
Secondary	Change from Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)	Change from baseline in symptoms, functioning, and overall HRQoL assessed by PRO-CTCAE will be reported. The National Cancer Institute's (NCI's) PRO-CTCAE is an item library of common adverse events experienced by people with cancer that are appropriate for self-reporting of treatment tolerability. Each symptom selected for inclusion can be rated by up to 3 attributes characterizing the presence/frequency, severity, and/or interference of the AEs. It ranges from 0 to 4 with higher scores indicating higher frequency or greater severity/impact.	Baseline up to 6 months
Secondary	Change from Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by EuroQol Five Dimension Questionnaire 5-Level (EQ-5D-5L)	Change from baseline in symptoms, functioning, and overall HRQoL assessed by EQ-5D-5L will be reported. The EQ-5D-5L is a generic measure of health status. The EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).	Baseline up to 9 years
Secondary	Time to Worsening in Symptoms, Functioning, and Overall HRQoL	Time to worsening in symptoms, functioning, and overall HRQoL will be measured as the interval from the date of randomization to the start date of meaningful change.	Up to 9 years
Secondary	PFS in Participants in High-risk Molecular Features	PFS in participants in high-risk molecular features will be reported. PFS is defined as the time from the date of randomization to the date of first documented disease progression, as defined in the IMWG 2016 response criteria, or death due to any cause, whichever occurs first.	Up to 9 years
Secondary	Depth of Response in Participants in High-risk Molecular Features	Depth of response in participants in high-risk molecular features will be reported.	Up to 9 years