Summary
Novel sequential combination therapy for induction may improve the quality of response and therefore prolong survival in newly diagnosed multiple myeloma (MM) patients. We report results from ...a phase 2 study of two sequential three‐drug combinations. Forty‐four previously untreated, symptomatic MM patients received: bortezomib 1·3 mg/m2 (days 1, 4, 8, 11), cyclophosphamide 300 mg/m2 (days 1, 8), plus dexamethasone 40 mg (day of and day after bortezomib) for three 21‐day cycles, followed by bortezomib 1·0 mg/m2, dexamethasone 40 mg and thalidomide 100 mg daily for three cycles. Overall response rate for 42 evaluable patients was 95%, including 19% stringent complete response (sCR), 26% CR, and 57%≥ very good partial response. Twenty‐two patients have undergone stem‐cell transplantation. After a median follow‐up of 20·9 months, five patients have died; none was induction therapy‐related. Median event‐free survival (EFS) and overall survival (OS) have not been reached; estimated 1‐year EFS and OS rates were 81% and 91% respectively. Both three‐drug combinations were well tolerated; 82% of patients completed all six cycles. Toxicities were predictable and manageable; the most‐commonly reported grade 3/4 toxicity was neuropathy (11%). This novel sequential three‐drug combination therapy is effective and well‐tolerated in previously untreated MM patients.
Adults with triple-class refractory (TCR) multiple myeloma (MM) have limited treatment options and poor prognosis, but the burden of TCR MM has not been well characterized. This study evaluated ...treatment patterns, overall survival (OS), health-related quality of life (HRQoL), and healthcare resource use (HCRU) among patients with TCR MM in US clinical practice.
Patients with TCR MM in the Connect MM Registry (NCT01081028; a large, US, multicenter, prospective observational cohort study of patients with newly diagnosed MM) were included. Patient characteristics, treatment patterns, HRQoL, and HCRU were analyzed using descriptive statistics. OS was calculated using Kaplan–Meier methodology for the overall cohort and for patients with/without ≥1 post-TCR line of therapy (LOT).
A total of 232 patients with TCR MM were included; 155 (67%) had ≥1 post-TCR LOT (post-TCR-Treated subgroup; median 9.9 months of follow-up). Most common post-TCR treatments were carfilzomib (47%), pomalidomide (40%), and daratumumab (26%); median treatment duration was 3.3 months. Median OS was 9.9 months in the overall population, 10.8 months in post-TCR-Treated patients, and 2.6 months for those with no new post-TCR LOT. HRQoL deteriorated and pain increased over 1 year of follow-up, with clinically meaningfully changes in EQ-5D (mean, –0.06 points) and FACT-G (mean, –9.9 points). 124 (53%) patients had ≥1 all-cause hospitalization and 58 (25%) had ≥1 MM-related hospitalization; median annualized length of stay was 35.3 and 42.9 days, respectively.
The burden of TCR MM is substantial, emphasizing the need for more effective treatment options in the TCR setting.
Patients with triple-class refractory multiple myeloma (TCR MM) have limited treatment options and poor prognosis. 232 patients with TCR MM in the Connect MM Registry showed poor overall survival, deteriorating health-related quality of life, increased pain, and frequent long hospitalizations over 1 year of follow-up. The burden of TCR MM is substantial, emphasizing a need for better treatments.
Multiple myeloma (MM) patients have increased risk of severe coronavirus disease 2019 (COVID-19) when infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Monoclonal gammopathy ...of undetermined significance (MGUS), the precursor of MM has been associated with immune dysfunction which may lead to severe COVID-19. No systematic data have been published on COVID-19 in individuals with MGUS. We conducted a large population-based cohort study evaluating the risk of SARS-CoV-2 infection and severe COVID-19 among individuals with MGUS. We included 75,422 Icelanders born before 1976, who had been screened for MGUS in the Iceland Screens Treats or Prevents Multiple Myeloma study (iStopMM). Data on SARS-CoV-2 testing and COVID-19 severity were acquired from the Icelandic COVID-19 Study Group. Using a test-negative study design, we included 32,047 iStopMM participants who had been tested for SARS-CoV-2, of whom 1754 had MGUS. Among these participants, 1100 participants, tested positive, 65 of whom had MGUS. Severe COVID-19 developed in 230 participants, including 16 with MGUS. MGUS was not associated with SARS-CoV-2 infection (Odds ratio (OR): 1.05; 95% confidence interval (CI): 0.81-1.36; p = 0.72) or severe COVID-19 (OR: 0.99; 95%CI: 0.52-1.91; p = 0.99). These findings indicate that MGUS does not affect the susceptibility to SARS-CoV-2 or the severity of COVID-19.
