Socioeconomic Status Is an Independent Prognostic Factor for Overall Survival in Patients With Multiple Myeloma: Real-World Data From a Cohort of 223 Patients

IntroductionSocioeconomic status (SES) has been shown to be a prognostic factor for overall survival in a variety of hematologic malignancies, especially for patients who require continuous care such as those with multiple myeloma (MM).Patients and MethodsWe retrospectively collected data from 223 patients with symptomatic MM diagnosed and treated in our department from January 2005 to December 2019. The modified Kuppuswamy scale, slightly modified, was used for the SES assessment. The Kaplan-Meier estimator of survival and Cox regression analysis were used.ResultsIn our cohort of 223 patients with MM, low SES was an independent poor prognostic factor for overall survival (OS), in addition to higher International Staging System stage and high-risk cytogenetics (hazard ratio for low SES on Cox regression analysis, 2.092; 95% confidence interval [CI], 1.36-3.2; log-rank P = .000). Patients with low SES had inferior survival compared with the whole patient cohort (median OS: low SES, 28 months; 95% CI, 18-37.9; high SES, 68 months; 95% CI, 55.6-80.4; log-rank P = .000). The low SES effect on OS was more evident for the elderly patients who were not transplant eligible and in those with a diagnosis of MM International Staging System stage I. The effect of low SES on OS was attenuated by time, and ethnic origin had no effect on OS.ConclusionsThe results of the present study have shown that low SES is an independent poor prognostic factor for survival of patients with MM.     

Patient Confidence and Information Preferences During the Treatment Decision-making Process: Results From a Large Multiple Myeloma Patient Survey Across 12 Countries in Europe and Israel

BackgroundThe relapsing nature of multiple myeloma (MM) means that patients typically receive different and multiple lines of therapy, requiring many treatment decisions over the disease course. The aim of this study was to explore patient confidence and information preferences during the treatment decision-making process.Patients and MethodsA multinational, cross-sectional survey enrolled patients with MM. It was co-developed and distributed by Myeloma Patients Europe across 12 countries in Europe and Israel from May 2019 to March 2020. Eligibility criteria included a self-reported diagnosis of MM and being able to recall the decision-making process at the start of their latest treatment line.ResultsA total of 1559 patients were included, with complete responses received from 1081 (69%) patients. The median age range was 54 to 64 years; there was an equal gender split and 57% had their latest treatment decision made within the past year. Overall, 54% of patients felt “very confident” in the latest treatment decision. Patients deemed the most important information to be safety/tolerability and treatment effectiveness, but the latter was among the least frequently received. Most patients reported that their primary physician treating MM was their main source for all types of information (range, 62%-94%), with 87% of patients reporting a “very good” or “good” relationship with them.ConclusionOver half of patients felt very confident in their latest treatment decision; however, patients reported not routinely receiving important treatment effectiveness information. Addressing the discrepancies between information that patients receive and consider important may enhance confidence in decision-making.     

Treatment Journeys of Patients With Newly Diagnosed Multiple Myeloma (NDMM): Results From The Connect MM Registry

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.

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Weekly Bortezomib,Pegylated Liposomal Doxorubicin,and Dexamethasone Is a Safe and Effective Therapy for Elderly Patients With Relapsed/Refractory Multiple Myeloma

BackgroundThe synergic, additive effect of bortezomib and pegylated liposomal doxorubicin (PLD) has never been tested in an elderly group of patients with relapsed/refractory multiple myeloma (MM).Patients and Methods:In this study, 25 patients with a median age of 75 years were treated with bortezomib at usual doses of 1.3 mg/m² every 21 days. After 2 cycles, bortezomib was given intravenously (I.V.) weekly every 32 days. Pegylated liposomal doxorubicin 30 mg/m² I.V. was given on day 4 for 2 cycles and then was given on day 8. Dexamethasone 40 mg I.V. was given on days 1-4 for 2 cycles and then 20 mg weekly.Results:Bortezomib/PLD/dexamethasone therapy resulted in 20 of 25 objective responses for an overall response rate of 80% (complete remission + very good partial remission, 66%). Median overall survival was not reached. Median duration of response (progression-free survival) was 8 months. Eleven of 16 patients (68%) with ≥ VGPR still maintain a response at a median of 12 months versus 4 months for patients with < VGPR (PFS, overall survival; P = .0001). Grade 3/4 toxicities were mild in most of the patients.ConclusionBortezomib/PLD/dexamethasone combination is safe and effective in elderly patients with resistant-relapsing MM.     

