Multiple myeloma, a cancer of older adults, has seen significant improvement in therapeutic options over the past two decades. Uncovering disparities in treatment patterns and outcomes is imperative ...in order to ensure older adults, who are underrepresented in clinical trials, are benefitting from these advances.
Adults with newly diagnosed multiple myeloma (NDMM) were identified using linked provincial administrative databases between 2007 and 2017 in Ontario, Canada. Trends in rate of no treatment, novel drug and autologous stem cell transplant (ASCT) usage was evaluated within one year following diagnosis along with the associated early mortality (<12 months) for the aforementioned cohorts among younger (≤65 years) and older adults (>65 years) with NDMM.
A total of 8841 adults with NDMM were identified. Rates of no treatment decreased in both age groups during the study period; however still remain considerably high among older patients (from 34.9% in 2007 to 27.4% in 2017) with high associated early mortality in the older untreated group (54.1% 1 yr mortality over study period). Despite increased usage of novel drugs in both age groups, early mortality decreased among younger patients utilizing novel drugs (16.1% to 5.6%) but remained high and stagnant in older patients using novel drugs (18.2% 1 yr mortality over study period). ASCT utilization increased in both age groups during the study period with decreasing early mortality among older patients undergoing ASCT (from 26.3% in 2007 to 1.1% in 2017).
While several improvements have been made, rates of no treatment and early mortality among patients not treated and those started on novel drugs remains a concern in older adults with NDMM.
Summary
Venous thromboembolism (VTE) has an increased incidence in patients with multiple myeloma (MM), especially during chemotherapy. Mechanisms including upregulation of procoagulant factors, such ...as factor VIII, have been postulated. The National Cancer Institute of Canada Clinical Trials Group MY.10 phase III clinical trial compared thalidomide‐prednisone to observation for 332 patients with MM post‐autologous stem cell transplantation (ASCT), with a primary endpoint of overall survival and various secondary endpoints including the incidence of VTE. One hundred and fifty‐three patients had biomarker data, including D‐dimer, factor VIII and thrombin anti‐thrombin (TAT) levels collected post‐ASCT at baseline and 2 months after intervention investigating in‐vivo thrombin generation. Differences between the time‐points included a significant reduction over time in D‐dimer, factor VIII and TAT levels in the observation group and sustained elevation of D‐dimer, significant increase in factor VIII and reduction in TAT levels in the thalidomide‐prednisone group. Eight VTE events were reported in this subset of study patients, all in the thalidomide‐prednisone arm, with a trend to increase in D‐dimer levels over time in those patients with VTE. This study provides physiological and clinical evidence for an increased risk of VTE associated with thalidomide‐prednisone maintenance therapy post‐ASCT for MM.
The NCIC CTG LY.12 study showed that gemcitabine, dexamethasone, and cisplatin (GDP) were noninferior to dexamethasone, cytarabine, and cisplatin (DHAP) in patients with relapsed or refractory ...aggressive histology lymphoma prior to autologous stem cell transplantation. We conducted an economic evaluation from the perspective of the Canadian public healthcare system based on trial data.
The primary outcome was an incremental cost utility analysis comparing costs and benefits associated with GDP vs DHAP. Resource utilization data were collected from 519 Canadian patients in the trial. Costs were presented in 2012 Canadian dollars and disaggregated to highlight the major cost drivers of care. Benefit was measured as quality-adjusted life-years (QALYs) based on utilities translated from prospectively collected quality-of-life data. All statistical tests were two-sided.
The mean overall costs of treatment per patient in the GDP and DHAP arms were $19 961 (95% confidence interval (CI) = $17 286 to $24 565) and $34 425 (95% CI = $31 901 to $39 520), respectively, with an incremental difference in direct medical costs of $14 464 per patient in favor of GDP (P < .001). The predominant cost driver for both treatment arms was related to hospitalizations. The mean discounted quality-adjusted overall survival with GDP was 0.161 QALYs and 0.152 QALYs for DHAP (difference = 0.01 QALYs, P = .146). In probabilistic sensitivity analysis, GDP was associated with both cost savings and improved quality-adjusted outcomes compared with DHAP in 92.6% of cost-pair simulations.
GDP was associated with both lower costs and similar quality-adjusted outcomes compared with DHAP in patients with relapsed or refractory lymphoma. Considering both costs and outcomes, GDP was the dominant therapy.