Micro-Abstract In this analysis, we focused on the importance of establishing baseline characteristics in multiple myeloma patients in the Connect MM registry. Variations were observed in the ...percentage of reported baseline data. Creating solid records of baseline patient disease characteristics using suggested National Comprehensive Cancer Network diagnostic work-up and International Myeloma Working Group criteria provides a foundation for monitoring disease progression and response to treatment.
Background
The Surveillance, Epidemiology, and End Results (SEER) database and National Cancer Database (NCDB) show improved overall survival (OS) in patients with multiple myeloma (MM) over the last ...15 years. This analysis evaluated the validity of the largely community‐based Connect MM Registry as a national reference for MM.
Methods
Baseline disease characteristics and survival in US newly diagnosed MM patients were examined using the Connect MM Registry as well as SEER and NCDB databases. Baseline characteristics predictive of longer survival in Connect MM were also identified.
Results
As of February 2017, 3011 patients were enrolled in the Connect MM Registry; 2912 were treated. Median age at time of MM diagnosis and age range were numerically similar from 2010 to 2015 across all 3 registries; SEER had a higher representation of nonwhite racial groups than that in the other 2 registries. OS rates suggest proportionate improvement with year of diagnosis among the 3 registries. A Cox proportional hazards model suggests that younger age (<65 years) is associated with longer survival (vs ≥75; HR, 0.39; 95% confidence interval, 0.34‐0.46) in the Connect MM Registry. However, sex (HR, 0.91; P = .15) and race (black vs white; HR, 0.88; P = .21) were not associated with longer OS.
Conclusions
Data from the Connect MM Registry appear to be largely representative of national trends, comprehensive, and reliable representations of the national MM population. Baseline characteristics were comparable, and survival similarly improved over time among the 3 registries.
ClinicalTrials.gov, identifier
NCT01081028.
Survival data from the Connect MM Registry, which is representative of the national MM population, reflect national trends of improvement. This establishes the Connect MM Registry as a reference for MM survival in the US.
Radiation therapy (RT) is an important treatment modality for patients with multiple myeloma (MM). Although patients are living longer with MM, they are more likely to have comorbidities related to ...treatment, such as bone pain; however, RT can provide symptom relief. To date, the characterization of patients who have received RT in the real-world setting has been limited.
The Connect® MM Registry is a large, US multicenter, prospective observational cohort study of adult patients with newly diagnosed MM from mostly community sites. RT utilization and outcomes were analyzed quarterly throughout treatment. Factors associated with RT use were identified via multivariable analysis.
A total of 3011 patients were enrolled in the Connect MM Registry with 903 patients (30%) having received RT at any time. There was a significant difference (P < .05) in overall RT use among patients with an Eastern Cooperative Oncology Group performance status of 0 to 1 versus ≥2, International Staging System disease stage I/II versus III, a history of plasmacytoma or a novel agent in their first regimen, and any number of bone lesions or severe osteoporosis/fracture. RT use was associated with having bone lesions or severe osteoporosis (vs not having bone lesions). Additionally, RT use was associated with ethnicity (Hispanic vs not) and Connect MM Registry cohort (cohort 1 enrolled 2009-2011 vs 2 enrolled 2012-2016). In the 6 months before death, increased RT use was associated with increasing number of treatment lines (P < .0001) and high- versus standard-risk disease (per International Myeloma Working Group criteria; P = .0028).
Real-world results from the Connect MM Registry show RT is frequently used and is associated with clinical factors, including performance status and disease stage. Earlier in MM diagnosis, RT may be used as an adjunct to palliate symptoms or delay systemic therapy. Toward the end of life, RT is more frequently used for palliation when treatment options are often limited.
Background： The efficacy and safety evidence of bortezomib in multiple myeloma （MM） patients with hepatitis B is vacant.This study aimed to investigate the efficacy and safety of bortezomib in MM ...patients with hepatitis B in China.Methods： From 2006 to 2011, 739 newly diagnosed MM patients were screened for serum hepatitis B virus （HBV） biomarkers.HBV-infected patients were followed for HBV reactivation by monitoring of serum alanine transaminase （ALT） and HBV DNA load.The pattern of HBV reactivation in relation to bortezomib was evaluated.Seven hundred thirty-nine MM patients were included in this study.Results： The prevalence of MM patients infected with HBV was 3.4% （n =25）, of which 17 cases were treated with bortezomib.Bortezomib had no significant influence on liver function （ALT before and after treatment： 36.69 ＆#177; 8.90 U/L vs.11.31 ＆#177; 2.74 U/L, P =0.19） and HBV DNA of MM patients with HBV （detectable HBV DNA percentage： 5.9% vs.11.8%, P =0.12）.Conclusions： Bortezomib can be used safely and effectively in MM patients with hepatitis B.HBV prophylaxis and surveillance are recommended during the MM treatment.
