Optimizing skeletal health: An analysis of bone-modifying agent prescription patterns and incidence of skeletal-related events in multiple myeloma

Abstract

Abstract Introduction Skeletal-related events (SREs) in multiple myeloma (MM) contribute to significant morbidity. Bone-modifying agents (BMAs) are recommended for every patient with newly diagnosed active MM for at least 12 months. However, in practice, this fundamental component of supportive care may not always be guideline concordant. The primary aims of this study are to investigate adherence to the International Myeloma Working Group (IMWG) guidelines for BMA use, assess delays or omissions in BMA initiation, and examine the incidence of SREs following BMA treatment. Methods We conducted a retrospective study that included newly-diagnosed and relapsed/refractory MM patients seen at two academic cancer centers between 04/28/2018 to 01/06/2025. Patients with a diagnosis other than MM and patients with MM who did not receive MM treatment or had less than 1 year of follow up were excluded. The incidence, types and locations of SREs were collected. Percentages were used to represent the proportion of patients who experienced each type and location of SRE, and therefore the sum may exceed 100%. The total number of SREs were stratified by duration of BMA use (≤ 5 years versus > 5 years), and new SREs occurring after BMA use were assessed. Time from diagnosis to BMA initiation and reason for delay were evaluated, as well as rationales for switching between different BMAs. BMA administration was then evaluated for compliance with the 2021 IMWG guideline. Results Our final analysis included 216 patients. Median age at diagnosis was 69.4 years and 50.2% were female. During the study period, 113 (52.3%) patients developed SREs, among which 86 (76.1%) had one SRE, and 111 (98.2%) had less than 4 SREs. SREs were present at baseline (within 60 days of diagnosis) in 76 patients (35.3%). Thirty-one patients (14.4%) experienced more than one type of first SREs. The most common type of first SRE was pathologic fracture (n=68, 60.2%) followed by radiation to bone (n=36, 31.9%). First SREs involved the axial skeleton in 88 patients (77.9%) and appendicular in 39 (34.5%). After the diagnosis of MM, 185 patients (85.6%) were prescribed BMA (75.1% zoledronate, 11.4% denosumab and 12.4% Pamidronate). Among these, 72 patients (39%) received BMA within 2 months. Delays in BMA initiation beyond two months after diagnosis were observed in 69 patients (37.3%), most commonly due to delayed dental clearance (n=26, 69.7%), physician decision due to absence of bone lesions (n=5, 7.2%), and patient refusal (n=7, 10.1%). One hundred and four patients (56.2%) received dental screening before BMA initiation. Seventeen patients (9.2%) switched BMA types, with suboptimal eGFR (n=6, 35.3%) being the top reason for switching. Ten patients (5.4%) developed osteonecrosis of the jaw from BMA. Thirty-three patients (17.8%) developed SREs after BMA treatment, with most events (n=11, 33.3%) between 2 and 5 years after the first dose of BMA. Relapse was observed in 38 patients (17.6%), among which 27 (71.1%) received BMA. SRE frequency was similar between BMA durations ≤ 5 years and > 5 years. Around 40% of patients had no SRE in both groups (40.3% versus 43.8%), while 48.2% of patients with BMA ≤ 5 years and 34.4% with BMA > 5 years had one SRE, respectively. Overall, 96 patients (44.4%) had BMA prescriptions that deviated from the IMWG guideline, most commonly due to delayed (n=40, 41.7%) or omitted (n=31, 32.3%) administration. Conclusion Of all BMA prescribing practices, 44.4% deviated from the guideline. The most common reason for non-compliance was delay or omission in BMA administration rather than BMA frequency or duration. Postponed dental clearance is the most common reason for the delay in BMA initiation. BMA was generally well-tolerated with around 5% of patients developing osteonecrosis of the jaw. Among patients who received BMA, 17.8% developed SREs predominantly between two to five years after the first dose, which is comparable to previous studies. Future studies may look into initiatives to improve guideline adherence.