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Background:It has been well documented that each additional line of treatment is associated with lower rates of deeper responses, shorter duration of treatment, and increased rates of toxicities/comorbidities in patients with multiple myeloma (MM; Yong K, et al. Br J Haematol 2016. 175[2]:252–264). These factors contribute to treatment discontinuation and impact the proportion of patients reaching subsequent lines of therapy.Aims:To characterize the rate of therapy attrition at relapse for patients with newly diagnosed MM (NDMM) who are transplant eligible in the United States.Methods:Patients with NDMM were identified from 3 US patient‐level data sources: the OPTUM™ Commercial Claims database (period: January 2000–March 2017), the OPTUM™ Electronic Medical Records (EMR) database (period: January 2007–March 2016), and the Surveillance, Epidemiology, and End Results (SEER)‐Medicare Linked database (period: January 2007–December 2014). Patients had 1) an index MM diagnosis on or after 1 January 2007, 2) medical prescription coverage in place at diagnosis, 3) no prior malignancies in the one‐year period prior to index diagnosis, 4) a one‐year look‐back period prior to index diagnosis, and 5) received ≥1 lines of therapy. Patients were considered transplant eligible if they received stem cell transplantation anytime during the follow‐up period. Baseline characteristics including comorbidities, index age, frontline treatment regimens and attrition rates at each subsequent line of therapy were characterized. Attrition was defined as the percentage of patients who did not have any recorded subsequent MM treatments as a result of death or lost to follow‐up in the database for any reason, including end of the database.Results:A total of 1,599 patients were included in this analysis. Baseline patient characteristics and pre‐existing comorbidities are summarized in Table 1. The induction regimens used as frontline treatments included bortezomib/dexamethasone (22%), lenalidomide/dexamethasone (13%), bortezomib/lenalidomide/dexamethasone (25%), all other bortezomib combinations (20%), and other (20%). The proportions of patients observed to progress to each subsequent line of therapy are summarized in Table 2. In total, 77% of patients received a second line of therapy, and only 55% received a third line treatment. The proportion of patients not receiving a subsequent line of therapy due to death is also summarized by lines of therapy in Table 2.Summary/Conclusion:A substantial number of patients with NDMM who are transplant eligible did not receive subsequent lines of therapy, with attrition by lines of therapy ranging from 23–40%. The increase in attrition rates with each additional line of therapy underscores the need to utilize upfront therapy associated with optimal progression‐free survival. Further studies evaluating the etiologic basis for this unexpectedly high attrition rate are warranted.image

Abstract Citron Rho-interacting serine/threonine kinase (CIT) is a serine/threonine kinase that acts as a key component of the midbody and is essential for cytokinesis. CIT has been reported to be highly expressed in some tumor tissues and to play a role in cancer proliferation; however, the significance of CIT has not been investigated in multiple myeloma (MM). Here, we identified, by protein microarray and immunohistochemistry, that CIT is 1 of the upregulated proteins in the plasma cells of MM patients compared with healthy controls. Analysis of a gene expression profile data set showed that MM patients with high CIT gene expression had significantly worse overall survival compared with MM patients with low CIT gene expression. CIT silencing in MM cell lines induced cytokinesis failure and resulted in decreased MM cell proliferation in vitro and in vivo. TP53 expression was found to be an independent predictor of CIT dependency, with low-TP53 cell lines exhibiting a strong dependency on CIT. This study provides the rationale for CIT being a potential therapeutic target in MM in future trials.

Abstract Chronic kidney disease is common in patients with multiple myeloma. Historically, individuals with end-stage renal disease and multiple myeloma did poorly with renal transplantation due to higher mortality rates from the malignancy itself or associated comorbidities. However, over the past 2 decades, there have been significant advances in the treatment of multiple myeloma with the advent of new therapeutic agents resulting in an improvement of long-term survival. As a result, more individuals with multiple myeloma are being referred for kidney transplantation, especially those with good functional capacity and minimal comorbidities. Recent literature has suggested that certain patients with multiple myeloma can successfully undergo renal transplantation after stem transplantation with consideration for maintenance therapy, although caution should be used with immunomodulating drugs due to the anecdotally reported risk of acute rejection. Therefore, having a multidisciplinary approach with the transplant team and hematology both before and after transplant is crucial in maximizing the chance of success for these individuals. This review summarizes the literature on renal transplantation in patients with multiple myeloma as well as the therapeutic advancements that have occurred which may allow certain patients to undergo successful transplantation.

98 Background: Survival probabilities for patients with multiple myeloma have increased considerably over the past several decades, and a conservative estimate of 5-year survival today is approximately 50%, perhaps higher with optimal treatment. Treatment options for multiple myeloma have grown significantly beginning in 2003 with the approval of bortezomib, followed by approvals for lenalidomide and thalidomide in 2006. The second wave of novel agent approvals began in 2012 with carfilzomib, followed by pomalidomide in 2013. The aim of this study was to estimate the survival gains associated with multiple myeloma therapies after the introduction of novel therapies beginning in 2003 in the United States. Methods: We estimated survival gains for multiple myeloma patients diagnosed in the 5-year period from 2010-2014—who had access to newer therapies like lenalidomide, bortezomib, pomalidomide, and carfilzomib—compared with patients diagnosed in the 5 years prior to the approval of bortezomib (1998–2002). We used data from the Surveillance, Epidemiology, and End Results (SEER) Program cancer registry and a generalized gamma regression survival model. The sample from SEER included patients aged > 18 years who had a diagnosis of multiple myeloma between 1983 and 2014. Results: Of 88,462 patients identified in the full sample, 14,446 patients were diagnosed in 1998–2002 and 25,948 patients were diagnosed in 2010–2014. Overall survival was 51% longer ( P< 0.001) in multiple myeloma patients diagnosed in 2010–2014 than in patients diagnosed in 1998–2002. Patients diagnosed in 2010–2014 had median and mean survival of 1.32 and 2.27 years longer, respectively, than patients diagnosed in 1998–2002. Conclusions: Patients diagnosed with multiple myeloma during 2010–2014 had significant improvement in survival relative to patients diagnosed in 1998–2002. This study found continued improvement in survival in multiple myeloma patients in the most recent 5-years of survival data available, demonstrating the considerable progress made since the wave of multiple myeloma innovation began in 2003.