Patients with multiple myeloma who were treated with autologous stem cell transplantation (ASCT) were found to be utilizing chronic opioids at high rates, in turn leading to worse overall survival (OS) outcomes at 6 months of follow-up,according to data from a single-center, retrospective trial presented at the 2023 Transplantation & Cellular Therapy Meetings.
“These data highlight the need to improve the understanding and management of pain in multiple myeloma and try and differentiate between cancer-related pain and chronic pain that can, perhaps, respond to other measures,” Ana Maria Avila, MD, a hematology/oncology fellow at University of Illinois at Chicago, said during a presentation of the study.
Previous illicit drug use (risk ratio [RR], 4.07; 95% CI, 1.53-10.82; P = .005) was a strong predictor of baseline chronic opioid use; meanwhile, use of known opioid analgesics (RR, 0.24; 95% CI, 0.09-0.63; P = .004), being retired (RR, 0.49; 95% CI, 0.29-0.83; P = .008), or being employed (RR, 0.37; 95% CI, 0.15-0.91; P = .031) were associated with a lower likelihood of chronic baseline opioid use. However, bony lesions (RR, 1.11; 95% CI, 0.78-1.58; P = .569) and fractures (RR, 1.01; 95% CI, 0.68-1.51; P = .963) were not associated with baseline chronic opioid use.
At ASCT discharge, median morphine milligram milliequivalent (MME) was approximately 30 mg per day, which was highest in the peri- and post-transplant setting, according to Avila. She added that, of the 80% of patients who received opioids during transplant, 60.3% were discharged on opioids. The documented reasons for being discharged on opioids were musculoskeletal (45.8%), generalized (19.3%), neuropathic (15.0%), mucositis-induced (14.5%), and headache (7.2%) pain.
Of the 36.6% of patients who became new opioid users at discharge, 15.9% were reported to chronically use opioids at 6 months post ASCT. Overall, chronic opioid use was observed in 41.4% of patients (n = 72), at a mean MME of 47.5 mg per day and median of 20 mg per day, at 6 months post ASCT. Opioid use at discharge was associated with chronic opioid use at 6 months (RR, 4.21; 95% CI, 1.46-12.11; P = .008); however, disease burden was not associated.
Following ASCT, chronic opioid use at 6 months vs no use among patients in remission led to median progression-free survival (PFS) of 39 months vs 45 months, respectively (P = .18), and median OS of 48 months vs not reached (P = .004). When adjusted for established prognostic characteristics, chronic opioid use predicted worse OS (HR, 6.71; 95% CI, 1.73-26.09; P = .006) in patients in remission following ASCT.
Chronic Opioid Use Background
Avila noted that bone pain is 1 of the most common symptoms associated with a multiple myeloma diagnosis, while skeletal-related events (SREs) can occur in 22% to 34%, leading to reduced quality of life, increased pain, and decreased survival. “So opioids are critical as an adjunctive treatment for bone pain,” she explained. “However, overuse has been associated with a significant public health crisis. Despite this, opioid use patterns have not been widely studied in this patient population.”
With prolonged periods of remission and improved survival following ASCT with maintenance therapy, the investigators aimed to describe chronic opioid use and its impact on long term outcomes, in particular, among a cohort of patients who underwent ASCT at the University of Illinois.
The single-institution, retrospective study included 174 patients aged 18 years or older who were diagnosed with multiple myeloma and underwent ASCT between January 2005 and December 2019. Information was collected from visits prior to transplant, during transplant admission, upon discharge, and at the 6- and 12-month follow-up visits after transplant.
The investigators evaluated predictors—including insurance type, educational level, employment status, alcohol use, illicit drug use, and non-opioid analgesic use—of chronic opioid use (defined as an active prescription for 3 consecutive months) at baseline and 6 months post ASCT; OS and PFS at 6 months post ASCT in patients in remission; and prognostic factors to identify predictors of OS.
The median age was 59 years (range, 29-78). In total, 51.7% of patients were male, and the majority were Black (60%). Further, 63.8% of patients had International Myeloma Working Group-defined bone disease, 26% experienced a myeloma-related fracture, 27.6% were high-risk fluorescence in situ hybridization/karyotype, and 31% had stage III disease.
Among treatment-related characteristics at baseline, 83% received a proteasome inhibitor, an immunomodulatory agent, or an anti-CD38 monoclonal antibody. Further, 71% of patients received post-transplant maintenance therapy.
Among 174 patients, chronic opioid use was observed in 92 (52.9%) at baseline, including 27 (29.3%) who had no prior history of bone disease. The baseline MME was 65.3 mg per day. Of note, 20 mg or more per day correlates with a risk for overdose events, Avila said.
Strengths and Limitations
Avila noted that the study was limited by its single-center, retrospective analysis design, “so findings might not be generalizable.” Additionally, she said there was no correlation with the Illinois Monitoring Prescription Program, which could have accounted for additional opioid prescriptions.
However, Avila highlighted the study’s strengths, including “the description of opioid use patterns in a myeloma population that is ethnically diverse and is usually underrepresented in myeloma studies; and, in particular, would describe opioid use patterns in long-term survivors.”
Avila concluded that next steps should include the identification of potential barriers to opioid discontinuation in larger, collaborative databases, and the validation of clinical opioid predictive tools in the peri-transplant setting. “And hopefully [we] have larger prospective trials evaluating alternative opioid-sparing strategies in patients with myeloma in the peri- and post-transplant setting,” she concluded.
Avila Rodriguez A, Quigley J, Sweiss J, et al. Chronic opioid use is highly prevalent and associated with inferior survival in myeloma patients in remission after autologous transplant. Presented at: 2023 Transplantation & Cellular Therapy Meetings; February 15-19, 2023; Orlando, FL. Abstract 51.