scholarly journals An update on the role of daratumumab in the treatment of multiple myeloma

2016 ◽  
Vol 8 (1) ◽  
pp. 28-37 ◽  
Author(s):  
Caitlin Costello
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Blood Compatibility ◽  
Daily Practice ◽  
Combination Strategies ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Phase Ii And Iii ◽  
Future Plans

Monoclonal antibodies (mAbs) have emerged as a promising new drug class for the treatment of multiple myeloma (MM). Daratumumab (DARA), a CD38 mAb, has demonstrated safety, tolerability and activity in a range of clinical trials, both as monotherapy and in combination strategies for MM. The favorable efficacy results in heavily pretreated patients with advanced MM have provided the rationale for the investigation of DARA in a number of ongoing and future phase II and III trials. The general tolerability of mAbs has allowed for widespread investigation and use of DARA among a variety of MM patients, however their use requires special consideration. Infusion-related reactions (IRRs), interference with blood compatibility assays and response assessments are all unique factors related to the use of DARA. This review provides an update of the results from the DARA clinical trials conducted to date, its future plans for investigation, and practical management considerations for the use of DARA in daily practice.

Efficacy of daratumumab monotherapy in real-world heavily pretreated patients with relapsed or refractory multiple myeloma

2019 ◽  
Vol 64 (2) ◽  
pp. 349-355 ◽  
Author(s):  
Aleksander Salomon-Perzyński ◽  
Adam Walter-Croneck ◽  
Lidia Usnarska-Zubkiewicz ◽  
Dominik Dytfeld ◽  
Patrycja Zielińska ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Real World ◽  
Refractory Multiple Myeloma ◽  
Heavily Pretreated ◽  
Pretreated Patients

scholarly journals Sequencing multiple myeloma therapies with and after antibody therapies

Hematology ◽  
2020 ◽  
Vol 2020 (1) ◽  
pp. 248-258
Author(s):  
Niels W. C. J. van de Donk
Keyword(s):  
Multiple Myeloma ◽  
Proteasome Inhibitors ◽  
Related Factors ◽  
Prior Therapy ◽  
Choice Of Treatment ◽  
Heavily Pretreated ◽  
First Relapse ◽  
Pretreated Patients ◽  
New Treatment ◽  
Selection Of

Abstract In multiple myeloma (MM), treatment selection and sequencing become increasingly complex with the increasing number of therapeutic options, including antibodies. Choice of treatment is dependent on various factors including patient- and tumor-related features. In addition, treatment-related factors, such as type and response to prior therapy, are also critical in terms of the selection of a new treatment regimen. Furthermore, approval status and reimbursement policies influence treatment choice. At the time of first relapse, patients who received a bortezomib-based regimen can switch to lenalidomide-based treatment, whereas patients who received lenalidomide until progression can switch to a proteasome inhibitor–based therapy. Alternatively, there is increasing evidence that pomalidomide-based triplets are also effective following the development of lenalidomide-refractory disease both in early and later relapse settings. Patients who become refractory to immunomodulatory drugs, proteasome inhibitors, and CD38 antibodies have a poor prognosis. These triple-class refractory patients may benefit from novel, recently approved agents such as XPO1 inhibitors or from participation in a clinical trial. Furthermore, retreatment with agents that were received in previous lines of therapy can also be considered in heavily pretreated patients, for example, in combination with classic cytotoxic drugs. Importantly, with the increasing use of CD38 antibodies in newly diagnosed and early relapsed/refractory MM, more information is needed on the potential value of retreatment with CD38 antibodies. With the introduction of new immunotherapies with novel modes of action, we also need a better understanding of sequencing of immunotherapeutic agents by taking into account the effect of prior therapy on immune function.

scholarly journals Disease and outcome disparities in multiple myeloma: exploring the role of race/ethnicity in the Cooperative Group clinical trials

