Treatment of multiple myeloma-related bone disease: recommendations from the Bone Working Group of the International Myeloma Working Group

In this Policy Review, the Bone Working Group of the International Myeloma Working Group updates its clinical practice recommendations for the management of multiple myeloma-related bone disease. After assessing the available literature and grading recommendations using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) method, experts from the working group recommend zoledronic acid as the preferred bone-targeted agent for patients with newly diagnosed multiple myeloma, with or without multiple myeloma-related bone disease. Once patients achieve a very good partial response or better, after receiving monthly zoledronic acid for at least 12 months, the treating physician can consider decreasing the frequency of or discontinuing zoledronic acid treatment. Denosumab can also be considered for the treatment of multiple myeloma-related bone disease, particularly in patients with renal impairment. Denosumab might prolong progression-free survival in patients with newly diagnosed multiple myeloma who have multiple myeloma-related bone disease and who are eligible for autologous stem-cell transplantation. Denosumab discontinuation is challenging due to the rebound effect. The Bone Working Group of the International Myeloma Working Group also found cement augmentation to be effective for painful vertebral compression fractures. Radiotherapy is recommended for uncontrolled pain, impeding or symptomatic spinal cord compression, or pathological fractures. Surgery should be used for the prevention and restoration of long-bone pathological fractures, vertebral column instability, and spinal cord compression with bone fragments within the spinal route.

Important points:

1. Treatment options for relapsed and refractory multiple myeloma depend on previous treatment history and patient-related factors. ​
2. Daratumumab-based regimens, such as daratumumab plus lenalidomide plus dexamethasone, and carfilzomib-based regimens, such as carfilzomib plus lenalidomide plus dexamethasone, have shown improved outcomes in terms of progression-free survival and overall survival. ​
3. Bortezomib-based regimens, with or without additional agents, are commonly used in relapsed and refractory multiple myeloma. ​
4. Pomalidomide plus dexamethasone is considered standard of care for patients whose disease has progressed after treatment with bortezomib and lenalidomide. ​
5. Isatuximab plus pomalidomide plus dexamethasone, daratumumab plus pomalidomide plus dexamethasone, and elotuzumab plus pomalidomide plus dexamethasone have shown benefits in patients previously treated with multiple lines of therapy. ​
6. Salvage autologous stem-cell transplantation can be considered in patients who have not previously received a transplant, and it may also be an option for patients progressing after front-line autologous stem-cell transplantation. ​
7. CAR T-cell therapy and BCMA-targeting agents, such as belantamab mafodotin, show promise in relapsed and refractory multiple myeloma. ​
8. Cost considerations and drug access are significant issues in the treatment of multiple myeloma. ​
9. Enrolling patients in clinical trials should be considered when available. ​

 

Authors:

Prof Evangelos Terpos, MD, Elena Zamagni, MD, Prof Suzanne Lentzsch, MD, Matthew T Drake, MD, Ramón García-Sanz, MD, Prof Niels Abildgaard, MD, Ioannis Ntanasis-Stathopoulos, MD, Fredrik Schjesvold, MD, Javier de la Rubia, MD, Charalampia Kyriakou, MD, Prof Jens Hillengass, MD, Prof Sonja Zweegman, MD, Prof Michele Cavo, MD, Prof Philippe Moreau, MD, Prof Jesus San-Miguel, MD, Prof Meletios A Dimopoulos, MD, Prof Nikhil Munshi, MD, Prof Brian G M Durie, MD, Prof Noopur Raje, MD

Citation:

POLICY REVIEW| VOLUME 22, ISSUE 3, E119-E130, MARCH 01, 202
https://doi.org/10.1016/S1470-2045(20)30559-3