Drug and Solute Transporters in Mediating Resistance to Novel Therapeutics in Multiple Myeloma

2021 ◽  
Author(s):  
Rachel L. Mynott ◽  
Craig T. Wallington-Beddoe
Keyword(s):  
Multiple Myeloma ◽  
Novel Therapeutics ◽  
Solute Transporters

Versikine, a proteolysis product of Versican: novel therapeutics for multiple myeloma

2016 ◽  
Vol 5 (S7) ◽  
pp. S1437-S1439
Author(s):  
Nidhi Gupta ◽  
Raman Kumar ◽  
Alpana Sharma
Keyword(s):  
Multiple Myeloma ◽  
Novel Therapeutics

scholarly journals Novel therapeutics in multiple myeloma

Hematology ◽  
2012 ◽  
Vol 17 (sup1) ◽  
pp. s105-s108 ◽  
Author(s):  
A Keith Stewart
Keyword(s):  
Multiple Myeloma ◽  
Novel Therapeutics

scholarly journals Introductory Chapter: Multiple Myeloma in the Era of Novel Therapeutics

2019 ◽  
Author(s):  
Khalid Ahmed Al-Anazi
Keyword(s):  
Multiple Myeloma ◽  
Novel Therapeutics

Survival Disparities Between African-American and Caucasian Patients with Multiple Myeloma Are Blunted in the Era of Novel Therapeutics and Autologous Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1395-1395 ◽  
Author(s):  
Nina Shah ◽  
Donna M Weber ◽  
Michael Wang ◽  
Sheeba Thomas ◽  
Jatin Shah ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
African American ◽  
Stem Cell ◽  
Median Overall Survival ◽  
Stage I ◽  
Single Center ◽  
Novel Therapeutics ◽  
Caucasian Patients

Abstract Abstract 1395 Poster Board I-417 Background: Multiple myeloma accounts for approximately 10% of hematologic malignancies diagnosed annually in the U.S. It is well documented that the African-American population is disproportionately affected by multiple myeloma in incidence and mortality. Survival data from the SEER database from 2001-2005 demonstrated higher mortality in African-American patients compared to Caucasian patients. However, more recent retrospective reviews in the era of autologous stem cell transplant (ASCT) did not support this finding. Thus the persistence of racial survival disparities in the era of ASCT and novel therapeutics is an evolving question. Methods: We performed a retrospective review of 170 African-American multiple myeloma patients and 170 age and gender-matched Caucasian patients initially seen at the M.D. Anderson Cancer Center from 1/1/2002 to 12/31/2008. Results: Three hundred forty previously untreated patients were analyzed. Median age at diagnosis was 57 years for both groups. For evaluable patients, the International Staging System at diagnosis was determined. The percentage of stage I, II and III patients in the African-American group was 53%, 28% and 19% respectively. The percentage of stage I, II and III patients in the Caucasian group was 40%, 30% and 29% respectively. These staging data were not significantly different between racial groups. In both groups, 89% of patients received a novel therapeutic (thalidomide, lenalidomide or bortezomib) during their treatment course. We found a statistically significant difference in the percentage of African-American and Caucasian patients who received high dose chemotherapy and ASCT (65% and 76%, respectively, p=0.04). There was no difference observed in the number of second transplants performed in the two groups (19 in both groups). Response to therapy is detailed in Table 1. There was no difference in overall response to any therapy of evaluable patients between the two groups. With a median follow-up time of 35 months, the median overall survival from diagnosis has not been reached in either group. Kaplan-Meir analysis shows that there is no difference in overall survival between black and white patients (p =0.1) Conclusions: In this single-center, retrospective study of multiple myeloma patients treated predominately with novel agents, with or without ASCT, no survival difference was observed between African-American and Caucasian patients. To our knowledge, this is the largest number of African-American myeloma patients analyzed for survival in a single-center study. Recognizing the potential disparities in healthcare access, this may not represent outcomes for all African-American patients with myeloma. Since median overall survival has not been reached in this data, it is possible that survival differences will become apparent in the future, and further follow-up is needed. However, this review suggests that in the era of novel therapeutics and ASCT resulting in improved overall response rates, survival in African-American patients may be equivalent to Caucasian patients. Further efforts are needed to enroll African-American patients on clinical trials to validate this observation prospectively. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Multiple Myeloma

Hematology ◽  
2002 ◽  
Vol 2002 (1) ◽  
pp. 214-240 ◽  
Author(s):  
Kenneth C. Anderson ◽  
John D. Shaughnessy ◽  
Bart Barlogie ◽  
Jean-Luc Harousseau ◽  
G. David Roodman
Keyword(s):  
Multiple Myeloma ◽  
Bone Disease ◽  
Plasma Cells ◽  
High Dose ◽  
Novel Therapeutics ◽  
Host Interaction ◽  
Adhesive Interactions ◽  
And Migration ◽  
Microarray Expression

