Ultralow-Dose RT Quells Bone Pain in Myeloma, Preserves Bone Marrow

Ultralow-dose radiation therapy (RT) provided durable pain relief from multiple myeloma bone metastases with few adverse effects and minimal impact on bone marrow status, a prospective clinical trial showed.

Two-thirds of evaluable patients had a complete or partial pain response at 4 weeks, increasing to 86% at 6 months with either a single 4-Gy RT or two 2-Gy doses, both well below the usual 30-Gy dose in 10 fractions administered for bone pain. Treatment-related adverse events occurred in five of 69 patients, none of which reached grade ≥3 severity or required treatment interruption or modification.

Bone marrow status was not adversely affected, allowing re-irradiation if needed, which was an infrequent event, reported Leslie Ballas, MD, of Cedars-Sinai Medical Center in Los Angeles, at the American Society for Radiation Oncology (ASTRO) meeting in Boston.

“The bone marrow is protected, which allows patients to get re-irradiation, maintain their blood counts, continue chemotherapy, and have room for future therapies such as transplant or CAR T-cell therapy,” said Ballas. “This truly is a risk-adapted approach to radiation. Only 19% of patients needed a second course, but it is still available to them at any point during their lifetime.”

In response to a question, Ballas said additional clinical trials probably are unnecessary.

“The data for this single-arm phase II trial compared favorably to historical controls when done in a prospective fashion,” she said. “I think that 2 Gy times two or 4 Gy times one is, at this point, ready for clinical practice, as long as patients are appropriately counseled that it is a risk-adapted approach and that a small number of patients may need re-irradiation. We feel very good about this.”

The “exciting prospective, single-arm phase II study” addressed a common complication of multiple myeloma that frequently leads to referrals for radiotherapy, said ASTRO expert Chelsea Pinnix, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“The findings suggest that many patients can experience meaningful pain relief with a very low initial radiation dose,” said Pinnix. “This approach is convenient for patients, but most importantly, it provides excellent pain relief with minimal side effects. The results may help clinicians consider radiotherapy earlier in the course of care for patients with multiple myeloma experiencing painful bone disease.”

Providing context for the study, Ballas noted that prior studies of palliative RT in multiple myeloma were mostly retrospective and observational. The only prospective data came from a randomized comparison of 30 Gy versus 8 Gy and measured pain by means of a visual analog scale and use of analgesic medications. The results showed that about 80% of patients achieved a complete or partial response.

The most recent study was a retrospective evaluation of 35 patients with bone pain, including 11 with multiple myeloma treated with low-dose RT. Subsequently, 95% of the patients with myeloma met criteria for pain response, as did 98% of the remaining patients whose bone pain was treated with a high-dose protocol.

The need for low-dose palliative RT options in myeloma has evolved from the changing clinical landscape of the disease.

“There have been significant advances in therapeutic agents, and the 5-year overall survival has increased to 64%,” said Ballas. “Patients are receiving multiple lines of therapy over their lifetime and need their bone marrow. Because radiation can be used from diagnosis to death and often more than once in this population, the effect on bone marrow is an important consideration. The bone marrow volume receiving 10 Gy or higher has been shown to correlate strongly with hematologic adverse events.”

An RT dose of 4 Gy in two fractions has a precedent in indolent lymphoma, which has a radiosensitivity similar to myeloma, she continued. Data have shown pain response rates of 80-90% with 2 Gy times two. A single 4-Gy dose might provide similar pain relief with greater patient convenience.

Investigators enrolled 69 patients with multiple myeloma and painful bone lesions, defined by a Brief Pain Inventory (BPI) score ≥2. Eligible patients had no prior RT or surgery, pathologic fracture in a long bone, spinal cord compression, or skull base or orbital index lesions. The patients were randomized to a 4-Gy RT dose administered in a single fraction or in two 2-Gy fractions.

The primary outcome was pain response plus daily oral morphine equivalent dose (OMED) at 4 weeks. A complete response was defined as a BPI score of 0 at the treated site and no increase in OMED. A partial response was pain decrease ≥2 points or an OMED decrease ≥25%. Response data were derived from patients who completed questionnaires at 4 weeks, 8 weeks, and 6 months.

The 66% pain response rate at 4 weeks was based on 61 completed questionnaires. The rate dipped to 64% (47 questionnaires) at 8 weeks, before surging to 86% at 6 months (42 questionnaires). Response rates for patients treated with one or two fractions were similar at all time points, although Ballas noted that the median BPI decrease favored the two-fraction protocol at 6 months (2.2 vs 4.1, P=0.01).

Twelve of 63 (19%) patients required re-irradiation at doses ranging from 8-24 Gy (median 20 Gy). Median time to re-irradiation was 61 days, and the pain response rate after re-irradiation was 69%.