# Impact of treatment delay of multiple myeloma bone disease on later myeloma-related skeletal events and outcome

## TL;DR

Delaying treatment for multiple myeloma bone disease increases the risk of later fractures and worsens patient outcomes.

## Contribution

This study provides real-world evidence that treatment delays in bone disease correlate with increased skeletal events and poorer survival in multiple myeloma patients.

## Key findings

- Tooth extraction at diagnosis increases the risk of osteonecrosis of the jaw.
- Delayed bone disease treatment predicts earlier and more frequent later fractures.
- Denosumab treatment is associated with poorer overall survival and earlier fractures.

## Abstract

•A real-world data with detailed information on MM patients’ dental care.•The main reason for a delay was tooth extraction.•Tooth extraction at diagnosis stage increases the risk for ONJ.•A treatment delay in bone disease may predict earlier and frequent later fractures.•Fracture and bone disease at diagnosis predict earlier later fractures.

A real-world data with detailed information on MM patients’ dental care.

The main reason for a delay was tooth extraction.

Tooth extraction at diagnosis stage increases the risk for ONJ.

A treatment delay in bone disease may predict earlier and frequent later fractures.

Fracture and bone disease at diagnosis predict earlier later fractures.

Limited data exists on the effect of treatment delay of multiple myeloma (MM) bone disease on the disease course. In this real-world analysis of 625 patients with newly diagnosed MM (NDMM) we aimed to investigate the impact of delay in starting bone disease treatment on later skeletal events and outcome.

Altogether 480 (76.8 %) patients had bone disease at the diagnosis, 282 (45.1 %) patients had a fracture at diagnosis, and 181 (29.1 %) patients had a later fracture during the follow-up. A delay in the initiation of treatment of bone disease was experienced by 221 (35.4 %) patients and tooth extraction was a main reason for the delay. Patients with a delay seemed to experience earlier and more frequent later fractures. Also, a fracture (p = 0.003) or bone disease (p < 0.001) at diagnosis predicted earlier incidence of later fractures. As a bone targeted treatment, altogether 363 (58.1 %) patients received zoledronic acid, 81 (13.0 %) denosumab and 134 (21.4 %) other bone-targeted treatment. Patients treated with denosumab had poorer overall survival (OS) (p < 0.001) and experienced earlier later fractures (p = 0.003). Multivariate analysis showed that bone disease at diagnosis (p = 0.043) and given bone disease treatment (p = 0.023) significantly impacted on the time to next fracture. Regarding OS, delay in osteoprotective treatment (p = 0.004) and time of the diagnosis (p < 0.001) were significant factors in multivariate analysis.

To conclude, this study suggests that early initiation of bone disease treatment seemed to prevent later fractures. These findings highlight the importance of patients’ rapid access to a dentist and the start of bone targeted treatment without delay after a myeloma diagnosis.