Cited by 19Multiple Myeloma Research and TreatmentsChronic Lymphocytic Leukemia ResearchLymphoma Diagnosis and Treatment

Revisiting the role of alkylating agents in multiple myeloma: Up-to-date evidence and future perspectives

Costa, Bruno Almeida, Mouhieddine, Tarek H., Ortiz, Ricardo J., Richter, Joshua·2023·Critical Reviews in Oncology/Hematology

Abstract

From the 1960s to the early 2000s, alkylating agents (e.g., melphalan, cyclophosphamide, and bendamustine) remained a key component of standard therapy for newly-diagnosed or relapsed/refractory multiple myeloma (MM). Later on, their associated toxicities (including second primary malignancies) and the unprecedented efficacy of novel therapies have led clinicians to increasingly consider alkylator-free approaches. Meanwhile, new alkylating agents (e.g., melflufen) and new applications of old alkylators (e.g., lymphodepletion before chimeric antigen receptor T-cell [CAR-T] therapy) have emerged in recent years. Given the expanding use of antigen-directed modalities (e.g., monoclonal antibodies, bispecific antibodies, and CAR-T therapy), this review explores the current and future role of alkylating agents in different treatment settings (e.g., induction, consolidation, stem cell mobilization, pre-transplant conditioning, salvage, bridging, and lymphodepleting chemotherapy) to ellucidate the role of alkylator-based regimens in modern-day MM management.

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Crossref · 10.1016/j.critrevonc.2023.104040

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  • Several non-targeted drugs have been approved for MM treatment, including alkylating agents, corticosteroids, immunomodulatory imide drugs, proteasome inhibitors, histone deacetylase inhibitors, and XPO1 inhibitor.

    “Over the past few decades, several non-targeted drugs have been approved for the treatment of multiple myeloma, including alkylating agents [40], corticosteroids [41–43], immunomodulatory imide drugs (IMiDs) [44–47], proteasome inhibitors (PIs) [42, 48–51], histone deacetylases (iHDACs) inhibitors [37, 52, 53], and XPO1 inhibitor [54–56] (Table 1).”

    From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [40]

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Authors
Costa, B. A., Mouhieddine, T. H., Ortiz, R. J., & Richter, J.
Affiliations
  • Icahn School of Medicine at Mount Sinai (US)
  • Tisch Cancer Institute (US)
Corresponding author
Richter, Joshua
Venue
Critical Reviews in Oncology/Hematology
Publisher
Elsevier BV
Published
2023-07
Volume
187
Pages
104040
ISSN
1040-8428 (ISSN-L)
OpenAlex
W4378212210
Cited by
18
References
256
Citations by year
2026: 3 · 2025: 8 · 2024: 6 · 2023: 1
FWCI
0.92
Type
journal article
Language
en
Open access
closed
Locations
  • Critical Reviews in Oncology/Hematology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
  • Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
Keywords
alkylating agents, multiple myeloma, melphalan, cyclophosphamide, bendamustine, melflufen, lymphocyte depletion, CAR T-cell therapy, second primary malignancy, relapsed/refractory multiple myeloma, stem cell mobilization, pre-transplant conditioning, consolidation therapy, bridging therapy
MeSH terms
Bendamustine Hydrochloride, Receptors, Chimeric Antigen, Alkylating Agents, Cyclophosphamide, Humans, Multiple Myeloma

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