Evaluation to Prognostic Staging System of Multiple Myeloma in Novel Agent Era

Author(s):  
Yufeng Shang ◽  
Yanxia Jin ◽  
Hailing liu ◽  
Lu Ding ◽  
Xiqin Tong ◽  
...  

Abstract Purpose This study was to evaluate existing staging system of multiple myeloma (MM) in the real world. Methods We retrospectively analyzed 886 newly diagnosed MM from two institutions. Results The overall survival (OS) of eligible patients was 61.0 months. R-ISS held a larger receiver operating characteristic curve (ROC) area (0.603) than that of ISS (0.573) and DS staging system (0.567). In the group of immunomodulatory agents-based regimens, the median OS was 92.0 months in R-ISS I, 63.0 months in R-ISS II and 18.0 months in R-ISS III (p<0.0001). In the group of proteasome inhibitors-based regimens, the median OS was 102.0 months in R-ISS I, 63.0 months in R-ISS II and 22.0 months in R-ISS III (p<0.0001). In different subgroups grouped according to Age, HGB, CREA and Ca, R-ISS also had a good stratification effect. Patients in R-ISS II were further analyzed, which accounted for 69.9% of all R-ISS patients. Using univariable and multivariable Cox analysis, Age>65 years (p=0.001), HGB<100g/L (p<0.001), elevated LDH (p=0.001) and Ca (p=0.010) were independent factors indicating worse prognosis for R-ISS II. Conclusion R-ISS remains a valuable staging system in the real world of new drug era. But patients classified in R-ISS II still have large heterogeneity.

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258487
Author(s):  
Agoston Gyula Szabo ◽  
Tobias Wirenfeldt Klausen ◽  
Mette Bøegh Levring ◽  
Birgitte Preiss ◽  
Carsten Helleberg ◽  
...  

Most patients cannot be included in randomized clinical trials. We report real-world outcomes of all Danish patients with multiple myeloma (MM) treated with daratumumab-based regimens until 1 January 2019. Methods Information of 635 patients treated with daratumumab was collected retrospectively and included lines of therapy (LOT), hematologic responses according to the International Myeloma Working Group recommendations, time to next treatment (TNT) and the cause of discontinuation of treatment. Baseline characteristics were acquired from the validated Danish Multiple Myeloma Registry (DMMR). Results Daratumumab was administrated as monotherapy (Da-mono) in 27.7%, in combination with immunomodulatory drugs (Da-IMiD) in 57.3%, in combination with proteasome inhibitors (Da-PI) in 11.2% and in other combinations (Da-other) in 3.8% of patients. The median number of lines of therapy given before daratumumab was 5 for Da-mono, 3 for Da-IMiD, 4 for Da-PI, and 2 for Da-other. In Da-mono, overall response rate (ORR) was 44.9% and median time to next treatment (mTNT) was 4.9 months. In Da-IMiD, ORR was 80.5%, and mTNT was 16.1 months. In Da-PI, OOR was 60.6% and mTNT was 5.3 months. In patients treated with Da-other, OOR was 54,2% and mTNT was 5.6 months. The use of daratumumab in early LOT was associated with longer TNT (p<0.0001). Patients with amplification 1q had outcome comparable to standard risk patients, while patients with t(4;14), t(14;16) or del17p had worse outcome (p = 0.0001). Multivariate analysis indicated that timing of treatment (timing of daratumumab in the sequence of all LOT that the patients received throughout the course of their disease) was the most important factor for outcome (p<0.0001). Conclusion The real-world outcomes of multiple myeloma patients treated with daratumumab are worse than the results of clinical trials. Outcomes achieved with daratumumab were best when daratumumab was used in combination with IMIDs and in early LOT. Patients with high-risk CA had worse outcomes, but patients with amp1q had similar outcomes to standard-risk patients.


2021 ◽  
pp. 107815522199553
Author(s):  
Joshua Richter ◽  
Vamshi Ruthwik Anupindi ◽  
Jason Yeaw ◽  
Suneel Kudaravalli ◽  
Stojan Zavisic ◽  
...  

