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Management of pain: Understanding the current needs of patients with multiple myeloma

Mar 31, 2022
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Disclaimer: All content produced by the Multiple Myeloma Hub is intended to adhere to the  Centers for Disease Control and Prevention Guideline for Prescribing Opioids for Chronic Pain, issued in March 2016. Opioids are a class of highly addictive prescription painkillers; therefore, it is crucial all information regarding their use is accurate in describing the benefits but also serious risks. Key principles to be taken into consideration include (i) nonopioid therapy is preferred for chronic pain outside of active cancer, palliative, and end-of-life care; (ii) when opioids are used, the lowest possible effective dosage should be prescribed to reduce risks of opioid use disorder and overdose; and (iii) clinicians should always exercise caution when prescribing opioids and monitor all patients closely. 

Pain is a commonly experienced symptom in patients with multiple myeloma (MM), contributing to poor health-related quality of life. Although pain management is an integral part of cancer care, it is often undertreated, or the treatment is not proportional to pain intensity. Reasons for undertreatment include lack of knowledge and understanding of pain, patients’ reluctance to accept pain, and healthcare professionals’ failure to understand the impact of pain on patients’ life, leading to poor communication.1

Patients with MM experience chronic pain, with up to 90% of patients experiencing bone pain from osteolytic bone lesions. Different types of pain (bone pain, pain from chemotherapy-induced peripheral neuropathy, somatic pain, and chronic pain) may be experienced at different stages of MM, and each type of pain requires careful assessment of symptoms to identify the most effective treatment.2 The management of bone pain in patients with MM frequently involves the administration of opioids; while these are effective for moderate to severe pain, their long-term use may lead to numerous mental and physical health problems, including an increased risk of depression. Opioid-related deaths are increasing in patients with cancer due to higher levels of chronic pain and long-term opioid therapy. Survivors of cancer are at an increased risk of non-medical opioid use (without prescription) and opioid use disorders.3 Other issues, such as cumulative toxicities from multiple lines of therapy, and physical, psychological, and social aspects of MM, also need to be considered along with a holistic approach to pain management in MM.2

Autologous hematopoietic stem cell transplantation (auto-HSCT) and myeloma-directed therapies have radically improved treatment responses, disease control, and survival. In addition, recent improvements in supportive care, including bisphosphonates and nuclear factor kappa B ligand inhibitor, have decreased the reliance on opioids. As patients with MM are surviving longer, exploring if these patients can decrease and discontinue pain medication is needed, as is identifying potential barriers to opioid withdrawal. Currently, there is a lack of evidence on different aspects of pain experienced by patients with MM. Here, we present the key findings from a retrospective study by Danish et al.4 recently published in the European Journal of Haematology, examining the prevalence of opioid use and change in opioid dose as a function of response to therapy in patients with MM who have received induction therapy and auto-HSCT.

Study design

This was a retrospective cohort study of patients with MM who received auto-HSCT between January 2012 and December 2017 and had subsequent follow-up (at 100 days and 1 year). Only patients who had adequate post-transplant follow-up of at least 1 year were included. Response was defined according to the International Myeloma Working Group (IMWG), and each response was grouped into three broad groups to accurately reflect clinical response regarding opioid use (Table 1).

  • The primary outcome was the status of opioid use at 1 year post auto-HSCT.
    • Escalated, stable, or de-escalated opioid use was based on the dose of opioids administered at the time of transplant (Figure 1).

Table 1. Response definitions and categories*

Response category

Criteria

Group 1: Good responders

CR and VGPR

Group 2: Partial responders

PR and SD

Group 3: Non-responders

PD and those who show PD after initial response

CR, complete response; PD, progressive disease; PR, partial response; SD, stable disease; VGPR, very good partial response.

 *Data from Danish, et al.4

 Figure 1. Opioid use status and changes in opioid dose post auto-HSCT*

Auto-HSCT, autologous hematopoietic stem cell transplantation.

*Data from Danish, et al.4

Results

Baseline characteristics

A total of 138 patients were followed up for at least 1 year; with a median age of 58.7 years (range 3575 years) and a male/female ratio of 55.1%/44.9%.

In total, 52 patients were treated with opioids at the time of auto-HSCT, and younger age was associated with increased use of opioids (p = 0.0115).

  • Neuropathy and presence of bone lesions were also common in the group treated with opioids (p = 0.01772 and p = 0.0011, respectively) (Table 2).

Table 2. Baseline characteristics*

Characteristics, % (unless otherwise stated)

All
(N = 138)

Patients not treated with opioids
(n = 86)

Patients treated with opioids
(n = 52)

p value

Age, years

 

 

 

 

              <40

1.4

0.0

3.8

              4049

12.3

7.0

21.2

              5059

38.4

36.0

42.3

              6069

34.8

41.9

23.1

              7079

13.0

15.1

9.6

              Mean (SD)

58.7 (8.8)

60.4 (8.1)

55.9 (9.2)

0.0034

Symptoms at presentation

 

 

 

 

              Neuropathy

68.1

64.0

75.0

0.1772

              Bony lesions

71.6

62.8

87.0

0.0011

Comorbidities

 

 

 

 

