Rajkumar, S. Vincent

AbstractPatients with light chain amyloidosis (AL) often have delayed diagnosis and present with significant symptomatology; this may result in decreased quality of life (QOL). We prospectively employ a “Hematology Patient Reported Symptom Screen” (HPRSS), which is three questions about fatigue, pain, and QOL, scored 0–10. The aim of this study is to better understand QOL and determine if HPRSS parameters predict for clinical outcomes. From 2009 to 2014, 302 newly diagnosed AL patients were included. Baseline median scores [interquartile range] for fatigue, pain, and QOL were 6 [3,7], 2 [0,5], 5 [3,8], respectively. Median overall survival was 53 months, with 102 (34%) deaths in the first year. There were significant differences in baseline HPRSS between those that lived longer than one year and early death patients in the domains of fatigue (5 [IQR 3, 7] vs. 7 [IQR 5, 8], P < 0.0001) and QOL (6 [IQR 4, 8] vs. 5 [IQR 3, 7], P = 0.006). On univariate analysis fatigue, QOL, physician‐reported performance status, autologous stem cell transplant (ASCT), and Mayo stage were prognostic for survival. On multivariate analysis Mayo stage, ASCT, and baseline fatigue remained independently prognostic. When analyses were restricted to the 125 patients with HPRSS measurements at 12 months, we found that over time QOL scores improved significantly 6 [IQR 3.5, 8] → 7 [IQR 5, 8] (P = 0.01). Asking AL patients to rate their fatigue and QOL has predictive value. Baseline patient reported fatigue is an independent prognostic factor for survival. Survival at one year was associated with significant improvement in QOL.

Key Points Significant improvement in outcome is a reality for newly diagnosed AL amyloidosis in the past decade. Six-month mortality among transplant ineligible patients has declined since 2005.

Objectives: To describe the clinical presentation, radiological features, and outcome of patients with plasmacytoma of the temporal bone. Methods: Multicenter retrospective case series of all patients diagnosed with plasmacytoma of the temporal bone between 1990 and 2015. Comprehensive literature review of all previously published cases. Results: A total of seven patients (average age, 57.3 yr; 57% women) met inclusion criteria. Three (43%) had a known history of multiple myeloma (MM). The most common symptoms at presentation included otalgia, headache, and dizziness (43%, each). Five (71%) presented with a vascular appearing middle ear mass visible on otoscopy. Four of these patients did not have an established history of MM and were referred with presumptive diagnoses of paraganglioma or endolymphatic sac tumor (ELST). The average maximum tumor diameter was 3.7 cm (median, 3.5 cm; range, 0.9–6.6 cm) and the most commonly involved temporal bone subsites were the middle ear and mastoid (71% each). MM was ultimately diagnosed in six cases (86%). In addition to the new cases presented herein, 18 previously published reports were analyzed. In the 25 aggregate cases, 44% of cases were associated with MM, and the mastoid (72%) and middle ear (53%) were the most commonly involved temporal bone subsites. Conclusion: Plasmacytoma of the temporal bone is rare, and the clinical presentation can closely mimic that of other primary temporal bone tumors. In patients with an established history of MM, it is imperative to have a high index of suspicion for temporal bone plasmacytoma, even when radiological features suggest an alternate diagnosis.

