Buprenorphine as an Alternative for Pain Management in Bone Marrow Transplants

Mayuko Sakae, MD

Bone marrow transplants (BMT) offer a potential cure for various cancers and incurable diseases. However, this approach often brings about multisystemic pain and management challenges for patients with pre-existing conditions and baseline hypersensitivity to pain.

For some patients, including those with sickle cell disease, chronic pain and opioid use are dealt with from an early age and often leads to severe pain during BMT. Traditional opioids have struggled to manage this escalating pain effectively, resulting in significant increases in opioid doses and associated adverse effects (AEs).

A recent study evaluated buprenorphine as a novel approach to addressing these challenges. With its unique pharmacological profile, buprenorphine shows promise compared with traditional opioids. Research presented by Mayuko Sakae, MD, at the 2024 Multinational Association of Supportive Care in Cancer (MASCC) Annual Meeting showed how this medication might help manage severe pain refractory to traditional opioids during BMT more effectively while minimizing opioid dose escalation and its associated AEs.

“Our study suggests that a timely collaboration with a supportive medicine specialty earlier in the process, before the pain level escalation, is beneficial,” explained Sakae, City of Hope assistant clinical professor, Department of Supportive Care Medicine, in an interview with Targeted Oncology^TM.

In the interview, Sakae further discussed this research on pain management for patients undergoing bone marrow transplants.

Targeted Oncology: Can you summarize the findings of your research presented at MASCC regarding refractory pain in patients who have undergone a bone marrow transplant?

Sakae: Our pilot prospective clinical trial was initiated after observing severe bone marrow transplant-related pain that our patients with sickle cell disease experienced. Their pain was uncontrolled even with the increasing use of multiple traditional opioid pain medications to high doses, which led to significant opioid side effects. Their pain was still uncontrollable by trying all the other pain management methods and techniques that we use when a specialty supportive medicine consult is requested for uncontrolled pain. This only changed when we introduced buprenorphine to the BMT pain management strategy for SCD patients in our pilot prospective clinical trial.

The number 1 key finding is that buprenorphine, an opioid pain medication with unique pharmacological properties, can provide effective pain management in patients suffering from uncontrolled pain with severe and complex pain history with significantly less opioid [adverse] effects. This means buprenorphine often causes less respiratory depression, less gastrointestinal adverse effects such as constipation, nausea, less euphoria and craving, and less depressant- and stress-causing neurotransmission compared with traditional full agonists.

Key point number 2 is that buprenorphine slows down the opioid tolerance development, meaning buprenorphine helps avoid further opioid dose-escalation, even in patients who have baseline hypersensitivity to pain. This would be an impossibility when we use traditional opioid pain medications like morphine, oxycodone, fentanyl, etc. Our study suggests that a timely collaboration with a supportive medicine specialty earlier in the process, before the pain level escalation, is beneficial.

Stem Cell Research and Regenerative Medicine: © mh.desing - stock.adobe.com

What were the most significant breakthroughs or new insights from this trial?

Our pilot prospective clinical trial outcomes suggest that buprenorphine does a superior job for the hospital level of acute severe pain management, even during the often painful bone marrow transplant process for patients with sickle cell disease. There is a growing body of literature about that impressive buprenorphine effect for patients with sickle cell disease with chronic pain that have failed sufficient pain relief by using a traditional opioid pain medication in an outpatient setting, but buprenorphine use for acute inpatient pain management has not been previously researched.

Could you elaborate on the patient population included in the study?

This clinical trial was for patients with sickle cell disease, mostly younger, with a severe form of disease, hemoglobin SS disease. These are the people who have experienced pain from infancy and very frequently all their life, meaning the brain's pain center and pain nerves were already set up for high resistance to large doses of opioid pain medication. Bone marrow transplant procedure usually leads to multisystemic pain syndrome, which can be difficult to control for anyone undergoing bone marrow transplant.

Did your research assess the impact of refractory pain and its management on patients' quality of life? What were some of the key findings in that area?

Quality of life is an important aspect of pain. How much the anticipatory anxiety, fear, and the resulting depression leads to the poor quality of life always needs to be addressed, not just the pain symptoms. Quality of life assessment was not part of the study, not done prospectively, but outside doctor’s post-BMT follow-up documentations have been reviewed retrospectively. We did find that patients who never received buprenorphine and left the hospital on huge doses of opioids mainly are still on the high dose opioids about a year after the bone marrow transplant, and that is 2 patients out of the 3 in our study including 1 with persistent depression. One of the 2 patients who received buprenorphine-based pain treatments during bone marrow transplant is not using any opioid pain medications anymore. The other one has reported a good quality of life.

What were some of the primary challenges encountered during the study?

Number 1 is the slow onset of action of the buprenorphine. Even if it is given by an IV shot, it takes about 30 to 45 minutes to kick in. That is difficult, especially for young patients experiencing acute pain who need something that works right away. That leads to a good benefit of buprenorphine. It is a partial mu-opioid receptor agonist, meaning it leaves some room for the opioid receptors to be bound to other opioid pain medications. While you are getting buprenorphine to prevent the severe pain in an around the clock schedule, it can also get a quick shot of IV fentanyl, which relieves the pain in 2-5 minutes. But using only buprenorphine during the time of highest pain intensity during BMT admission is a little challenging because of the slow peak effect.

Number 2, there is inconsistent availability of buprenorphine formulary in our hospital, because it is not a commonly used medication yet for cancer pain. We are a cancer center and pharmacy restrictions need some improvement. Every place, every order, every medication that doctors order in the hospital comes with some pharmacy restrictions that block the doctor from assigning them to be released. Because it is not as well studied as common medications like morphine, there are other restrictions that pharmacies place on the doctor’s order. It is just not a common mediation yet.

Lastly, insurance preauthorization or denial for the effective buprenorphine dosing when getting patients ready to discharge finally to go home with the home prescription. There are a few, and it just leads to the lack of a large number of randomized control trials that have proven that buprenorphine often is the number 1 for cancer pain treatment for severe cancer treatment-related pain that is not responding to massive loads of opioids and standard opioids.

Based on your research, what are the most promising avenues for the future, specifically in terms of cancer?

We conducted this pilot prospective clinical trial, inpatient pain management for patients with sickle cell disease with uncontrollable pain resistant to massive doses of full agonist opioids during their bone marrow transplant admission. We plan on developing a clinical trial of buprenorphine-based complex pain management for patients [with cancer] to compare with the sickle cell disease cohort who are undergoing bone marrow transplant. If successful, and similar results are proven, it will possibly enable us to create an official guideline to recommend early opioid rotation to buprenorphine by using high-risk criteria, or any patients who are likely to develop resistance to standard opioid pain medication before the pain management becomes difficult.

What is important for an oncologist to take away from this research?

It is important for the oncologist to put in the specialty pain management consult before the pain gets out of control. Oncologists are familiar with how to use morphine, how to use patient-controlled anesthesia, the pain pump, for the patient to use by pushing the button. But it does get complicated, especially for people like some patients with cancer with complex pain history, and they already are using a lot of pain medication. The brain’s pain center and the pain nerves have already developed hypersensitivity to pain. Then, it is more important to involve the pain medicine specialists early on. We can use all those methods and techniques that we use when a specialty pain consultant is requested for uncontrolled pain.