A short course of ultra–low-dose radiation therapy relieved painful bone lesions from multiple myeloma for patients in a multi-institutional phase II clinical trial. The findings suggest that a lower-intensity approach could help ease patients’ pain without interrupting other treatment and with few adverse effects. Data were presented at the 2026 American Society for Radiation Oncology (ASTRO) Annual Meeting (Abstract 10).
The study found that a very low dose of radiation therapy, delivered in one or two treatments, produced pain responses that persisted over time and provided relief for patients, with 81% achieving pain control without additional radiation. Low-grade fatigue was a radiation treatment side effect.
“Multiple myeloma is extremely sensitive to radiation therapy, and our study shows that a very low dose can provide meaningful pain relief for most patients with uncomplicated bone lesions,” said Leslie Ballas, MD, FASTRO, principal investigator of the trial and a Professor of Radiation Oncology at Cedars Sinai. “Because this approach is brief and uses a lower dose, it may make clinicians more comfortable referring patients earlier, so their patients don’t have to live with pain while waiting for other treatments to work.”
Bone disease is a defining complication of multiple myeloma, leading to pain, fractures, and reduced quality of life for many patients. Radiation therapy is commonly used to relieve painful lesions, but patients often are referred later in their care after symptoms worsen, in part due to concerns about effects on healthy bone marrow or the logistics of coordinating radiation treatment with systemic therapy.
Because multiple myeloma is highly sensitive to radiation, lower doses may effectively treat painful bone lesions while limiting exposure to healthy bone marrow. This trial tested whether an especially low dose could provide adequate pain relief, an approach informed by longstanding experience using ultra–low-dose radiation therapy for similarly radiosensitive lymphomas.
“The aim is to start with a dose that is enough to relieve pain but low enough to preserve bone marrow and leave room to add more radiation if needed,” Dr. Ballas said. “That flexibility may help patients access radiation therapy earlier in their disease course and still keep future treatment options open.”
Trial Methodology and Pain Control Results
The prospective, single-arm phase II trial enrolled patients at seven institutions. Eligible patients had bone lesions that were painful but not causing spinal cord compression, pathologic fracture of a long bone, or other urgent complications. Participants received 4 Gy of radiation, either as one treatment of 4 Gy or two treatments of 2 Gy each.
Researchers assessed pain response from 63 evaluable patients at 4 weeks, 8 weeks, and 6 months using patient-reported Brief Pain Inventory scores and oral morphine equivalent dosing, based on international consensus criteria for palliative radiation therapy. The primary endpoint was patient-reported pain response at 4 weeks. Patients who did not experience adequate pain control could receive additional radiation therapy starting at 4 weeks after their first treatment.
Three in five patients reported pain relief within the first month of treatment, increasing to four in five patients reporting pain relief by 6 months. Among patients who completed questionnaires, pain reduction was 66% at 4 weeks after treatment, 64% at 8 weeks, and 86% at 6 months. The median time to pain relief was 36 days, and the median duration of pain relief was 148 days. Outcomes were similar for patients treated in one session or two.
Overall, 19% of patients received a second course of radiation therapy to the same site, at a median of 71 days after the initial treatment. After re-irradiation, the pain response rate was 63% at 4 weeks. Four patients experienced grade 1 or 2 fatigue, and one patient reported mild radiation-related skin changes.
For many patients, the initial low-dose treatment was sufficient to control symptoms without further radiation therapy, Dr. Ballas said. “Four out of five patients did not need more radiation therapy after the first course, which tells us this strategy can provide effective pain control without interrupting other treatments and with almost no side effects to the patient.”
Next Steps
The findings are especially important for people with multiple myeloma, who often develop multiple painful lesions over time and may require palliative radiation therapy on several occasions. The shorter course may also make radiation therapy easier to integrate with systemic therapy and allow for healthy bone marrow function.
“My hope is that these findings will help more [patients with] multiple myeloma receive pain relief more quickly,” said Dr. Ballas. "Even though this is a relatively small study, we now have prospective data from multiple institutions showing that this approach can provide meaningful pain relief with minimal side effects, making it a practical and flexible strategy for routine clinical care."
Dr. Ballas said that the next steps for this research include determining whether some patients with multiple myeloma might benefit from low-dose radiation therapy earlier in the course of bone disease, before pain becomes severe, and identifying which lesions are most likely to respond to this approach.
“As patients live longer and receive more lines of therapy, preserving bone marrow function and reducing time in treatment become more important,” Dr. Ballas said. “This study suggests we may be able to address pain, with less treatment, for many patients.”
DISCLOSURE: For full disclosures of the study authors, visit elsevierdigitaledition.com (Abstract 10).
