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Immunologic Profile of Patients With High-Risk Smoldering Myeloma

By: Joshua D. Madera, MS
Posted: Friday, February 3, 2023

For some patients with high-risk smoldering myeloma, the use of a combination therapy of immunotherapy and standard treatment—elotuzumab, lenalidomide, and dexamethasone (triplet regimen)—may be an effective alternative option, according to the results of a phase II clinical trial published in Cancer Cell. The efficacious impact of this combination therapy was more pronounced in patients with increased levels of granzyme K–positive, CD8-positive effector memory T cells, explained Irene M. Ghobrial, MD, of Dana-Farber Cancer Institute, Boston, and colleagues.

“Our results show that by taking an ‘immunological profile’ of patients with high-risk smoldering myeloma, we may be able to identify those who stand to be helped by therapy,” stated coauthor Romanos Sklavenitis-Pistofidis, MD, also of Dana-Farber, in an institutional press release.

From 2015 to 2016, a total of 51 patients with high-risk smoldering multiple myeloma were recruited for the study. Patients were stratified into two groups and received treatment with elotuzumab and lenalidomide alone (n = 11) or with the triplet regimen (n = 40).

As part of the study, the researchers collected 149 blood and bone marrow samples from the patients and from people without smoldering myeloma and separated out the immune system cells from each sample. They then analyzed the RNA within these cells, which enabled them to detect changes in gene expression and in the T-cell receptor.

The study findings showed a response rate of 87% in patients who received the triplet combination therapy. Additionally, 95.6% of these patients were still alive 2 years after treatment. Furthermore, rates of median progression-free survival and overall survival at the 48-month interval were 88.7% and 95.6%, respectively. In addition, the investigators found that patients whose immune cell composition in the bone marrow was least like that of healthy individuals had a significantly longer progression-free survival.

Adverse effects related to treatment included hypophosphatemia (37%), neutropenia (26%), and lymphocytopenia (22%). Despite prophylactic therapy, thromboembolic events were observed in 12% of patients.

Disclosure: For full disclosures of the study authors, visit

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