Introduction Real-world evidence on later line treatment of relapsed/refractory multiple myeloma (RRMM) is sparse. We evaluated clinical outcomes among RRMM patients in the 1-year following treatment with pomalidomide or daratumumab and compared economic outcomes between RRMM patients and non-MM patients. Patient and Methods Adult patients with ≥1 claim of pomalidomide or daratumumab were identified between January 2012 and February 2018 using IQVIA PharMetrics® Plus US claims database. Patients were required to have a diagnosis or treatment for MM and a claim of any immunomodulatory drugs and proteasome inhibitors before the index date. Mean time to new therapy, overall survival (OS) using Kaplan-Meier curve and adverse events (AEs) were reported over the 1-year post-index period. RRMM patients were also matched to a non-MM comparator cohort and economic outcomes were compared between the two cohorts. Results 289 RRMM patients were matched to 1,445 patients without MM. Most prevalent hematological AE was anemia (72.0%) and non-hematological AE was infections (75.4%). Mean (SD) time to a new treatment was 4.7 (5.3) months and median OS was 14.6 months. RRMM patients had significantly higher hospitalizations and physician office visits (Both P < .0001) compared to non-MM patients. Adjusting for baseline characteristics, patients with RRMM had 4.9 times (95% CI 3.8-6.4, P < .0001) the total healthcare costs compared with patients without MM. The major driver of total costs among RRMM patients was pharmacy costs (67.3%). Conclusion RRMM patients showed a high frequency of AEs, low OS, and a substantial economic burden suggesting need for effective treatment options.


Author(s):  
Aaron N. Winn ◽  
Gunjan L. Shah ◽  
Joshua T. Cohen ◽  
Pei-Jung Lin ◽  
Susan K. Parsons

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18727-e18727
Author(s):  
Robert Smith ◽  
Mei Xue ◽  
Natalie Dorrow ◽  
Prateesh Varughese ◽  
Cosima Hogea ◽  
...  

e18727 Background: Treatment for multiple myeloma (MM) over the past decade has significantly improved survival. In particular, 3 drug classes have altered the treatment paradigm for MM patients: proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and CD38 monoclonal antibodies (anti-CD38s). Despite these advances, the majority of patients with MM will become refractory to PIs, IMiDs, and anti-CD38s, and limited evidence indicates these patients have poor outcomes. A retrospective study in the US showed that 275 patients treated at 14 academic institutions with prior exposure to a PI, IMiD, and anti-CD38 had median overall survival of 9.2 months. The aim of this study was to evaluate real-world treatment patterns and outcomes (duration of therapy and overall survival) of patients who had been treated with a PI, IMiD, and anti-CD38 in community practices in the US. Methods: This retrospective observational study was conducted using the Integra Connect (IC) database. The IC database includes electronic health data from structured and unstructured fields from 12 community practices on the East and West Coast of the US. Adult patients with ≥2 ICD-9/ICD-10 codes for MM on at least 2 separate dates, who received MM treatment between Jan 1, 2016, and Dec 31, 2019, with treatment history that included at least one PI, one IMiD, and one anti-CD38 (triple exposed), and initiated a subsequent line of therapy (s-LOT) after becoming triple exposed, were included. Duration of length of s-LOT was defined as number of days from start of s-LOT to last-day supply of s-LOT. Overall survival was defined as the length of time from start of s-LOT through death or the date of the last office visit. Results: A total of 501 patients were included in this analysis. The median age of patients was 64.9 years; 50% were male; 50% had commercial insurance. 82.8% of patients had ECOG 0 or 1 at diagnosis and had received a median of 3 prior lines of therapy (LOTs) before initiating s-LOT. Prior to initiating s-LOT, 91% had been exposed to bortezomib, 81% to carfilzomib, 94% to lenalidomide, 82% to pomalidomide, and 100% to daratumumab. In s-LOT, 95% received treatment that included same drug or same drug class (30% received bortezomib, 48% carfilzomib, 31% lenalidomide, 47% pomalidomide, and 31% daratumumab). The median duration of s-LOT was 78 days and median survival was 10.3 months (308 days) from initiation of s-LOT. Conclusions: For triple-class exposed patients, there is a lack of consensus on the most efficacious approach to subsequent treatment. The present study shows a significant amount of retreatment with previously used agents or classes among these patients with short duration of therapy and poor survival. As has been previously noted, new strategies and agents targeting novel aspects of MM are needed to improve outcomes for these patients. Disclosures: This study (213286) was sponsored by GlaxoSmithKline.


2018 ◽  
Vol 46 (6) ◽  
pp. 2230-2237
Author(s):  
Jun Xia ◽  
Lingling Wang ◽  
Xin Zhou ◽  
Jing Wang ◽  
Huan Wang ◽  
...  

Objectives This study was performed to analyze the risk factors for early mortality (EM) in elderly patients undergoing treatment for multiple myeloma (MM) in real-world clinical practice. Methods Retrospective data from 108 elderly patients who were newly diagnosed with MM from January 2007 to July 2015 were analyzed in a single hematology center. EM was defined as death of any cause within 12 months after diagnosis. A multivariate regression model was used to evaluate EM. Results EM occurred in 16 (14.8%) elderly patients with newly diagnosed MM. The most common cause of death was infection (10/16, 62.5%). In the multivariate analysis, only an age of ≥75 years, International Staging System (ISS) stage III disease, and high lactate dehydrogenase concentration were significantly and independently associated with EM. Conclusion Our results suggest that infection is the leading cause of EM in elderly patients with MM. An age of ≥75 years, ISS stage III disease, and a high lactate dehydrogenase concentration are significant predictors of EM. We should further target this higher-risk patient population to define personalized therapy with which to improve outcomes.


