Long-Term Follow-Up of Multiple Myeloma (MM) Patients (pts) with Osteonecrosis of the Jaw (ONJ).
Authors: Badros Ashraf , Evangelos T. , Goloubeva O. , Meiller T. , Kastritis E. , Verrou E. , Zervas K. , Katodritou E. , Streeten E. , Baer M.R. , Dimopoulos M.A. 
Published: October 2019

Abstract
Risk factors for ONJ in MM pts include dental extraction, bisphosphonates (BP) use, older age and longer survival. There is also an increased risk of skeletal related events (SRE) in ONJ pts (Badros, JCO 2006). The current study provides long term follow-up data for ONJ pts with regard to ONJ recurrence, SRE and MM status. The study included 97 pts: 60 from Greece and 37 from the US. Pts’ characteristics are summarized in the table below. Median follow-up time has not been reached; lower limit of the 95%CI was 3.2 yrs. ONJ resolved in 60 of 97 pts (62%), resolved and recurred in 12 pts (12%), and did not heal over a 9 months period in 25 pts (26%). Dental extraction preceded ONJ in 46 of 97 pts (47%) and was more common in pts with a single episode of ONJ (35 of 60, 58%) than in the recurrent and non-healing pts (11 of 37, 30%) (p-value=0.007). The median number of ONJ episodes in the recurrent group was 3 (range, 2–6); recurrence of ONJ was precipitated by re-initiation of BP and by dental procedures in 5 and 4 pts of 12, respectively. There was a trend toward higher ONJ recurrence rate in the US (8 of 37, 22%) versus the Greek (4 out of 60, 7%) pts (p-value=0.053). Surgery was performed more often in the US than in Greece 17 of 37 (45%) versus 19 of 60 pts (32%). BP reinitiation was more frequent in US 16 of 37 (43%) than in Greece 3 of 60 (5%). Non-healing ONJ lesions were managed with antibiotics; 10 of 25 pts developed fistulas and needed surgery; in 9 pts the lesions remained asymptomatic. Twenty-one ONJ pts had SRE including fractures (ribs, vertebrae and long bones, n=13) and avascular necrosis of the femur (n=8). The rate of MM relapse was higher in pts with recurrent and non-healing ONJ (84%) compared to pts with a single episode (62%) (p-value=0.02). The median OS from diagnosis of MM was 10.8 yrs (95% CI; 9.3 yrs- not reached) and did not differ between pts with single, recurrent/non-healing ONJ (p= 0.2). In summary, pts in whom ONJ followed dental procedures were less likely to have recurrence or non-healing, both, although infrequent, were linked to BP re-challenge, mostly in the setting of relapsed MM. Non-healing ONJ lesions remained stable/asymptomatic without extensive intervention. BP should be discontinuation until ONJ lesions heal. The decision to restart BP should be individualized based on MM-SRE risk.
ONJ Pts characteristics and outcome AA, African American; ttt, treatment; CR, complete remission; PR, partial remission; PD, progressive disease; Dex, dexamethasone, thal, thalidomide; Len, lenalidomide; Bort, bortezomib; A, pamidronate; Z zoledronic acid. The Fisher’s Exact test was used, all p-values reported are two-sided. ONJ, n= 97 one episode, n=60 recurrent, n=12 non-healing, n=25 age at MM; median (range) 60 (26–77) 61 (26–77) 55 (43–76) 61 (36–73) Sex; male/female 59/38 38/22 8/4 13/12 Caucasian/AA 87/10 54/6 10/2 23/2 Isotype; IgG, A, D, LCH 60/20/1/16 36/11/1/12 7/2/0/3 17/7/0/1 MM ttt at ONJ (n=93); none/dex/thal/len/bort 22/31/26/6/8 11/25/16/4/2 5/1/3/1/1 6/5/7/1/4 MM status at ONJ diagnosis; CR/PR/PD 7/54/33 4/37/17 3/8/1 0/9/15 BP use; AZ/Z 59/35 34/23 10/2 15/10 Dental extraction 46 35 5 5 Restarted BP 19 11 6 2 bone complciations 21 14 3 4 MM course after ONJ; continous remission/Relapse 29/68 23/37 2/10 4/21 MM status at last follow up; CR/PR/PD (died) 3/59/35(28) 3/35/22(20) 0/10/2(2) 0/14/11(6)