Patient Perceptions Regarding Ciltacabtagene Autoleucel Treatment: Qualitative Evidence From Interviews With Patients With Relapsed/Refractory Multiple Myeloma in the CARTITUDE-1 Study

IntroductionCiltacabtagene autoleucel (cilta-cel), a novel chimeric antigen receptor T (CAR-T) cell therapy, has demonstrated early, deep, and durable clinical responses in heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM), and improvements in health-related quality of life (HRQoL) in CARTITUDE-1 (NCT03548207). Patient perspectives on treatment provide context to efficacy outcomes and are an important aspect of therapeutic evaluation.MethodsQualitative interviews were conducted in a subset of CARTITUDE-1 patients (n = 36) at screening, Day 100, and Day 184 post cilta-cel on living with MM, therapy expectations, and treatment experiences during the study.ResultsPatients most wanted to see change in symptoms with the greatest impact on HRQoL: pain (85.2%) and fatigue (74.1%). The primary treatment expectation was achieving remission (40.7%), followed by extended life expectancy (14.8%). Patients most often defined meaningful change as improvement in symptoms (70.4%) and return to normalcy (40.7%). The percentage of patients reporting symptoms (pain, fatigue, bone fracture, gastrointestinal, neuropathy, and weakness) decreased from 85.2% to 22.2% across symptom types at baseline to 29.2% to 0% on Day 184 after cilta-cel. Improved symptoms and positive sentiments corresponded with improved perception of overall health status and reduced pain level, respectively. Most patients reported that their expectations of cilta-cel treatment had been met (70.8%) or exceeded (20.8%) at Day 184, and 70.8% of patients considered cilta-cel therapy better than their previous treatments.ConclusionOverall HRQoL improvements and qualitative interviews showed cilta-cel met patient expectations of treatment and suggest the long treatment-free period also contributed to positive sentiments.     

Prognostic Validation of SKY92 and Its Combination With ISS in an Independent Cohort of Patients With Multiple Myeloma

BackgroundHigh risk and low risk multiple myeloma patients follow a very different clinical course as reflected in their PFS and OS. To be clinically useful, methodologies used to identify high and low risk disease must be validated in representative independent clinical data and available so that patients can be managed appropriately. A recent analysis has indicated that SKY92 combined with the International Staging System (ISS) identifies patients with different risk disease with high sensitivity.Patients and MethodsHere we computed the performance of eight gene expression based classifiers SKY92, UAMS70, UAMS80, IFM15, Proliferation Index, Centrosome Index, Cancer Testis Antigen and HM19 as well as the combination of SKY92/ISS in an independent cohort of 91 newly diagnosed MM patients.ResultsThe classifiers identified between 9%-21% of patients as high risk, with hazard ratios (HRs) between 1.9 and 8.2.ConclusionAmong the eight signatures, SKY92 identified the largest proportion of patients (21%) also with the highest HR (8.2). Our analysis also validated the combination SKY92/ISS for identification of three classes; low risk (42%), intermediate risk (37%) and high risk (21%). Between low risk and high risk classes the HR is >10.     

Treatment Options for Patients With Heavily Pretreated Relapsed and Refractory Multiple Myeloma

Despite the increasing number of treatment options available for multiple myeloma, relapse is still inevitable and there remains a critical unmet need for treatments for patients with late-stage, highly refractory disease. In this review, we discuss currently approved treatment options for heavily pretreated patients with relapsed and refractory multiple myeloma, with a focus on the optimal management of patients with MM refractory to lenalidomide, bortezomib, and in some cases, daratumumab or an anti-CD38 monoclonal antibody. Data from recent clinical trials of immunomodulatory agents (pomalidomide), proteasome inhibitors (PIs; carfilzomib and ixazomib), monoclonal antibodies (elotuzumab, daratumumab, and isatuximab), and other novel therapies (including panobinostat-based therapy) are summarized. We also provide potential therapeutic strategies for patients according to different treatment histories, and include case studies to illustrate the practical use of various treatment options in a clinical setting. Regimens containing pomalidomide, elotuzumab, next-generation PIs, panobinostat, or selinexor may provide effective treatment options in patients with triple-refractory disease. The choice of agents used, and combinations thereof should be individualized as well as strategically planned from early- to late-stage relapse.     