Abstract This update provides new insights into the biology, diagnosis, prognosis, and treatment of multiple myeloma (MM) and its complications. In Section I, Drs. John Shaughnessy, Jr., and Bart Barlogie first correlate global gene microarray expression profiling of patient MM samples with normal plasma cells to provide the basis for a developmental stage-based classification of MM. The powerful clinical utility of these analyses is illustrated in delineating mechanism of drug action, identifying novel therapeutic targets, and providing a molecular analysis not only of the tumor cell, but also of the tumor microenvironment, in MM. In Section II, Dr. Jean-Luc Harousseau reviews the rationale and current results of high dose therapy and autologous stem cell transplantation in MM, including optimal patient selection, prognostic factors, conditioning regimens, sources of stem cells, use of tandem transplantation, and maintenance therapy. He then provides an update on the results of allotransplantation approaches in MM, focusing on proposed methods to reduce toxicity and exploit the graft-versus-MM alloimmune effect by transplantation earlier in the disease course, T cell depletion, and nonmyeloablative transplantation. In Section III, Dr. G. David Roodman provides recent insights into the mechanisms of osteoclast activation, interactions between bone and MM cells, adhesive interactions in MM bone disease, and osteoblast suppression. These recent advances not only provide insights into pathogenesis of MM bone disease, but also form the framework for novel therapeutics. In Section IV, Dr. Kenneth Anderson provides an up-to-date discussion of the role of the bone marrow microenvironment in promoting growth, survival, drug resistance, and migration of MM cells and the signaling cascades mediating these sequelae. These studies provide the framework for evaluation of novel therapeutics targeting the MM cell-host interaction in vivo in animal models and in derived clinical trials.

Persistent Racial/Ethnic Disparities in Outcomes for Multiple Myeloma: A SEER-Database Update

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1191-1191 ◽  
Author(s):  
Kevin R. Kelly ◽  
Dongyun Yang ◽  
Mayank Sharma ◽  
Vivek Roy ◽  
Asher A. Chanan-Khan ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Ethnic Minorities ◽  
Ethnic Disparities ◽  
Incidence Rates ◽  
Novel Agents ◽  
Age Group ◽  
Incremental Benefit ◽  
Novel Therapeutics ◽  
Race Ethnicity

Abstract Background: We have previously reported on ethnic disparities in outcomes of multiple myeloma (MM) pts (pts) and shown that Hispanics have the shortest median overall survival (OS) and myeloma-specific survival (MMS) while Asians have the longest. Ethnic minorities are increasing in number in the United States (US) and have been historically underrepresented in population databases with limited follow up since the introduction of novel agents for MM. We did an updated analysis with longer follow up for ethnic minorities to explore the changes in outcomes by race and also explored MM incidence rates, not reported previously. Methods: Surveillance Epidemiology and End Results (SEER) 13 Registry data (1973-2013) for adult pts (>18 yr) with confirmed diagnosis of MM was utilized. To avoid bias of under representation of ethnic minorities, analysis was restricted to pts diagnosed in 1992 or later. Years of diagnosis were 1992-1995 (pre-stem cell transplant; SCT), 1996-2002 (after SCT but before novel therapeutics) and 2003-2013 (after introduction of novel therapeutics). Cases that received a diagnosis at death certificate/autopsy, without follow-up records, lacking documentation on age at diagnosis, sex, or race/ethnicity were excluded. Cox proportional hazards models were used to evaluate association between patient characteristics and survival. All statistical tests utilized the SAS software (v9.4) and were two-sided with a significance level of 0.05. Results: The final analysis included 68431 MM pts (37300 males; 55%, 31131 females; 45%). Age-group cohorts included: 18-44 yr (2519; 4%), 45-54 yr (8131; 12%), 55-64 yr (15416; 23%), 65-74 yr (20214; 30%), and ≥75 yr (22151; 32%). Mutually exclusive racial subgroups included: non-Hispanic White (NHW; 44618, 65%), non-Hispanic African-American (AA; 13164, 19%), non-Hispanic Asian/Pacific Islanders (API; 3570, 5%), Hispanic (H; 6759, 10%) and Native American (NA; 320, 0.5%). Trends in age-specific incidence rates were similar for all races but except the 20-24 yr group, were highest for AA and lowest for API. (Figure 1) Survival analysis showed that females had a better median OS (3.4 vs 3 yr; p<0.001) and MMS (4.7 vs 4.4 yr; p<0.001) than males. Age was an independent predictor of OS (p<0.001) with the median OS changing from 7.3 yr in 18-44 to 1.9 yr in ≥75 age group. Similar results were seen for age groups and MMS as well (p<0.001). During the three pre-specified time periods for year of diagnosis, both the median OS and MMS progressively improved (P<0.001) suggesting improved outcomes secondary to treatment advancements. H and AA had the worst median OS (3.1 yr) as compared to NHW and API (3.3 yr) (p<0.001) and H had the worst median MMS (4.3 yr) while API had the best (5.1 yr) (p<0.001). Survival analyses were performed for ≥75 age group separately since it was the largest and traditionally with worst outcomes. The difference in median OS by gender was still significant (p<0.001) but less pronounced (1.8 vs 1.9 yr) and was not significant for MMS (p=0.33). Due to less SCT utilization, no incremental OS or MMS benefit was seen prior to advent of novel agents but since 2003 the ≥75 group did have a small benefit for OS (2 vs 1.6 yr, p<0.001) and MMS (3 vs 2.3 yr, p<0.001). Race no longer predicted for a statistically significant OS difference (p=0.52) while for MMS, H continued to have the worst (2.5 yr) and NA the best (3.8 yr) outcome (p<0.001). 5-year relative survival rates (RSR) over time showed an incremental improvement in recent years for all racial groups except API ≥70 yr (Figure 2) with generally an increased incremental benefit for the <70 yr age group than the elderly. For majority of races no incremental benefit was seen in 5-yr RSR for ≥70 yr pts between 1992-1995 and 1996-2003 but improvement was seen in 2004-2013. Conclusions: In a fast changing US demographic mix, significant disparities for MM incidence and outcomes exist by race/ethnicity. As compared to our previous analyses, new trends have emerged with Whites having an improved median OS than AA while H continue to have the worst MMS and API the best. Differences in median OS among races are no longer significant in elderly pts. A modest benefit in OS is being seen for elderly pts since the advent of novel therapeutics. Studies of ethnic disparities are important for evaluating management needs of specific patient populations as well as optimal triaging of healthcare resources. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Kelly: Novartis: Consultancy, Speakers Bureau; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Speakers Bureau. Ailawadhi:Pharmacyclics: Consultancy; Novartis: Consultancy; Amgen Inc: Consultancy; Takeda Oncology: Consultancy.

