Chronic opioid use following auto-HSCT in patients with MM

Pain is a common symptom experienced by patients with multiple myeloma (MM), with opioids often prescribed as a pain management strategy. While opioids may be an integral part of pain management, opioid overuse has been associated with a significant public health crisis.¹ The effect of chronic opioid use (COU) on outcomes in patients with MM has become an important area of investigation. The Multiple Myeloma Hub has previously held a symposium on pain management for patients with MM.

During the 2023 Transplantation & Cellular Therapy Meetings of the ASTCT and CIMBTR, Rodriguez presented results from a retrospective analysis on the prevalence and effect on outcomes of COU following autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with MM, which we are pleased to summarize below.¹

Study design and patient characteristics

This retrospective analysis aimed to describe the instances of COU, defined as a documented active prescription for 3 consecutive months, and the impact on long-term survival outcomes in 174 patients with MM aged ≥18 years old who underwent auto-HSCT from 2005 to 2019 at the University of Illinois Chicago, US. Overall survival (OS) and progression-free survival (PFS) were assessed at 6 months post-auto-HSCT. Daily opioid doses were converted to morphine milligram milliequivalents (MME). The median age in this study was 59 years (Table 1).

Table 1. Baseline patient characteristics*

Auto-HSCT, autologous hematopoietic stem cell transplantation; FISH, fluorescence in situ hybridization; IgA, immunoglobulin A; IgG, immunoglobulin G; IMWG, International Myeloma Working Group; ISS, International Staging System. *Adapted from Rodriguez.1
Characteristics, % (unless otherwise specified)	N = 174
Median age (range), year	59 (29–78)
Gender
Male	51.7
Race
White	13.2
Black	60.3
Hispanic	13.8
Received novel agent-based induction	83.3
Median time to auto-HSCT (range), months	7 (1–144)
Median number of prior lines of therapy(range), n	1 (1–5)
Received post-auto-HSCT maintenance	71.0
IMWG-defined bone disease	63.8
Paraprotein subtype
IgG	60.9
IgA	19.0
Light chain	20.1
High-risk FISH/karyotype
Yes	27.6
No or unknown	72.4
ISS stage
1	20.1
2	25.9
3	31.0

Key findings

• At baseline, COU was observed in 52.9% of patients, of which 29.3% did not have a prior history of bone disease (Table 2).
• The baseline average MME per day was 65.3 mg (±70.0; Table 2)
  • MME ≥20 mg/day has been associated with a higher risk for overdose events.

Table 2. COU rates and average MME per day*

COU, chronic opioid use; MME, morphine milligram milliequivalents. *Adapted from Rodriguez.1
Rates	Patients with bone disease	Patients without bone disease	p value
COU rates, %	52.4	54	0.98
Average MME/day, mg	69.5	55.2	0.37

Based on multivariable modified Poisson regression models, previous illicit drug use was associated with baseline opioid use, while the use of non-opioid analgesics, being retired, or being employed had a negative correlation (Table 3).

Table 3. Multivariable modified Poisson regression model of association with baseline opioid use*

CI, confidence interval; RR, relative risk. *Adapted from Rodriguez.1
Variable	RR	95% CI	p value
Previous illicit drug use	4.07	1.53–10.82	0.005
Use of non-opioid analgesics	0.24	0.09–0.63	0.004
Retired	0.49	0.29–0.83	0.008
Employed	0.37	0.15–0.91	0.031
Bony lesions	1.11	0.78–1.58	0.569
Fractures	1.01	0.68–1.51	0.963

• 81.6% of patients received opioids during auto-HSCT admission and 60.3% received an opioids prescription at discharge.
  • The documented reasons for opioid prescription at discharge included musculoskeletal pain (45.8%), generalized pain (19.3%), neuropathic pain (15%), mucositis-induced pain (14.5%), and headaches (7.2%).
• Among baseline non-opioid users, 36.6% were new opioid users at discharge, of which 15.9% met the criteria for COU at 6 months.
• Opioid use at discharge was associated with COU at 6 months (relative risk, 4.21; 95% confidence interval [CI], 1.46–12.11; p = 0.008).
• Indicators of disease burden, including bone lesions, were not associated with COU at 6 months.
• In univariate analysis, COU at 6 months post-auto-HSCT was not associated with median PFS compared with no COU (39 months versus 45 months; p = 0.18).
• However, COU at 6 months post-auto-HSCT was associated with inferior median OS compared with no COU (48 months versus not reached; p = 0.004).
• In the multivariable model, COU at 6 months predicted worse OS (hazard ratio, 6.71; 95% CI, 1.73–26.09; p = 0.006) when adjusted for established prognostic characteristics.

Conclusion

In this retrospective analysis, high rates of baseline COU unrelated to bone disease were observed. High rates of opiate use at discharge including new users were noted, leading to COU at 6 months post-auto-HSCT in patients with MM. Patients who met the criteria for COU at 6 months post-auto-HSCT had inferior OS but not PFS, suggesting that opioid-related morbidity may impact patient outcomes.

While this study is limited by its single-center, retrospective nature, the results warrant further prospective investigation to improve the understanding of pain management in patients with MM. Alternative pain management strategies may prove beneficial in this patient population.