Extent of Prior Therapy Does Not Impact Radiotherapy Response in Myeloma

"In this large retrospective cohort of [patients with multiple myeloma], the number of systemic treatment lines administered before [radiotherapy] had no impact on the local response, confuting concerns of cross-resistance raised by multiple preclinical studies," according to the study authors.

The number of prior lines of therapy did not influence how patients with multiple myeloma locally responded to radiotherapy, according to findings from a retrospective study published in Advances in Radiation Oncology.1

Six-month local responses were evaluable for 217 lesions; 13.4% (n = 29) showed complete responses (CRs), 65% (n = 141) showed partial responses (PRs), 19.4% (n = 42) exhibited stable disease, and 2.3% (n = 5) demonstrated progressive disease. No significant influence on radiologic response was observed when considering the absolute number of prior therapy lines (P = .721) or categorizing patients based on whether they received 0, 1 to 2, or more than 2 lines before radiation (P = .623).

The biologically effective dose (RT BED10) demonstrated a significant impact on 6-month responses (P = .007), although radiotherapy technique did not significantly correlate with radiologic response at this time (P = .924). The use of MRI significantly correlated with a higher likelihood of PR and lower probability of stable disease vs CT scan, which investigators attributed to the former’s superior imaging quality for bone and soft tissue and capabilities for functional evaluation (P = .001).

At 1 month following radiation, the rates of complete control, partial control, and no control were 67.55%, 29.55%, and 2.90%, respectively. These respective rates were 75.13%, 21.99%, and 2.88% at 3 months following radiotherapy and 78.51%, 15.92%, and 5.57% at 6 months. The number of prior lines of therapy before radiotherapy did not show any significant association with pain control at 1 month (P = .134), 3 months (P = .763), and 6 months after completion of radiotherapy (P = .375).

“As the number of drugs approved for [multiple myeloma] has remarkably increased in recent years, with a consequent prognostic improvement, a large and growing proportion of patients who are candidates for [radiotherapy] have been heavily pretreated with several lines of therapy,” lead study author Andrea Emanuele Guerini, MD, from the Department of Radiation Oncology at University of Brescia and Spedali Civili Hospital in Italy, wrote with coauthors.1,2 “In this large retrospective cohort of [patients with multiple myeloma], the number of systemic treatment lines administered before [radiotherapy] had no impact on the local response, confuting concerns of cross-resistance raised by multiple preclinical studies. Disease control after [radiotherapy] was optimal, and instances of severe toxicities during treatment were rare.”

Investigators of this single-center retrospective study evaluated 665 multiple myeloma lesions in 366 patients who underwent radiotherapy from January 1, 2005, to January 31, 2023. Medical records provided information on radiotherapy, eventual systemic therapy, and patient and disease characteristics. Patients were sorted into subgroups based on number of systemic therapy lines before initiating radiotherapy as well as biologically effective radiotherapy doses of less than 15 Gy, 15 Gy to 38 Gy, and more than 38 Gy.

The study’s primary end point was 6-month radiologic local response per RECIST v1.1 or PERCIST v1.0 criteria. The secondary end point was toxicity observed during radiotherapy administration.

The median patient age was 70.1 years, and most of the population was male (50.5%). Additionally, most patients had no concurrent systemic therapy (35.5%) and treatment directed towards the vertebrae (60%). Most patients had 1 prior line of systemic treatment before beginning radiotherapy (37.2%) followed by no lines (19.2%), 2 lines (12.1%), 3 lines (11%), 6 or more lines (8.2%), and 4 or 5 lines (6.2% each). Three-dimensional conformal radiation therapy was the most common treatment modality used for this patient population (71.3%).

Regarding toxicities that were likely associated with radiotherapy during the treatment course, the most common grade 1 events included gastrointestinal (GI) toxicities (13%), esophagitis (10%), pain increase (7.1%), and pharyngodynia (4.5%). Grade 2 events consisted of GI toxicities (2%), esophagitis (0.6%), fatigue (0.3%), and mucositis (0.3%). Additionally, 1 patient experienced grade 3 esophagitis.

References

1. Guerini AE, Mataj E, Borghetti P, et al. Impact of the number of administered systemic treatment lines on local response to radiation therapy for multiple myeloma. Adv Radiat Oncol. 2024;10(3):101696. doi:10.1016/j.adro.2024.101696.
2. Puertas B, Gonzalez-Calle V, Sobejano-Fuertes E, et al. Novel agents as main drivers for continued improvement in survival in multiple myeloma. Cancers (Basel). 2023;15(5):1558. doi:10.3390/cancers15051558