Population-level survival of patients with multiple myeloma (MM) has been improving significantly for decades, causally attributable to, among others, the introduction of novel agents and autologous stem cell transplantation (SCT). Nonetheless, early mortality (EM) remains a major clinical issue, especially in older patients. To date, prospective studies have reported on EM among patients with MM, thereby applying various definitions of EM, mainly using cut-off marks of 60 or 180 days. Moreover, single- and multi-center studies, often performed in large academic hospitals, probably underestimate the proportion of patients with EM, as many elderly and frail patients are infrequently referred to a specialized myeloma center.
As a researcher working with data available in the Netherlands Cancer Registry (NCR), I had the opportunity to explore the aspects of EM in MM patients, in collaboration with hematologists from various hospitals in the Netherlands. The NCR, maintained and hosted by the Netherlands Comprehensive Cancer Organisation (IKNL), is unique as all patients seen in routine clinical practice are captured.
Netherlands Cancer Registry
The population-based NCR has nationwide coverage of at least 95% of all malignancies since 1989. The NCR relies on comprehensive case notification through the Nationwide Histopathology and Cytopathology Data Network and the Nationwide Registry of Hospital Discharges (i.e. inpatient and outpatient discharges). Information on dates of birth and diagnosis, sex, topography and morphology, hospital type of diagnosis, and first-line therapy is routinely recorded in the NCR by trained registrars of the NCR through retrospective medical records review in the Dutch hospitals. Information on last known vital status for all patients (i.e. alive, dead, or emigration) is obtained through annual linkage with the Nationwide Population Registries Network that holds vital statistics on all residents of the Netherlands. Since January 1st, 2014, detailed information on diagnostic and treatment characteristics for all hematological malignancies diagnosed in the Netherlands is routinely recorded.
Randomized clinical trials (RCTs) are considered the gold standard for establishing efficacy of new therapies. However, RCTs have strict inclusion criteria for participation, thereby usually excluding elderly and frail patients on forehand. As a consequence, generalizability of the outcomes in routine practice is jeopardized. The observational nature of population-based studies contributes to better generalizability, as all patients are included and treatment decisions are based on clinical and patient preferences. Thus, population-based studies provide a unique insight into everyday clinical practice. The NCR allows the evaluation of outcomes in the general patient population and provides information regarding use of treatment and outcomes in a real world setting. Especially for groups of patients who do not meet the eligibility criteria from RCTs, observational studies are of utmost importance.
Regarding our study, the NCR was an important tool to gain more insight into risk factors for and trends of EM among patients with multiple myeloma. It is important to carefully weigh the risk of EM in individual patients at diagnosis, as this may help clinicians in decision-making treatment options for MM patients at risk of EM. Moreover, our results report on the state-of-art of where we stand in the Netherlands regarding improvements of survival and may decline uncertainties regarding optimal treatment, thereby reducing variation in care. Finally, our results are essential to establish recommendations for better supportive care or individualized, less toxic, anti-MM therapies, to further reduce EM in this patient population.
In summary, using the NCR, understanding the determinants of EM may translate into handles for clinicians to recognize risk on EM and to adapt daily care practice, in particular supportive care and individualized treatment strategies, for patients at risk.