2018 ◽  
Vol 8 (7) ◽  
Author(s):  
Sikander Ailawadhi ◽  
Susanna Jacobus ◽  
Rachael Sexton ◽  
Alexander K. Stewart ◽  
Angela Dispenzieri ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Cooperative Group ◽  
Race Ethnicity

scholarly journals Carfilzomib Based Treatment Strategies in the Management of Relapsed/Refractory Multiple Myeloma with Extramedullary Disease

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1035 ◽  
Author(s):  
Xiang Zhou ◽  
Patricia Flüchter ◽  
Katharina Nickel ◽  
Katharina Meckel ◽  
Janin Messerschmidt ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Response Rate ◽  
Treatment Strategies ◽  
Progression Free Survival ◽  
Serological Response ◽  
Free Survival ◽  
Refractory Multiple Myeloma ◽  
Extramedullary Disease ◽  
Heavily Pretreated ◽  
Pretreated Patients

Published experience with carfilzomib in patients with relapsed/refractory multiple myeloma (RRMM) and extramedullary disease (EMD) is still limited. The current study aimed to assess the efficacy and safety of carfilzomib containing therapy regimens in EMD. We retrospectively analyzed 45 patients with extramedullary RRMM treated with carfilzomib from June 2013 to September 2019. The median age at the start of carfilzomib was 64 (range 40–80) years. Twenty (44%) and 25 (56%) patients had paraosseous manifestation and EMD without adjacency to bone, respectively. The serological overall response rate (ORR) was 59%. Extramedullary response was evaluable in 33 patients, nine (27%) of them achieved partial remission (PR) (ORR = 27%). In 15 (33%) patients, we observed no extramedullary response despite serological response. The median progression-free survival (PFS) and overall survival (OS) were five (95% CI, 3.5–6.5) and ten (95% CI, 7.5–12.5) months, respectively. EMD without adjacency to bone was associated with a significantly inferior PFS (p = 0.004) and OS (p = 0.04) compared to paraosseous lesions. Carfilzomib based treatment strategies showed some efficacy in heavily pretreated patients with extramedullary RRMM but could not overcome the negative prognostic value of EMD. Due to the discrepancy between serological and extramedullary response, evaluation of extramedullary response using imaging is mandatory in these patients.

Impact of metformin on outcomes in patients (pts) with metastatic renal cell carcinoma (mRCC): Results from a pooled clinical trials database.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 531-531
Author(s):  
Lana Hamieh ◽  
Rana R. McKay ◽  
Suzanne S Mickey ◽  
Xun Lin ◽  
Ronit Simantov ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cox Regression ◽  
Mapk Pathway ◽  
Risk Groups ◽  
Diabetic Patients ◽  
First Line Therapy ◽  
Kaplan Meier ◽  
Tumor Types ◽  
Phase Ii And Iii

531 Background: Metformin has been shown to confer anti-neoplastic properties in several tumor types. Its effect on outcomes in mRCC patients has not been completely characterized. In this study, we evaluated the role of metformin on survival outcomes in pts with mRCC. Methods: We conducted a retrospective study of pts with mRCC treated on several phase II and III clinical trials from 2003-2013. We analyzed overall survival (OS) in the metformin users versus non-users using the Cox regression model and the Kaplan-Meier method. Results: We identified 4,736 pts with mRCC including 486 diabetic pts of whom 218 (4.6%) were metformin users. The majority were <65 years of age (69%), male (71%), with clear-cell histology (89%) and prior nephrectomy (70%). With regard to IMDC risk groups, 14%, 42%, and 24% had favorable, intermediate, and poor-risk disease, respectively. Pts received treatment with sunitinib (n=1,059), sorafenib (n=772), axitinib (n=896), temsirolimus (TEM) (n=457), TEM + interferon (IFN)-α (n=208), bevacizumab (BEV) + TEM (n=393), BEV + IFN-α (n=391), or IFN-α (n=560); overall 3,044 (64%) received first-line therapy. In the total cohort, metformin use did not impact OS when compared to users of other anti-diabetic agents (p=0.17) or non-diabetics (p=0.69). In diabetic pts, metformin use did not confer a survival advantage when stratified by type of therapy and IMDC risk group. However, in the cohort of diabetic pts receiving sunitinib (n=128), metformin use was associated with an improvement in OS when compared to users of non-metformin anti-diabetic agents (29.3 versus 20.9 months, respectively, p=0.0008, HR 0.051, 95% CI 0.009, 0.292). Conclusions: This is the largest study to date investigating the role of metformin on outcomes in mRCC pts. In this analysis, we demonstrate that concomitant use of metformin may improve survival in diabetic pts with mRCC treated with sunitinib. Based on preclinical data, we hypothesize that the mechanism underlying this survival benefit may be related to synergistic inhibition of the MAPK pathway. However, the study is limited by the small number of diabetic patients. Larger prospective studies are warranted to validate these results.

