Treatment of Relapsed Multiple Myeloma

Initial Assessment and Risk Stratification

The International Myeloma Society recommends that all patients undergo full staging and risk stratification at relapse to determine whether they have aggressive vs indolent relapse and standard-, intermediate-, or high-risk relapsed multiple myeloma 2, 3
Evaluation should include FISH data on relapsed bone marrow to detect high-risk cytogenetic abnormalities, assessment of prior treatment response duration and quality, evaluation for extramedullary disease and new bone lesions, and review of previous adverse effects to guide therapy selection 1, 2

The Mayo Clinic recommends considering salvage autologous stem cell transplantation (ASCT) in fit patients with indolent relapse who had a meaningful response to first transplant, with a median time to progression of 19 months with second ASCT vs 11 months with cyclophosphamide 2, 4
The American Society of Clinical Oncology suggests that triple combination therapy is preferred when patients can tolerate it, with options including daratumumab-based regimens, carfilzomib-based regimens, ixazomib-based regimens, and elotuzumab-based regimens 1, 2, 5, 6

For patients refractory to prior therapies, the National Comprehensive Cancer Network recommends using PI-based regimens for IMiD refractory patients and IMiD-based regimens for PI refractory patients 5, 6
For dual refractory patients, pomalidomide-based regimens and daratumumab-based regimens are recommended 5, 6

The European Society for Medical Oncology suggests treating until plateau is reached for indolent relapse, and continuing therapy until progression or significant toxicity for aggressive relapse 2
For high-risk disease, continuous treatment is recommended to keep disease burden low and reduce risk of additional mutations 3

For high-risk cytogenetics, the International Myeloma Society recommends continuous therapy as progression-free survival is generally shorter 3
For early relapse, consider as high-risk disease regardless of cytogenetic profile 3
For extramedullary disease, a more aggressive approach with combination therapies is needed 5