Why this matters
Radiotherapy is highly effective for painful bone involvement in multiple myeloma, but these patients may receive treatment to multiple sites over the course of their disease and often have substantial prior systemic therapy.
Because irradiated bone contains active marrow, reducing unnecessary radiation exposure could be particularly valuable in myeloma. The question is whether a much lower dose than commonly used palliative regimens can provide adequate pain relief while preserving the option of additional treatment when needed.
This prospective phase II study tested a simple response-adapted strategy: begin with only 4 Gy and reserve additional radiotherapy for patients with inadequate pain control.
Study design
This prospective multi-institutional single-arm phase II study enrolled patients with uncomplicated painful bone lesions from multiple myeloma.
Patients received a total dose of 4 Gy using either:
- 4 Gy in 1 fraction
- 2 Gy in 2 fractions
Pain response was evaluated using the Brief Pain Inventory together with changes in oral morphine equivalent dose according to international consensus criteria for palliative radiotherapy.
The primary endpoint was self-reported pain response at 4 weeks.
Patients with inadequate pain control could receive a second course of radiotherapy from 4 weeks onward using a clinician-selected regimen.
A total of 63 evaluable patients with 70 lesions were treated across 7 institutions between 2019 and 2025. Twenty-nine percent received a single 4 Gy fraction.
Median follow-up after radiotherapy was 186 days.
Key results
Among patients who completed the relevant questionnaires, pain response increased over time:
- 4 weeks: 59%
- 8 weeks: 63%
- 6 months: 82%
Median time to pain relief was 36 days, and the median duration of pain response was 148 days.
There was no observed difference in pain relief between the single-fraction and two-fraction 4 Gy schedules.
Only 24% of patients required a second course of radiotherapy.
Reirradiation was delivered at a median of 71 days after the initial 4 Gy course, with a median retreatment dose of 20 Gy. Among retreatreated patients, the pain response rate at 4 weeks after the second course was 63%.
No grade 3 or higher treatment-related toxicity was reported.
Interpretation
The most clinically interesting aspect of this study is not simply that 4 Gy produced pain relief.
It is that an ultralow-dose first treatment allowed the majority of patients to avoid further radiotherapy during the observed follow-up period.
Only 24% required a second course, meaning that approximately three-quarters of patients were managed without escalation beyond the initial 4 Gy treatment.
That supports a different way of thinking about palliation in multiple myeloma. Instead of selecting a higher dose upfront for every painful lesion, clinicians could potentially begin with a very low dose and escalate only for patients who do not achieve adequate symptom control.
This approach may be particularly attractive in myeloma because patients can accumulate multiple courses of therapy over many years and preservation of bone marrow is clinically relevant.
However, the increasing response rate over time needs careful interpretation. The reported 59%, 63%, and 82% response rates refer to patients completing questionnaires at those time points and should not automatically be interpreted as response rates for the entire original cohort.
The median time to pain relief of 36 days is also important. A 4 Gy strategy may be less attractive when very rapid symptom relief is required, although the study does not provide a randomized comparison of response kinetics against standard palliative regimens.
Limitations
This was a single-arm phase II study without a conventional-dose control group.
It therefore cannot establish that 4 Gy provides equivalent pain control to commonly used palliative schedules.
The study included only 63 evaluable patients, and later pain-response estimates are influenced by questionnaire completion and follow-up.
The two 4 Gy fractionation strategies were not randomized against each other.
The study also focused on uncomplicated painful bone lesions, so these findings should not automatically be extrapolated to lesions requiring more intensive local treatment because of instability, neurologic compromise, or other high-risk features.