Progressive Elevation of NT-ProBNP During Chemotherapy Is Related to Asymptomatic Cardiovascular Events in Patients With Multiple Myeloma

Background

Patients with multiple myeloma (MM) are at risk of cardiovascular events (CVEs) as a result of disease burden– and treatment-related risk factors. Cardiac biomarkers have been reported to be more sensitive than left ventricular ejection fraction in detecting CVEs. We sought to explore CVEs risk factors in MM patients and to establish sensitive predictors of biomarkers.

Pharmacokinetics-directed Intravenous Busulfan Combined With High-dose Melphalan and Bortezomib as a Conditioning Regimen for Patients With Multiple Myeloma

BackgroundHigh-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has a well-established role in the treatment of patients with multiple myeloma. Melphalan 200 mg/m² (Mel200) is the most commonly used preparative regimen. Several studies have provided evidence for potential synergism and safety when combining bortezomib (Btz) or busulfan (Bu) with melphalan (Mel).Patients and MethodsWe conducted a prospective phase II study to investigate the safety and efficacy of conditioning with pharmacokinetics (PK)-directed intravenous (IV) Bu with Btz and Mel. Bu dosing was adjusted to target a total area under the curve (AUC) of 20,000 μM × min. Patients received Btz (1 mg/m² × 4 doses) and Mel (140 mg/m²).ResultsA total of 19 subjects were enrolled. Their median age was 55 years, and the median follow-up period was 23.7 months. PK testing resulted in 86% of patients achieving an estimated total AUC of 20,000 ± 2500 μM × min. The overall response rate (ORR) at day +100 after ASCT was 100% in the evaluable patients, with 11% of patients achieving a complete response. The 2-year progression-free survival rate was 57.9% (95% confidence interval [CI], 38%-89%), and the 2-year overall survival rate was 88.5% (95% CI, 76%-100%). The most common grade 3 and 4 toxicities were febrile neutropenia, dysphagia/odynophagia, and oral mucositis. No case of hepatic sinusoidal obstruction syndrome developed. One treatment-related mortality occurred before day +100.ConclusionA preparative regimen of PK-directed IV Bu with Btz and Mel led to an ORR of 100% with acceptable toxicity and should be considered for direct comparison with the Mel200 regimen in future trials.     

Autologous Hematopoietic Cell Transplantation in Patients With Multiple Myeloma: Effect of Age

BackgroundIn the novel and pre–novel agent era, high-dose therapy, followed by autologous hematopoietic cell transplantation (AHCT), has been shown to prolong survival in patients with multiple myeloma (MM) in randomized trials. However, these trials only included patients aged ≤ 65 years. Given that the median age at diagnosis is 66 years, it is important to know the outcomes of AHCT in older patients. Similarly, definite outcomes of AHCT in very young patients (aged < 50 years) are also lacking because they represent a very small proportion of patients in clinical trials.Materials and MethodsWe analyzed a consecutive cohort of patients with MM receiving AHCT from 2000 to 2015 in 2 different age groups, older (> 70 years) and younger (≤ 50 years), and compared the outcomes. The primary objectives were to assess overall survival, progression-free survival (PFS), and nonrelapse mortality in these 2 groups.ResultsOf the 191 patients, 86 were young (age ≤ 50 years) and 105 were old (age > 70 years). The younger patients had better performance status and a lower comorbidity index, and most of the older patients had received a melphalan dose of 140 to 180 mg/m². The median follow-up period for the young group was 33 months (range, 2-164 months) compared with 22.5 months (range, 3-133 months) in the old group (P = .02). The PFS rate at 1 year was 60% (95% confidence interval [CI], 46%-72%) for the young group and 58% (95% CI, 45%-69%) for the old group. The overall survival rate at 1 year was 92% (95% CI, 84%-96%) for the young group and 85% (95% CI, 76%-91%) for the old group. On multivariate analysis, age did not have any effect on survival (P = .82); however, the patients with high-risk cytogenetics (hazard ratio [HR], 2.2; 95% CI, 1.06-4.6; P = .04) had worse overall mortality. High-risk cytogenetics (HR, 1.2; 95% CI, 1.1-3.5; P = .004) and no disease response or progressive disease at transplantation (HR, 5.0; 95% CI, 1.8-13.5; P = .02) were significantly associated with worse PFS.ConclusionAge should not be a limiting factor in considering the modality of AHCT. However, younger patients might also benefit from additional novel treatment approaches in the setting of clinical trials, given their similar outcomes with the older patients in our study.