Daratumumab, pomalidomide and dexamethasone combination therapy in daratumumab and/or pomalidomide refractory multiple myeloma

Hussain, Mohammed J; Robinson, Myra; Hamadeh, Issam; Arnall, Justin; Bhutani, Manisha; Atrash, Shebli; Friend, Reed; Pineda‐Roman, Mauricio; Symanowski, James T.; Usmani, Saad Z.; Voorhees, Peter M.

doi:10.1111/bjh.15716

Cited by 13 publications

(14 citation statements)

References 11 publications

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“…The strong affinity for daratumumab to a unique epitope on myeloma plasma cells activates efficient complement-dependent cytotoxicity as one of its main mechanisms of action. Among patients with relapsed/refractory MM, daratumumab has demonstrated efficacy as monotherapy (Lokhorst et al, 2015;Lonial et al, 2016) and in combinations with lenalidomide, pomalidomide and bortezomib (Dimopoulos et al, 2016;Palumbo et al, 2016;Hussain et al, 2018). Based on these studies, daratumumab monotherapy and combinations are FDA-approved in RRMM.…”

Section: Resultsmentioning

confidence: 99%

Daratumumab in high‐risk relapsed/refractory multiple myeloma patients: adverse effect of chromosome 1q21 gain/amplification and GEP70 status on outcome

et al. 2019

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Summary Gain of chromosome 1q21 and the gene expression‐based GEP70 risk score are established prognostic markers for newly diagnosed Multiple Myeloma (MM) patients. Here we addressed the prognostic impact of these two markers in 81 relapsed/refractory (RR) MM patients treated with the CD38‐antibody daratumumab. Fluorescence in situ hybridization for 1q21 was performed at initial presentation, while the GEP70 score was determined at initial presentation and prior to daratumumab treatment. While the GEP70 at initial presentation showed a trend for inferior survival, the GEP70 collected prior to daratumumab treatment was significantly associated with poor outcome (P < 0·05). The worst outcome was seen for patients who were positive for gain(1q) and classified as GEP70 high risk prior to daratumumab [progression‐free (PFS) and overall survival (OS) of 0·3 years (95% CI: 0·15–1·4 years) and 0·8 years (95% CI: 0·5–1·9 years) respectively], while the median PFS and OS were not reached by patients without gain(1q) and GEP70 low‐risk status. In conclusion, gain(1q) and the GEP70 are powerful prognostic markers for RR MM patients treated with daratumumab, and patients classified as high risk according to these markers experience shorter treatment response.

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Section: Resultsmentioning

confidence: 99%

Daratumumab in high‐risk relapsed/refractory multiple myeloma patients: adverse effect of chromosome 1q21 gain/amplification and GEP70 status on outcome

et al. 2019

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“…This study showed that a combination of daratumumab and pomalidomide helps overcome resistance in some cases. But this is a retrospective cohort study with a limited population, needs a randomized controlled trial to confirm the association that has been shown in this study [ 27 ]. Siegel et al in their clinical trial mainly focused on patients who are refractory or relapsed with lenalidomide.…”

Section: Reviewmentioning

confidence: 78%

Role of Daratumumab in Combination With Standard Therapies in Patients With Relapsed and Refractory Multiple Myeloma

Bapatla

Kaul

Dhalla

et al. 2021

Cureus

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Multiple myeloma (MM) is a hematological malignancy characterized by renal insufficiency, bone lesions, anemia, and hypercalcemia. In this modern era of medicine, even with the development of drugs like immunomodulatory agents (IMiDs) and proteasome inhibitors (PI), the treatment of MM prevails as a challenge. However, even after the attainment of total remission, relapse of MM and disease progression is frequent. That is why there is an urgent requirement to develop novel monoclonal antibody drugs. The latest drugs for the treatment of relapsed and refractory MM (RRMM) approved by the Food and Drug Administration (FDA) are elotuzumab and daratumumab. In this article, we will discuss daratumumab with different combination therapies. The literature exploration was done using PubMed, Medline, PubMed Central, and Research Gate. Keywords used to search are monoclonal antibodies, daratumumab, RRMM, and novel agents. Our review article, which includes 21 relevant articles, demonstrated that daratumumab in different combinations showed significant progression-free survival (PFS) without severe safety concerns. However, while observing all the studies, neither of them studied the combination therapies of daratumumab in end-stage renal disease (ESRD) patients. Hence, more randomized controlled clinical trials should be done to understand and compare the effect of the combination of daratumumab with the standard of care therapies in ESRD patients.

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“…As for other IMIDs, the association of pomalidomide with other classes of anti-MM drugs has been shown promising results [ 237 , 238 , 239 , 240 , 241 , 242 , 243 , 244 ].…”

Section: Vegf/vegfr Inhibition In MMmentioning

confidence: 99%

Anti-VEGF Drugs in the Treatment of Multiple Myeloma Patients

Ria

Melaccio

Racanelli

et al. 2020

JCM

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The interaction between the bone marrow microenvironment and plasma cells plays an essential role in multiple myeloma progression and drug resistance. The vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) pathway in vascular endothelial cells activates and promotes angiogenesis. Moreover, VEGF activates and promotes vasculogenesis and vasculogenic mimicry when it interacts with VEGF receptors expressed in precursor cells and inflammatory cells, respectively. In myeloma bone marrow, VEGF and VEGF receptor expression are upregulated and hyperactive in the stromal and tumor cells. It has been demonstrated that several antiangiogenic agents can effectively target VEGF-related pathways in the preclinical phase. However, they are not successful in treating multiple myeloma, probably due to the vicarious action of other cytokines and signaling pathways. Thus, the simultaneous blocking of multiple cytokine pathways, including the VEGF/VEGFR pathway, may represent a valid strategy to treat multiple myeloma. This review aims to summarize recent advances in understanding the role of the VEGF/VEGFR pathway in multiple myeloma, and mainly focuses on the transcription pathway and on strategies that target this pathway.

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Daratumumab, pomalidomide and dexamethasone combination therapy in daratumumab and/or pomalidomide refractory multiple myeloma

Cited by 13 publications

References 11 publications

Daratumumab in high‐risk relapsed/refractory multiple myeloma patients: adverse effect of chromosome 1q21 gain/amplification and GEP70 status on outcome

Daratumumab in high‐risk relapsed/refractory multiple myeloma patients: adverse effect of chromosome 1q21 gain/amplification and GEP70 status on outcome

Role of Daratumumab in Combination With Standard Therapies in Patients With Relapsed and Refractory Multiple Myeloma

Anti-VEGF Drugs in the Treatment of Multiple Myeloma Patients

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