Analysis Identifies International Treatment Outcomes, Patterns in Individuals With NDMM

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The authors found that overall survival in patients with newly diagnosed multiple myeloma was longest for those receiving first-line autologous stem cell transplantation.

Key Takeaways:

  1. Treatment Disparities Across Countries: Variations in the time from multiple myeloma (MM) diagnosis to treatment initiation highlight potential differences in health care systems' efficiency and patient management strategies. Additionally, the preference for bortezomib (BTZ)-based regimens in Denmark and Finland over Sweden suggests varying clinical practices or drug accessibility among these nations.
  2. Persistence and Time to Next Treatment (TTNT): High treatment persistence with melphalan-prednisolone-thalidomide underscores its potential as a well-tolerated regimen, possibly contributing to better long-term outcomes. Alternatively, shorter TTNT observed with BTZ may indicate the need for more effective following therapies or the emergence of drug resistance.
  3. Overall Survival (OS) and Treatment Outcomes: The longer OS observed in autologous stem cell transplantation patients emphasizes the importance of this intervention in improving survival prospects for MM patients. Further, the wider variability in survival outcomes associated with lenalidomide-based regimens suggests the need for better patient stratification or treatment optimization to maximize therapeutic benefits.

Survival rates in patients with multiple myeloma (MM) have improved in recent years due to the introduction of new drugs and changes made in treatment strategies; however, MM remains incurable, with survival rates varying across countries. In particular, patients with newly diagnosed MM (NDMM) can relapse and become refractory to treatment, resulting in drug resistance. Using the large-scale, retrospective Health outcomes and Understanding of MyelomA multi-National Study (HUMANS), investigators analyzed the treatment patterns, clinical outcomes, and characteristics of patients with NDMM from 2010 to 2018.

Patients who were first diagnosed with MM between January 2010 and December 2016 who initiated first-line (1L) therapy specifically to treat MM were included in the study. Study participants were from Denmark, Finland, and Sweden, and patients who had other hematological cancers or received MM-specific treatment prior to their MM diagnosis were excluded from the analysis. Depending on the 1L MM-specific therapy they received, patients were placed into either the autologous stem cell transplantation (ASCT) group or non-ASCT group (combination therapy).

Stem cell research -- Image credit: luchschenF | stock.adobe.com

Image credit: luchschenF | stock.adobe.com

Further, index treatment was defined as MM-specific 1L therapy, and index therapy was defined as the initiation of treatment and classified as either ASCT or a combination therapy depending on the regimen that was used. In the event that dispensing dates for drugs in combination therapies were different, the earliest treatment was considered the initiation date. The study authors note that a treatment arm in Denmark—melphalan-prednisolone-thalidomide (MPT)—was excluded because of inconsistencies when reporting for patients who received this 1L treatment.

The authors defined treatment persistence as the number of days/months in which a treatment was taken—from first dose/first day to the last day of the last dispensed dose or discontinuation—with a grace period of 60 days. In addition, a treatment break was recorded if a patient had not been dispensed treatment for a given time but continued with the same treatment. For patients from Denmark, dispensed package or dose information was unavailable, so a defined daily dose (DDD)—defined as the number of days after the last dispensation—was used. The authors note that 28 days was assumed for lenalidomide (LEN) and 7 for bortezomib (BTZ). Additionally, overall survival (OS) was evaluated and calculated from MM diagnosis to death, and from initiation of 1L therapy to death. Time to next treatment (TTNT) was defined as the time from initiation of 1L to that of 2L treatment.

A total of 25,326 patients were identified across Denmark, Finland, and Sweden, of which 11,023 (43.5%) were treated during the study’s duration. Of the patients treated, approximately 33.3% received ASCT as a 1L treatment (n = 2924). According to the analysis, patients who underwent ASCT had a younger median age (60-61 years) compared to those who received BTZ or LEN (70-74 years). Further, patients who received different chemotherapy regimens in the 1L setting were older at diagnosis (median: 75-77 years) and at treatment initiation (median: 76-78 years) than those who were treated with BTZ or LEN in the 1L setting.

The study also indicated that the time between diagnosis and treatment varied in different countries, with Denmark having the shortest amount of time between diagnosis and treatment (0.9 months), and Finland having the longest (4.6 months). In addition, BTZ-based treatment regimens were more frequently prescribed as a 1L treatment in Denmark and Finland, with approximately 50% of patients receiving this treatment, whereas in Sweden, only 21% of patients received BTZ-based regimens in the 1L setting. The analysis also demonstrated that patients who received 1L LEN had to wait the longest for treatment (Denmark: 3.2 months; Finland 8.1 months; Sweden: 12.1 months), whereas those receiving MPT-based regimens were treated within 2 months.

Because of limitations with drug registration, treatment persistence could not be determined for MPT in Denmark and BTZ in Sweden. Further, treatment persistence was shown to be the highest among those treated with MPT in Finland (8.1 months) and Sweden (7.4 months). The lowest persistence was among those who received 1L BTZ compared with MPT and LEN, with persistence in Finland being shorter with BTZ (3.5 months) than with MPT (8.1 months).

Because of 2L treatment being administered primarily in the hospital setting, the TTNT analysis was only conducted in Denmark. For patients treated with BTZ, TTNT was shorter (15.3 months) than for those treated with LEN (16.9 months). Further, there was a high degree of variability for the 2 OS timeframes regardless of treatment; however, OS across the 3 countries from diagnosis was the longest for patients who underwent ASCT (main analysis: 93-117 months; sensitivity analysis: 72-99 months).

In addition, the authors note that patients who had received LEN regimens were more likely to survive than those who received BTZ treatments; however, there was more variability in OS during both timeframes among patients receiving LEN (62-78 months) than those receiving BTZ (53-58 months).

The authors note some limitations with the data sources examined in the study, including the inability to evaluate all patient characteristics at baseline (eg, disease stage, risk status); the lack of disease-specific outcomes that were collected (eg, progression-free survival); and the variation of registration methods, diagnostic habits, and procedure codes across the 3 countries. Further, the authors note that the data may not be applicable in other countries due to differences in clinical practices or health care systems.

Reference

Abildgaard N, Anttila P, Waage A, et al. Real-world treatment patterns and outcomes for patients with multiple myeloma in Denmark, Finland and Sweden: An analysis using linked Nordic registries. Eur J Cancer. 2024;201:113921. doi:10.1016/j.ejca.2024.113921

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