Despite Therapeutic Developments in MM, Refractory Patients Face Poor Prognosis: Study

Patients with multiple myeloma (MM) face a poor prognosis following relapse to multiple different lines of therapy (LOTs) and triple-class exposure (TCE), and exhibit worsening survival outcomes, new research published in the European Journal of Haematology found.

Authors of the retrospective observational cohort study, which was carried out in France, also noted access to novel therapies may improve outcomes for these patients. France has the second-highest incidence of MM in the European Union, while a large proportion of elderly patients are ineligible for transplants, underscoring the need to identify treatment patterns that offer the best potential survival.

The treatment landscape for MM has rapidly evolved in recent years thanks to the introduction of new therapies like proteasome inhibitors (PIs), immunomodulatory drugs, and CD38-targeting monoclonal antibodies (mAbs).

However, despite these developments, study results show “standard of care has not been established for patients whose disease are relapsed or refractory to multiple treatments, particularly triple-class exposure, in whom outcomes and survival are suboptimal,” researchers explained.

In an effort to better understand the overall survival (OS) of patients with MM at different treatment stages, investigators assessed administrative claims data recorded in the French National Healthcare database. All patients were diagnosed between 2013 and 2017.

A total of 14,309 patients were included in the final analysis. All patients had received at least 1 MM-specific treatment. Median patient age at diagnosis was 71, while nearly 60% of patients were between the ages 65 and 85 at diagnosis.

The most common comorbidities were diabetes, chronic lung disease, and moderate or severe kidney disease.

Data showed:

• From diagnosis, death rates increased from 1% at 1 month to 24% at 2 years; median OS was 63.8 months
• Median OS from the start of LOTs declined from 61.0 months (LOT1) to 14.8 months (LOT4)
• Median OS from TCE start was 14.7 months
• There was a large variation in time-to-next-treatment (TTNT) within LOTs (eg, LOT1: bortezomib + lenalidomide: TTNT = 26.4 months, OS = 61.7 months; lenalidomide: TTNT = 20.0 months, OS = 39.6 months)
• Duration of therapy was similar for LOT1 and LOT2, then progressively declined at LOT4
• Patients with stem cell transplant, younger age, and less comorbidity had better survival outcomes

In addition, results showed the most frequently used treatment regime for each LOT didn’t always lead to the optimal median OS or longest median TTNT, authors wrote.

“In most instances, less frequently used treatment regimens produced longer TTNT and OS, suggesting improved disease symptom control with perhaps better tolerability,” they added.

It may take newer treatment approaches longer to be incorporated into the treatment landscape, researchers explained. This could be why fewer patients were exposed to some regiments with better OS and TTNT in earlier line settings.

Furthermore, older patients may have poorer survival outcomes due to increased treatment-related toxicity and lower tolerability to MM therapies.

The administrative claims data used in the current analysis may under- or misreport outcomes, marking a limitation to the study. Alkylating agents like melphalan and cyclophosphamide were also not included in the study to define LOTs.

Follow-up was only carried out until the end of 2019, meaning newer treatments for the disease may not have been included in the data.

“The recent entry of novel treatment options such as chimeric antigen receptor (CAR) T-cell therapy may offer important new treatment options that may further improve outcomes in this difficult to treat patient population,” authors wrote.

Overall, results showed that despite developments for MM therapeutic strategies, once the disease becomes refractory to multiple treatments, patients face a “very poor prognosis,” researchers concluded.

Reference

Leleu X, Gorsh B, Bessou et al. Survival outcomes for patients with multiple myeloma in France: A retrospective cohort study using the Système National des Données de Santé national healthcare database. Eur J Haematol. Published online May 18, 2023. doi:10.1111/ejh.13976