Maintenance therapy after autologous stem cell transplantation (ASCT) improves clinical outcomes in multiple myeloma (MM), but the effect of continued treatment with lenalidomide-only maintenance, or ...any maintenance, on health care resource utilization (HCRU) is largely unknown.
Here we present an analysis of HCRU and clinical outcomes in a cohort of patients from the Connect MM registry, the largest, ongoing, observational, prospective US registry of patients with symptomatic newly diagnosed MM. In this study, patients with newly diagnosed MM who completed induction and single ASCT without subsequent consolidation received lenalidomide-only maintenance (n = 180), any maintenance (n = 256), or no maintenance (n = 165). HCRU (hospitalization, surgery/procedures, and concurrent medications growth factors, bisphosphonates, or neuropathic pain medication) was assessed starting from 100 days post-ASCT for up to 2 years.
Although the rates of hospitalization per 100 person-years were similar across groups at the end of years 1 and 2, the median duration of hospitalization was numerically longer with no maintenance. The rates of use of growth factors, bisphosphonates, and neuropathic pain medication were generally similar in all 3 groups. The receipt of any maintenance was associated with significantly reduced use of neuropathic pain medications during year 1. Of note, lenalidomide-only maintenance was associated with significantly longer progression-free survival (54.5 vs 30.4 months; hazard ratio HR = 0.58; 95% CI, 0.43–0.79; P = 0.0005) and overall survival (OS) (median OS not reached in either group; HR = 0.45; 95% CI, 0.28–0.73; P = 0.001) compared with no maintenance. Likewise, the group treated with any maintenance had significantly longer median progression-free survival (44.7 vs 30.4 months; HR = 0.62; 95% CI, 0.47–0.82; P = 0.0008) and OS (median OS not reached in either group; HR = 0.50; 95% CI, 0.33–0.76; P = 0.001) than did the group that did not receive maintenance.
These findings suggest that in this largely community-based study population, post-ASCT maintenance therapy, including lenalidomide-only maintenance, improves clinical outcomes without negatively affecting HCRU. ClinicalTrials.gov identifier: NCT01081028.
A venous thromboembolism (VTE) with the subsequent risk of pulmonary embolism is a major concern in the treatment of patients with multiple myeloma with thalidomide. The susceptibility to developing ...a VTE in response to thalidomide therapy is likely to be influenced by both genetic and environmental factors. To test genetic variation associated with treatment related VTE in patient peripheral blood DNA, we used a custom-built molecular inversion probe (MIP)–based single nucleotide polymorphism (SNP) chip containing 3404 SNPs. SNPs on the chip were selected in “functional regions” within 964 genes spanning 67 molecular pathways thought to be involved in the pathogenesis, treatment response, and side effects associated with myeloma therapy. Patients and controls were taken from 3 large clinical trials: Medical Research Council (MRC) Myeloma IX, Hovon-50, and Eastern Cooperative Oncology Group (ECOG) EA100, which compared conventional treatments with thalidomide in patients with myeloma. Our analysis showed that the set of SNPs associated with thalidomide-related VTE were enriched in genes and pathways important in drug transport/metabolism, DNA repair, and cytokine balance. The effects of the SNPs associated with thalidomide-related VTE may be functional at the level of the tumor cell, the tumor-related microenvironment, and the endothelium. The clinical trials described in this paper have been registered as follows: MRC Myeloma IX: ISRCTN68454111; Hovon-50: NCT00028886; and ECOG EA100: NCT00033332.
Sankey plots were generated to illustrate the heterogeneity of treatment sequences and transitions over time in real-world patients from the Connect Multiple Myeloma (MM) Registry. Plots identified ...immunomodulatory agents and proteasome inhibitors as the mainstays of treatment for patients who did or did not receive stem cell transplant. More patients received stem cell transplant (shown above) and continued to second-line treatment, which highlights the need to choose optimal first-line regimens – particularly for patients without a transplant intent. Abbreviations: IMiD = Immunomodulatory imide; 1L = first-line; 3L = third-line; PFS = progression-free survival; PI = proteasome inhibitor; SCT = stem cell transplant. Display omitted
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