              HTN

47.1

47.7

46.2

0.8623

              HLD

29.0

34.9

19.2

0.0495

              VTE

18.8

18.6

19.2

0.9274

              Type 2 DM

15.2

15.1

15.4

0.9661

              Depression/anxiety

10.1

11.6

7.7

0.4581

              CAD

8.7

11.6

3.8

0.1159

              Osteoporosis

9.4

11.6

5.8

0.2536

              Other cancer

7.2

9.3

3.8

0.2309

              OA/DJD

8.7

10.5

5.8

0.3428

              Shingles

8.7

10.5

5.8

0.3428

              CHF

2.2

3.5

0.0

0.1733

              Gout

2.9

3.5

1.9

0.5953

              Substance abuse

3.6

2.3

5.8

0.2942

              Asthma/COPD

5.8

3.5

9.6

0.1356

CAD, coronary artery disease; CHF, congestive heart failure; COPD, chronic obstructive pulmonary disease; DJD, degenerative joint disease; DM, diabetes mellitus; HLD, hyperlipidemia; HTN, hypertension; OA, osteoarthritis; SD, standard deviation; VTE, venous thromboembolism.
*Adapted from Danish, et al.4
Values in bold are statistically significant.

Responses

The response status of patients was recorded at three timepoints; at auto-HSCT, 100 days post auto-HSCT, and 1-year post auto-HSCT, as shown in Figure 2.

Figure 2. Response statuses at the time of and post auto-HSCT*

Auto-HSCT, autologous hematopoietic stem cell transplantation; CR, complete response; PD, progressive disease; PR, partial response; Re, reappearance of M protein and/or >5% plasma cells in the bone marrow and/or new CRAB features; SD, stable disease; VGPR, very good partial response.
*Data from Danish et al.4

Opioid use

Overall, there was a decline in the percentage of patients treated with opioids at auto-HSCT (37.7%), 100 days (36.2%), and 1 year (31.9%); however, the change was only statistically borderline significant (p = 0.0809) (Table 3).

  • Opioid use was statistically significant at 1 year compared with at the time of auto-HSCT (Table 3).
  • Although ~62.3% of patients achieved at least a very good partial response, 75% of patients treated with opioids either continued or increased their dose at 1 year post auto-HSCT.

Table 3. Comparison for opioid use in disease response and time*

Pairwise comparison

OR (95% CI)

p value

Non-responders vs partial responders§

0.89 (0.36–2.21)

0.8059

Non-responders vs good responders

0.66 (0.27–1.61)

0.3631

Partial responders§ vs good responders

0.74 (0.49–1.13)

0.1624

1 year vs 100 day

0.83 (0.65–1.06)

0.1400

1 year vs at auto-HSCT

0.75 (0.57–0.98)

0.0376

100 day vs at auto-HSCT

0.90 (0.68–1.18)

0.4433

Auto-HSCT, autologous hematopoietic stem cell transplantation; CI, confidence interval; OR, odds ratio.
*Adapted from Danish, et al.4
Values in bold are statistically significant.
Non-responders = progressive disease and relapse from complete remission.
§
Partial responders = stable disease.
Good responder = complete response and very good partial response.

Assuming an 82 morphine equivalent in millimeters per day (ME/day) was approximately 11 tablets of oxycodone 5 mg/day, the mean use amongst patients who continued to use opioids for the entire study period was:

  • 79.4 ME/day at time of auto-HSCT
  • 79.1 ME/day at 100 days post auto-HSCT
  • 88.7 ME/day at 1 year post auto-HSCT

Conclusion

This retrospective analysis demonstrated that the pain burden and use of opioids in patients with MM remained high despite excellent response rates in most patients. Symptomatic neuropathy was common in both individuals treated with and not treated with opioids, and as neuropathic symptoms remain poorly managed, minimizing neuropathic medication might be an optimal pain management approach. In addition, long-term opioids have little effect in managing chronic non-malignant pain. Rather, long-term use of opioids may increase the sensitivity to pain, leading to further opioid dose escalation and dependence, highlighting the need to distinguish cancer-related and chronic non-malignant pain.

The persistently high level of opioid use could either represent continued pain or an over and undesirable consumption of opioids in this population. However, the generalizability of the study findings is limited due to being a single center, retrospective study, including a relatively small number of patients, a lack of precise measurement of opioid dosing and frequency, and a lack of assessment of severity and quality of pain. Despite the study’s limitations, this was the first study to examine opioid use in patients with MM, warranting further research into strategies to reduce medication-induced neuropathic pain and continuously assess the need for pain management strategies to be used in this population.

  1. Quinn B, Ludwig H, Bailey A, et al. Physical, emotional and social pain communication by patients diagnosed and living with multiple myeloma. Pain Manag. 2022;12(1):59-74. DOI: 2217/pmt-2021-0013
  2. Pallotti MC, Rossi R, Scarpi E, et al. Patients with multiple myeloma referred for palliative care consultation: from retrospective analysis to future directions to improve clinical outcomes. Support Care Cancer. 2022;30(3):2293-2298. DOI: 1007/s00520-021-06560-8
  3. Bates N, Bello JK, Osazuwa-Peters N, et al. Depression and long-term prescription opioid use and opioid use disorder: implications for pain management in cancer. Curr Treat Options Oncol. 2022;23(3):348-358. DOI: 1007/s11864-022-00954-4
  4. Danish ML, Shah MR, Lin Y, et al. Persistent opioid use in patients with multiple myeloma post-ASCT. Eur J Haematol. 2022. Online ahead of print. DOI: 1111/ejh.13759