Abstract Over the past few years, the management of multiple myeloma has changed. We have new guidelines regarding how to set the diagnosis, when to initiate therapy, and how to monitor treatment response. In 2014, the updated International Myeloma Working Group (IMWG) diagnostic criteria changed the definition of multiple myeloma from being a disease defined by symptoms to a disease defined by biomarkers. Today, modern combination therapies have reported up to 60% to 80% of patients reaching a complete response. As a logical and necessary step forward, investigators have explored strategies to detect minimal residual disease (MRD) and its correlation with clinical outcomes. Recent meta-analysis data show that MRD negativity is associated with longer progression-free survival and overall survival. In 2016, the updated IMWG response criteria include MRD as the deepest level of treatment response in multiple myeloma. Simultaneously, we are still quite behind in our understanding of the heterogeneous biology of multiple myeloma and its implications for therapy. Emerging DNA sequencing data show that newly diagnosed multiple myeloma patients have a broad range of mutations, which are distributed unevenly in multiple parallel subclones already present at diagnosis. To move beyond the ill-defined category of “high-risk multiple myeloma,” which confers to approximately 25% of all newly diagnosed patients, prospective studies are needed to dissect tumor biology and define multiple myeloma subtypes, and, based on biology, seek to define rational therapies for individual subtypes. This article discusses novel insights and gives perspectives on diagnosis and MRD monitoring and future directions for prognosis and clinical management of multiple myeloma. Clin Cancer Res; 22(22); 5428–33. ©2016 AACR. See all articles in this CCR Focus section, “Multiple Myeloma: Multiplying Therapies.”

Abstract Advances in the diagnosis and treatment of multiple myeloma have come at a rapid pace, especially with several new drugs entering the market in the last few years. However, access to and affordability of new treatments poses a major challenge, both in the United States and around the world. High costs of life-saving drugs are detrimental to both the personal finances of the individual patient, as well as society which must bear the increasing costs in terms of increased health insurance premiums, taxes, or both. The challenges are not unique to myeloma, but are commonly encountered in several other cancers as well. But to some extent these pharmacoeconomic concerns are amplified in myeloma due to the need for multidrug regimens that combine 2 or more expensive new drugs, continuous therapy, and the prolonged disease course in most patients. We examine current myeloma therapy from a pharmacoeconomic perspective, and discuss the costs involved. We outline the underlying reasons why cancer drugs are so expensive, the measures that are required to lower cost, and propose potential ways in which costs can be reduced while still delivering high-quality care.

A preclinical study demonstrated anti‐proliferative and apoptotic effect of propranolol on multiple myeloma (MM) cell. Clinical studies suggested that beta‐blocker (BB) might impact the prognosis of breast, prostate, colorectal, ovarian, lung, and skin cancer. This retrospective study evaluated the effect of BB in MM disease‐specific survival (DSS) and overall survival (OS). Among 1,971 newly diagnosed MM patients seen at Mayo Clinic between 1995 and 2010, usage of BB and other cardiac (or antihypertensive) medications were abstracted. Cumulative incidence function and Kaplan–Meier method were used to estimate 5‐year cumulative incidence rate (CIR) of MM death and OS rate, respectively. Nine hundred and thirty (47.2%) patients had no intake of cardiac medications; 260 (13.2%) used BB alone; 343 (17.4%) used both BB/non‐BB cardiac medications; and 438 (22.2%) had non‐BB cardiac drugs. Superior MM DSS was observed in BB only users, compared to patients without any cardiac drugs ( , 0.53, 95% confidence interval [CI], 0.42–0.67, Padj.<0.0001) and non‐BB cardiac drugs users ( , 0.49, 95% CI, 0.38–0.63, Padj.<0.0001). Patients on both BB and other cardiac drugs showed superior DSS than non‐cardiac drugs users ( , 0.54, 95% CI, 0.44–0.67, Padj.<0.0001) and non‐BB cardiac drug users. ( , 0.50, 95% CI, 0.40–0.62, Padj.<0.0001). MM DSS did not differ between BB users with and without other cardiac drugs (Padj.=0.90). Multivariable analysis showed the same pattern for OS. In patients with MM, BB intake is associated with a reduced risk of disease‐specific death and overall mortality in comparison to non‐BB or no use of cardiac drugs. Am. J. Hematol. 92:50–55, 2017. © 2016 Wiley Periodicals, Inc.

Key PointsThe monotypic and polytypic PC compartments assessed by MFC are prognostic in AL amyloidosis. MFC may play a role in the definition of hematologic response to treatment.