The association between obesity and survival in non-Hodgkin lymphoma is unclear. Using the Ontario Cancer Registry we conducted a retrospective analysis of incident cases of aggressive-histology ...B-cell lymphoma treated with a rituximab-containing regimen with curative intent between 2008-2016. 6246 patients were included. On multivariable analysis the rate of all-cause mortality was lower for the overweight body mass index (BMI 25-29.9 kg/m
2
) (HR 0.85; 95%CI 0.77-0.95) and obese BMI (≥30 kg/m
2
) (HR 0.75; 95%CI 0.67-0.85) groups compared to the normal weight group (18.5-24.9 kg/m
2
). Binomial logistic regression analysis revealed a lower odds ratio (OR) of admission to hospital during treatment in the overweight (OR 0.84; 95%CI 0.75-0.95) compared to normal weight BMI group. In the largest cohort to date of aggressive-histology B-cell lymphoma patients treated with rituximab, increased BMI is associated with a survival advantage, and the magnitude of this effect increases from overweight to obese BMI.
The pan-Canadian Oncology Drug Review (pCODR) evaluates new cancer drugs for public funding recommendations. While pCODR's deliberative framework evaluates overall clinical benefit and includes ...considerations for exceptional circumstances, rarity of indication is not explicitly addressed. Given the high unmet need that typically accompanies these indications, we explored the impact of rarity on oncology HTA recommendations and funding decisions.
We examined pCODR submissions with final recommendations from 2012 to 2017. Incidence rates were calculated using pCODR recommendation reports and statistics from the Canadian Cancer Society. Indications were classified as rare if the incidence rate was lower than 1/100,000 diagnoses, a definition referenced by the Canadian Agency for Drugs and Technologies in Health. Each pCODR final report was examined for the funding recommendation/justification, level of supporting evidence (presence of a randomized control trial RCT), and time to funding (if applicable).
Of the ninety-six pCODR reviews examined, 16.6 percent were classified as rare indications per above criteria. While the frequency of positive funding recommendations were similar between rare and nonrare indication (78.6 vs. 75 percent), rare indications were less likely to be presented with evidence from RCT (50 vs. 90 percent). The average time to funding did not differ significantly across provinces.
Rare indications appear to be associated with weaker clinical evidence. There appears to be no association between rarity, positive funding recommendations, and time to funding. Further work will evaluate factors associated with positive recommendations and the real-world utilization of funded treatments for rare indications.
Introduction
Multiple myeloma (MM) is a malignant plasma cell disease and is considered a disease of older patients as the median age at diagnosis is 70 years. In recent years, the overall survival ...of patients with MM has improved due to the increasing number of treatment options and better supportive care. However, older patients (age >65) have not benefitted equally from the same gains. There is a paucity of information regarding clinical outcomes in this age cohort given that older patients are often under-represented in clinical trials and prospective studies. Real-world data may allows us to examine the trends in practice patterns over time and help us understand disparities in treatment options and overall patient outcomes in older patients with MM at a population level.
Methods
We conducted a retrospective population-based study using administrative data from the Institute of Clinical Evaluative Sciences (ICES), which maintains a central database of health records for all patients in the publicly funded health care system for the province of Ontario, Canada. All patients with newly-diagnosed multiple myeloma, identified using the ICD-O-3 code 9732/3 (Multiple Myeloma) between the years 2007-2017, were included to form the cohort. Autologous transplant within one year of diagnosis was captured in the database using a combination of physician billing codes and hospital procedure/discharge codes. Novel drugs usage for transplant ineligible patients was defined as the receipt of thalidomide, lenalidomide and bortezomib in any combination within one year of diagnosis. No treatment was defined as patients that did not receive a transplant, novel drugs or non-novel drugs (melphalan and cyclophosphamide) within one year following diagnosis.
Results
A total of 11,875 patients with newly-diagnosed myeloma were identified between the years 2007-2017. The proportion of newly-diagnosed MM patients who were older (age >65 years) increased from 60% of those diagnosed in 2007 to 68% of those diagnosed in 2017. The rates of autologous transplantation in older patients with MM increased from 4 to 10%. Overall those who underwent transplant had improved outcomes with decreasing one-year mortality from nearly 24% in 2007 down to 3% in 2017. Novel drugs were increasingly being used in older patients that were transplant ineligible with up to 42% receiving it within one year of diagnosis in 2017. In transplant ineligible older adults using novel drugs, one- year mortality ranged from 15% to 24%. The rates of older adults with newly-diagnosed MM not treated within one year of diagnosis was on average 49% although that number marginally declined from 54% in 2007 to 47% in 2017. Among those that did not receive treatment, 48% of individuals on average (range 40-57%) were not alive at one-year following diagnosis.
Conclusion
Our results demonstrate that although gains are being made in older adults with newly-diagnosed MM with increasing rates of transplantation and novel-drug usage over the last decade, there remains a sizeable cohort of older patients that do not receive any treatment within one year of diagnosis. While a limitation of our study may be the inclusion of some smouldering cases of myeloma, the mortality for older patients not treated continues to remain high with approximately half the patients not alive at one year following diagnosis. This study represents one of the largest cohort studies done to date over a decade demonstrating the ongoing low rates of no treatment and high rates of one-year mortality for older patients with MM. Further identification of factors associated with no treatment, transplantation and novel drug usage in older patients with MM are currently being explored.