scholarly journals Daratumumab in untreated newly diagnosed multiple myeloma

2019 ◽  
Vol 10 ◽  
pp. 204062071989487 ◽  
Author(s):  
Nadine Abdallah ◽  
Shaji K. Kumar
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibody ◽  
Clinical Trials ◽  
High Risk ◽  
Human Monoclonal Antibody ◽  
Proteasome Inhibitors ◽  
Immunomodulatory Drugs ◽  
Newly Diagnosed ◽  
Infusion Reactions

The treatment of multiple myeloma has evolved markedly in the last decade, but mortality remains high, emphasizing the need for more effective therapies. Daratumumab, a fully human monoclonal antibody targeting CD38, has shown clinical efficacy in relapsed/refractory multiple myeloma both as monotherapy and in combination with other drugs, including novel agents. More recently, promising results have been reported in patients with untreated newly diagnosed multiple myeloma (NDMM). Clinical trials thus far have shown enhanced efficacy and tolerability of several daratumumab-based combinations in both transplant ineligible and eligible patients, without compromising transplant ability. However, benefit in high-risk subpopulations is still unclear. A subcutaneous formulation of daratumumab has been introduced to decrease the risk of infusion reactions, with preliminary results showing non-inferior efficacy. The antimyeloma activity of daratumumab is achieved through multiple mechanisms including direct, Fc-dependent, and immunomodulatory mechanisms. Enhanced efficacy of daratumumab in combination with immunomodulatory drugs and proteasome inhibitors is supported by preclinical data showing synergism. This review will focus on the role of daratumumab in untreated NDMM patients, highlighting the results of major clinical trials, and listing ongoing trials that are evaluating various daratumumab-based combinations in this setting.

scholarly journals Immunotherapy in Multiple Myeloma—Time for a Second Major Paradigm Shift

2021 ◽  
pp. OP.21.00032
Author(s):  
Meera Mohan ◽  
Parameswaran Hari ◽  
Binod Dhakal
Keyword(s):  
Multiple Myeloma ◽  
Paradigm Shift ◽  
Hematologic Malignancies ◽  
Cell Therapies ◽  
Immune Therapies ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Major Transformation ◽  
Immunologic Approach

Multiple myeloma (MM) is a genetically heterogenous disease and remains mostly incurable with a small group of patients achieving long-term disease remission. The past decade witnessed enormous efforts to break the circulus vitiosus of tumor-induced immunosuppression and to re-engage the immune system to fight cancer. The first-in-class anti-CD38 monoclonal antibody, daratumumab, has shown unprecedented responses especially in combination with other novel agents in both newly diagnosed and relapsed MM. There has been great interest in harnessing the power of T cells with bispecific antibodies and chimeric antigen receptor T-cell therapies in hematologic malignancies including MM. These immune-based approaches have shown notable antimyeloma effects with deeper, durable responses in early clinical trials of heavily pretreated patients with MM with limited therapeutic options. Several trials are underway investigating both single and combinatorial immune therapies at different stages with a hope to bring major transformation in MM. In the current review, we summarize how an immunologic approach offers promise for the treatment of MM and is setting the stage for second major paradigm shift 2 decades after the emergence of thalidomide and novel therapeutics.

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