Author(s):  
Faith Davies ◽  
Robert Rifkin ◽  
Caitlin Costello ◽  
Gareth Morgan ◽  
Saad Usmani ◽  
...  

AbstractMultiple available combinations of proteasome inhibitors, immunomodulators (IMIDs), and monoclonal antibodies are shifting the relapsed/refractory multiple myeloma (RRMM) treatment landscape. Lack of head-to-head trials of triplet regimens highlights the need for real-world (RW) evidence. We conducted an RW comparative effectiveness analysis of bortezomib (V), carfilzomib (K), ixazomib (I), and daratumumab (D) combined with either lenalidomide or pomalidomide plus dexamethasone (Rd or Pd) in RRMM. A retrospective cohort of patients initiating triplet regimens in line of therapy (LOT) ≥ 2 on/after 1/1/2014 was followed between 1/2007 and 3/2018 in Optum’s deidentified US electronic health records database. Time to next treatment (TTNT) was estimated using Kaplan-Meier methods; regimens were compared using covariate-adjusted Cox proportional hazard models. Seven hundred forty-one patients (820 patient LOTs) with an Rd backbone (VRd, n = 349; KRd, n = 218; DRd, n = 99; IRd, n = 154) and 348 patients (392 patient LOTs) with a Pd backbone (VPd, n = 52; KPd, n = 146; DPd, n = 149; IPd, n = 45) in LOTs ≥2 were identified. More patients ≥75 years received IRd (39.6%), IPd (37.8%), and VRd (36.7%) than other triplets. More patients receiving VRd/VPd were in LOT2 vs other triplets. Unadjusted median TTNT in LOT ≥ 2: VRd, 13.9; KRd, 8.7; IRd, 11.4; DRd, not estimable (NE); and VPd, 12.0; KPd, 6.7; IPd, 9.5 months; DPd, NE. In covariate-adjusted analysis, only KRd vs DRd was associated with a significantly higher risk of next LOT initiation/death (HR 1.72; P = 0.0142); no Pd triplet was significantly different vs DPd in LOT ≥ 2. Our data highlight important efficacy/effectiveness gaps between results observed in phase 3 clinical trials and those realized in the RW.


CMAJ Open ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. E1141-E1148
Author(s):  
Rukia Swaleh ◽  
Taylor McGuckin ◽  
Tyler W. Myroniuk ◽  
Donna Manca ◽  
Karen Lee ◽  
...  

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4745-4745
Author(s):  
Humberto Martinez-Cordero ◽  
Virginia Abello ◽  
William Armando Mantilla Duran ◽  
Rigoberto Gomez ◽  
Jheremy Reyes ◽  
...  

Abstract Background Proteasome inhibitors (PIs) are approved for treating newly diagnosed and relapsed multiple myeloma (MM) in Colombia. This propensity score matching (PSM) analysis using data from the real-world, was designed to establish the role PIs (bortezomib or carfilzomib) at first relapsed or refractory MM. The primary endpoint was overall response rate (ORR) and secondary endpoint included was overall survival (OS). Moreover, an analysis of OS was done regarding response attained. On Behalf of RENEHOC-GRIMMCO (Colombian Registry for Hemato-Oncological Diseases and Colombian Mieloma Múltiple study group). Methods PSM by nearest neighbor analysis to evaluate the role of PIs used at first relapse in multiple myeloma of patients belonging to RENEHOC registry, between 2010 and 2020. Results 390 patients were identified in the first relapse of the Colombian registry, 269 patients with PI and 121 patients without PI. One hundred and ten patients were included in each group after PSM. Patients were matched for age, ISS, extramedullary disease, and use of lenalidomide to define the influence of this immunomodulatory drug in the PI group. A difference was found in the use of lenalidomide because only 1 patient was treated with PI and lenalidomide concomitantly (0.91%) compared to 31 patients in the group without PI (28.18%), (p &lt;0, 0001). Regarding ORR, no differences were found between the 2 groups 38.18% in PIs vs 37.27% in non-PIs group (p = 0.801). A trend towards better OS was found in the PIs group with a median of 58 months versus 39 months (p = 0.179). Overall survival in patients who achieved at least PR was better compared to those who did not reach 79 months versus 32 months in non-responders (p = 0.0001). Conclusion In this study, we found that the use of PI has a tendency to improve overall survival in real-world in MM patients when used in the first relapse and that this effect could possibly be enhanced with the combination with lenalidomide. Regardless of the treatment used, better responses are associated with better survival. Figure 1 Figure 1. Disclosures Abello: Janssen: Honoraria; Amgen: Honoraria; Dr Reddy's: Research Funding. Sossa: Amgen: Research Funding.


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