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Mian:Amgen: Consultancy; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Pond:Roche Canada: Employment, Other: Stock; Takeda (DSMC membership): Other: Honorarium.
Bortezomib and gemcitabine have each shown activity as single agents in mantle cell lymphoma (MCL), which is incurable. The purpose of this phase II study was to determine the efficacy and safety of ...the previously unstudied combination of bortezomib and gemcitabine in patients with relapsed or refractory MCL. Patients were eligible if they had relapsed MCL with 1-3 prior therapies. Patients were treated with gemcitabine 1000 mg/m2 on days 1 and 8 and bortezomib 1.0 mg/m2 IV on days 1, 4, 8, and 11, on a 21-day schedule. Twenty-six patients were evaluable for toxicity and 25 for response. The overall response rate was 60% and the median progression free survival was 11.4 months. The main adverse effects were hematological, with 40% and 48% of patients experiencing grade 3/4 thrombocytopenia and granulocytopenia, respectively. Bortezomib and gemcitabine is an active combination in relapsed and refractory MCL with clinically meaningful results. It offers a chemotherapy backbone to which other agents, less myelosuppressive, may be added.
Abstract Purpose Anemia in cancer patients can be a result of the underlying cancer or related to treatment. Erythropoiesis-stimulating agents (ESAs) are an important option for many patients with ...chemotherapy-induced anemia, but are immersed in controversy. This article aims to reconcile conflicting opinions and provide expert guidance for appropriate ESA use. Methods Teleconference, email, and a face-to-face meeting were used to assess ESA therapy “interpretive” data, which included two current meta-analyses, expert guidelines, and regulatory approved indications from Canada, Europe, and the USA. Results Risks and benefits are associated with both red blood cell transfusions and ESA therapy, including improvements in hemoglobin levels and quality of life. ESAs have been associated with concerns regarding survival and progression of cancer, particularly when used in patients with cancer-related anemia. Conclusion Although safety concerns do exist, ESA therapy can be considered for use in patients with chemotherapy-induced anemia in accordance with Health Canada labeling.
Objectives: Cancer Care Ontario (CCO) is the provincial governmental organization responsible for planning hematopoietic cell transplantation (HCT) services in Ontario, Canada. The objective of this ...project is to develop a capacity planning model to investigate the effects on wait times of adding extra bed capacity for allogeneic transplant (ALLOHCT) in HCT centers.
Approach: A high-level process flow diagram was generated to understand patient flow at a 6-bed HCT unit within a hospital in Ontario and validated through consultation. This flow diagram was used to construct a system dynamics model to simulate patient flow. The model was parameterized with data from CCO, Discharge Abstract Database, and with hospital and clinical expert input. The effects at six months were projected for five scenarios: 1) current state; 2) increase bed capacity by 1 bed; or 3) increase bed capacity by 2 beds; 4) increasing patient demand by 20 patients per year; 5) combination of scenarios 3 and 4. Provincial clinical consensus established a benchmark wait time of 42 days for ALLOHCT from ready to transplant to the transplant date. In addition, the estimated number of beds required to reduce the wait times to the provincial benchmark within 1 year was calculated.
Results:The addition of 1 ALLOHCT bed resulted in a reduction of 22% and 11% to the ALLOHCT wait times and wait lists, respectively. The addition of 2 beds resulted in a reduction of 38% and 22% to the wait times and wait lists, respectively. If the demand increases by 20 patients per year, the addition of 2 beds resulted in a reduction of 16% in the wait times and while the wait list may experience a brief reduction, after 6 months, the wait list size will have increased by 9% as a result of the increased demand. In order to reduce the wait times to the provincial benchmark within 1 year, an additional 8 beds are needed.
Considerations: Concurrent planning for additional health human resources (physicians, nurses, etc…) needs to be done to ensure the additional beds are adequately staffed. This model also only considers the effects of adding beds within 1 year. There may be instances where bed space cannot be immediately opened and new capital is required. Additionally, the demand for ALLOHCT continues to increase, which in turn drives up the number of arrivals to the queue. A multi-year model will be built to account for timing of bed openings and increasing demand for ALLOHCT.
Conclusion:Using a system dynamics model, we are able to quantify the relationship between ALLOHCT bed capacity and wait times at an HCT center. This model can be used to estimate the ALLOHCT bed requirements for sites in other jurisdictions where ALLOHCT demand and wait time benchmarks are known.
Kouroukis:Janssen: Research Funding; Karyopharm: Research Funding.
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