scholarly journals A clinical update on the role of carfilzomib in the treatment of relapsed or refractory multiple myeloma

2016 ◽  
Vol 7 (6) ◽  
pp. 330-344 ◽  
Author(s):  
B. Franken ◽  
N.W.C.J. van de Donk ◽  
J.C. Cloos ◽  
S. Zweegman ◽  
H.M. Lokhorst
Keyword(s):  
Multiple Myeloma ◽  
Hdac Inhibitors ◽  
The United States ◽  
Phase Iii ◽  
Negative Effects ◽  
Refractory Multiple Myeloma ◽  
Novel Therapeutics ◽  
Treatment Regimens ◽  
Optimal Dosing

Even though the prognosis of patients with multiple myeloma is continuing to improve, all patients eventually develop relapsed refractory disease. Several novel therapeutics have been developed in the last few years including the second-generation proteasome inhibitor carfilzomib which has been approved for patients with relapsed and refractory multiple myeloma in the United States since 2012. Recently data from several phase III studies have become available showing the promising efficacy of carfilzomib in combination with lenalidomide, which led to the renewed approval of carfilzomib in combination with lenalidomide and dexamethasone for relapsed myeloma in 2015. Furthermore carfilzomib showed superiority over bortezomib on both efficacy and toxicity profiles, especially a profoundly lower incidence in polyneuropathy. Carfilzomib has been shown to partially overcome the negative effects of high-risk cytogenetics. Promising combinations of carfilzomib with histone deacetylase (HDAC) inhibitors, pomalidomide and several other novel therapeutics have been presented in early studies. The optimal dosing regimen and sequence of treatment regimens remain important questions for the future.

scholarly journals Patterns of second primary malignancy risk in multiple myeloma patients before and after the introduction of novel therapeutics

2013 ◽  
Vol 3 (6) ◽  
pp. e121-e121 ◽  
Author(s):  
P Razavi ◽  
K A Rand ◽  
W Cozen ◽  
A Chanan-Khan ◽  
S Usmani ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Second Primary ◽  
Second Primary Malignancy ◽  
Primary Malignancy ◽  
Novel Therapeutics ◽  
Malignancy Risk ◽  
Before And After

scholarly journals Synopsis of a Roundtable on Validating Novel Therapeutics for Multiple Myeloma

2006 ◽  
Vol 12 (22) ◽  
pp. 6603-6610 ◽  
Author(s):  
William Dalton ◽  
Kenneth C. Anderson
Keyword(s):  
Multiple Myeloma ◽  
Novel Therapeutics
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