Evaluating early intervention in smoldering myeloma clinical trials: a systematic review.

lenalidomide myeloma precursor condition publication bias smoldering myeloma systematic review

Journal

The oncologist
ISSN: 1549-490X
Titre abrégé: Oncologist
Pays: England
ID NLM: 9607837

Informations de publication

Date de publication:
05 Sep 2024
Historique:
received: 23 07 2024
accepted: 23 07 2024
medline: 5 9 2024
pubmed: 5 9 2024
entrez: 5 9 2024
Statut: aheadofprint

Résumé

Smoldering multiple myeloma (SMM), an asymptomatic precursor of multiple myeloma (MM), carries a variable risk of progression to MM. There is little consensus on the efficacy or optimal timing of treatment in SMM. We systematically reviewed the landscape of all clinical trials in SMM. We compared the efficacy of treatment regimens studied in SMM to results from these regimens when used in newly diagnosed multiple myeloma (NDMM), to determine whether the data suggest deeper responses in SMM versus NDMM. All prospective interventional clinical trials for SMM, including published studies, meeting abstracts, and unpublished trials listed on ClinicalTrials.gov up to April 1, 2023, were identified. Trial-related variables were captured, including treatment strategy and efficacy results. Relevant clinical endpoints were defined as overall survival (OS) and quality of life. Among 45 SMM trials identified, 38 (84.4%) assessed active myeloma drugs, while 7 (15.6%) studied bone-modifying agents alone. Of 18 randomized trials in SMM, only one (5.6%) had a primary endpoint of OS; the most common primary endpoint was progression-free survival (n = 7, 38.9%). Among 32 SMM trials with available results, 9 (28.1%) met their prespecified primary endpoint, of which 5 were single-arm studies. Six treatment regimens were tested in both SMM and NDMM; 5 regimens yielded a lower rate of very good partial response rate or better (≥VGPR) in SMM compared to the corresponding NDMM trial (32% vs 63%, 43% vs 53%, 40% vs 63%, 86% vs 89%, 92% vs 95%, and 94% vs 87%, respectively). In this systematic review of all prospective interventional clinical trials in SMM, we found significant variability in trial design, including randomization status, primary endpoints, and types of intervention used. Despite the statistical limitations, comparison of treatment regimens revealed no compelling evidence that the treatment is more effective when introduced early in SMM compared to NDMM.

Sections du résumé

BACKGROUND BACKGROUND
Smoldering multiple myeloma (SMM), an asymptomatic precursor of multiple myeloma (MM), carries a variable risk of progression to MM. There is little consensus on the efficacy or optimal timing of treatment in SMM. We systematically reviewed the landscape of all clinical trials in SMM. We compared the efficacy of treatment regimens studied in SMM to results from these regimens when used in newly diagnosed multiple myeloma (NDMM), to determine whether the data suggest deeper responses in SMM versus NDMM.
METHODS METHODS
All prospective interventional clinical trials for SMM, including published studies, meeting abstracts, and unpublished trials listed on ClinicalTrials.gov up to April 1, 2023, were identified. Trial-related variables were captured, including treatment strategy and efficacy results. Relevant clinical endpoints were defined as overall survival (OS) and quality of life.
RESULTS RESULTS
Among 45 SMM trials identified, 38 (84.4%) assessed active myeloma drugs, while 7 (15.6%) studied bone-modifying agents alone. Of 18 randomized trials in SMM, only one (5.6%) had a primary endpoint of OS; the most common primary endpoint was progression-free survival (n = 7, 38.9%). Among 32 SMM trials with available results, 9 (28.1%) met their prespecified primary endpoint, of which 5 were single-arm studies. Six treatment regimens were tested in both SMM and NDMM; 5 regimens yielded a lower rate of very good partial response rate or better (≥VGPR) in SMM compared to the corresponding NDMM trial (32% vs 63%, 43% vs 53%, 40% vs 63%, 86% vs 89%, 92% vs 95%, and 94% vs 87%, respectively).
CONCLUSION CONCLUSIONS
In this systematic review of all prospective interventional clinical trials in SMM, we found significant variability in trial design, including randomization status, primary endpoints, and types of intervention used. Despite the statistical limitations, comparison of treatment regimens revealed no compelling evidence that the treatment is more effective when introduced early in SMM compared to NDMM.

Identifiants

pubmed: 39236068
pii: 7749923
doi: 10.1093/oncolo/oyae219
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© The Author(s) 2024. Published by Oxford University Press.

Auteurs

Apoorva Kakkilaya (A)

John Sealy School of Medicine, University of Texas Medical Branch, Galveston, TX, United States.

Aaron Trando (A)

School of Medicine, University of California San Diego, La Jolla, CA, United States.

Edward R Scheffer Cliff (ERS)

Program on Regulation, Therapeutics and Law, Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.

Hira Mian (H)

Division of Hematology, McMaster University, Hamilton, Canada.

Samer Al Hadidi (S)

Myeloma Center, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR, United States.

Muhammad Aziz (M)

Division of Gastroenterology and Hepatology, University of Toledo, Toledo, OH, United States.

Aaron M Goodman (AM)

Division of Blood and Marrow Transplantation, University of California San Diego, La Jolla, CA, United States.

Ah-Reum Jeong (AR)

Division of Blood and Marrow Transplantation, University of California San Diego, La Jolla, CA, United States.

Wade L Smith (WL)

Mulford Health Science Library, University of Toledo, Toledo, OH, United States.

Amar H Kelkar (AH)

Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States.

David A Russler-Germain (DA)

Division of Oncology, Washington University School of Medicine, St. Louis, MO, United States.

Nikita Mehra (N)

Department of Medical Oncology, Cancer Institute (WIA), Chennai, India.

Rajshekhar Chakraborty (R)

Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, United States.

Morie A Gertz (MA)

Division of Hematology, Mayo Clinic, Rochester, MN, United States.

Ghulam Rehman Mohyuddin (GR)

Division of Hematology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, United States.

Classifications MeSH