Treatment Options for Patients With Heavily Pretreated Relapsed and Refractory Multiple Myeloma

Dimopoulos, Meletios Α.; Richardson, Paul G.; Lonial, Sagar

doi:10.1016/j.clml.2022.01.011

Cited by 22 publications

(11 citation statements)

References 94 publications

(68 reference statements)

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“…The main side effects include myelosuppression, fatigue and diarrhea [ 4 ]. Pomalidomide can be administered with dexamethasone or in combination with proteasome inhibitors (bortezomib) and monoclonal antibodies (isatuximab, daratumumab) [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Pomalidomide Treatment in Relapsed/Refractory Multiple Myeloma Patients—Real-World Data From Hungary

Lovas¹,

Al-Ali²,

Varga³

et al. 2022

Pathol. Oncol. Res.

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Pomalidomide is a third generation immunomodulatory drug in the treatment of refractory and relapsed multiple myeloma patients. Our aim was to investigate the efficacy and safety of pomalidomide therapy in a real world setting. Eighty-six Hungarian patients were included, 45 of whom received pomalidomide ± an alkylating agent, while in 38 of them pomalidomide was combined with a proteasome inhibitor. 56 patients (65%) showed any response to the treatment with 18 complete or very good partial remissions and 38 partial remissions. At a median duration of follow-up of 18.6 months, the median progression-free survival (PFS) was 9.03 months, while the median overall survival (OS) was 16.53 months in the whole cohort. Patients with early stage disease (R-ISS 1 and 2) had better survival results than those with stage 3 myeloma (p = 0.002). Neither the number of prior treatment lines, nor lenalidomide refractoriness had a significant impact on PFS. PFS was found similar between the cohort of patients with impaired renal function and the cohort without kidney involvement. During the study, eight mortal infections and two fatal bleeding complications occurred, however, mild hematologic and gastrointestinal toxicities were identified as the most frequent adverse events. The results of our investigations confirm that pomalidomide is an effective treatment option for relapsed/refractory MM, besides, the safety profile is satisfactory in subjects with both normal and impaired renal function.

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Section: Introductionmentioning

confidence: 99%

Pomalidomide Treatment in Relapsed/Refractory Multiple Myeloma Patients—Real-World Data From Hungary

Lovas¹,

Al-Ali²,

Varga³

et al. 2022

Pathol. Oncol. Res.

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“…The immunomodulatory effects of anti-CD38 mAbs promote T-cell proliferation and effector function through inhibition of CD38 enzymatic activity, which reduces adenosine immunosuppressive activity and elimination of CD38 + immunosuppressive cells [14]. mAbs targeting other myeloma cell epitopes have also been developed [15,16]. Elotuzumab, a humanized IgG1 mAb targeting the SLAMF7 protein that is expressed on myeloma cells independent of cytogenetic abnormalities, mediates myeloma cell killing through mechanisms similar to those of the aforementioned anti-CD38 mAbs [15,16].…”

Section: Current Landscape Of Immune-based Drugs In the Early-line Tr...mentioning

confidence: 99%

“…mAbs targeting other myeloma cell epitopes have also been developed [15,16]. Elotuzumab, a humanized IgG1 mAb targeting the SLAMF7 protein that is expressed on myeloma cells independent of cytogenetic abnormalities, mediates myeloma cell killing through mechanisms similar to those of the aforementioned anti-CD38 mAbs [15,16]. Additional drugs considered within combination regimens are alkylating agents (e.g., cyclophosphamide), which cause DNA damage, and panobinostat, an inhibitor of the enzyme histone deacetylase, which activates the expression of tumor suppressor genes through the opening of chromatin structures initially silenced through histone acetylation [17].…”

Section: Current Landscape Of Immune-based Drugs In the Early-line Tr...mentioning

confidence: 99%

“…Another option in this setting is the combination of selinexor with bortezomib-dexamethasone, as evaluated in the phase 3 BOSTON trial [43]. Pomalidomide has also been shown to inhibit the proliferation of lenalidomideresistant MM cell lines [16]. This observed in vitro efficacy is supported by the results of the phase 3 OPTIMISMM trial, which found that treatment with pomalidomide, bortezomib, and lowdose dexamethasone improved PFS compared with bortezomib and low-dose dexamethasone in patients with RRMM and lenalidomiderefractory disease (median PFS, 9.5 vs 5.6 months, respectively) [44,45].…”

Section: Current Landscape Of Immune-based Drugs In the Early-line Tr...mentioning

confidence: 99%

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Clinical evidence for immune-based strategies in early-line multiple myeloma: current challenges in decision-making for subsequent therapy

et al. 2023

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Almost all patients with multiple myeloma (MM) will eventually develop disease that has relapsed with or become refractory to available treatments and will require additional therapy. However, data are still lacking on how best to sequence regimens in the relapsed/refractory (RR) setting after the failure of early-line lenalidomide, bortezomib, and/or daratumumab, the most commonly used agents in clinical practice today. With the treatment landscape rapidly changing in response to emerging clinical trial data and approvals of several new drugs and additional combinations, it is critically important to focus on patients with RRMM. Variability in patient baseline characteristics, such as the number of prior lines of treatment, refractoriness to prior treatments, prior stem cell transplant, and timing and dosing of prior lenalidomide, makes it difficult to select the best options for patients with RRMM for whom first-line treatments have failed. The aim of this review is to provide both an overview of current therapies and future directions within the RRMM treatment landscape, and a framework for clinicians to choose the most promising next treatment option.

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“…This has led to the rapid development and clinical introduction of many novel molecular-targeted therapies, including proteasome inhibitors (PI), immunomodulatory drugs, and immunotherapies, which have dramatically improved the prognosis of patients with MM [ 5 ]. However, relapse is highly likely in almost all MM patients; thus, there is an urgent need to develop next-generation therapeutic agents that could cure MM [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Targeting CAM-DR and Mitochondrial Transfer for the Treatment of Multiple Myeloma

et al. 2022

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The prognosis of patients with multiple myeloma (MM) has improved dramatically with the introduction of new therapeutic drugs, but the disease eventually becomes drug-resistant, following an intractable and incurable course. A myeloma niche (MM niche) develops in the bone marrow microenvironment and plays an important role in the drug resistance mechanism of MM. In particular, adhesion between MM cells and bone marrow stromal cells mediated by adhesion molecules induces cell adhesion-mediated drug resistance (CAM-DR). Analyses of the role of mitochondria in cancer cells, including MM cells, has revealed that the mechanism leading to drug resistance involves exchange of mitochondria between cells (mitochondrial transfer) via tunneling nanotubes (TNTs) within the MM niche. Here, we describe the discovery of these drug resistance mechanisms and the identification of promising therapeutic agents primarily targeting CAM-DR, mitochondrial transfer, and TNTs.

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Treatment Options for Patients With Heavily Pretreated Relapsed and Refractory Multiple Myeloma

Cited by 22 publications

References 94 publications

Pomalidomide Treatment in Relapsed/Refractory Multiple Myeloma Patients—Real-World Data From Hungary

Pomalidomide Treatment in Relapsed/Refractory Multiple Myeloma Patients—Real-World Data From Hungary

Clinical evidence for immune-based strategies in early-line multiple myeloma: current challenges in decision-making for subsequent therapy

Targeting CAM-DR and Mitochondrial Transfer for the Treatment of Multiple Myeloma

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