Multiple myeloma is a type of cancer that originates in the plasma cells, a type of white blood cell found in the bone marrow. These cancerous plasma cells can accumulate in the bone marrow, interfering with the production of normal blood cells and causing various symptoms. An autologous stem cell transplant (ASCT) is a commonly used and effective treatment approach for eligible individuals with multiple myeloma. This procedure aims to replace bone marrow damaged by myeloma cells with healthy, blood-forming stem cells.
Understanding Remission After Transplant
After an autologous stem cell transplant, “remission” indicates a decrease in or disappearance of multiple myeloma symptoms. While a transplant can lead to remission, it is not considered a cure, as some cancer cells remain in the body. Remission duration varies, with many patients experiencing a first remission lasting two years or more.
Remission can be classified into different categories based on the extent of cancer cell reduction. A “partial response” means doctors still detect some cancer markers, though tumors have shrunk and cancer cell numbers are reduced. A “very good partial response” signifies a higher level of reduction, with marker levels dropping by at least 90%. “Complete response” indicates no M-proteins in blood or urine and no detectable tumors, though up to 5% myeloma cells might still be present in the bone marrow.
More sensitive tests detect “minimal residual disease” (MRD), the presence of very small numbers of myeloma cells undetectable by conventional methods. MRD negativity, defined as fewer than 1 clonal plasma cell in 100,000 cells in the bone marrow, predicts longer progression-free and overall survival. Patients achieving MRD negativity have better long-term outcomes, with some studies showing a median progression-free survival of 56 months for MRD-negative patients compared to 34 months for MRD-positive patients.
Factors Influencing Remission Duration
Several elements influence how long a patient remains in remission following an ASCT. The initial stage and aggressiveness of the myeloma play a role. Patients with a lower disease burden or less aggressive myeloma at diagnosis may experience longer remission periods.
Specific genetic abnormalities within myeloma cells are also prognostic indicators. High-risk cytogenetics, such as deletions on chromosome 17p (del(17p)) or translocations involving chromosomes 4 and 14 (t(4;14)) or 14 and 16 (t(14;16)), are associated with shorter progression-free survival. Patients without these high-risk genetic features tend to have more durable remissions.
The patient’s overall health and age at transplant also affect remission duration. Younger patients and those in better health tolerate high-dose chemotherapy and transplant more effectively, contributing to deeper, more sustained responses. The depth of response achieved immediately after transplant, particularly MRD negativity, predicts longer progression-free survival.
Strategies for Sustaining Remission
Maintenance therapy is a common strategy after an ASCT to prolong remission and delay myeloma’s return. This involves ongoing medication administered after transplant to keep remaining myeloma cells at bay. It aims to extend disease control as long as possible.
Lenalidomide is a frequently used medication for maintenance therapy, currently the only single agent approved by the U.S. Food and Drug Administration (FDA) for this purpose after an ASCT. Studies show lenalidomide maintenance improves progression-free survival, extending remission from approximately 30 months to 57 months compared to no maintenance. Bortezomib and ixazomib, proteasome inhibitors, are also used, particularly in patients with high-risk genetic abnormalities.
Regular follow-up appointments and ongoing monitoring are components of sustaining remission. These appointments allow healthcare providers to track the patient’s response to maintenance therapy, monitor for disease recurrence, and manage side effects. Maintenance therapy choice and duration are personalized based on factors like prior treatments, disease risk, and patient tolerance.
Managing Myeloma After Relapse
Despite achieving remission, multiple myeloma often returns. However, relapse does not signify the end of treatment options, as numerous therapies are available. The approach to treating relapsed myeloma is highly individualized, considering previous treatments, prior remission duration, and current disease characteristics.
Treatment for relapsed myeloma often involves different drug combinations, including re-treatment with previously effective therapies if remission lasted a year or longer. Novel drug classes have expanded the treatment landscape for relapsed disease. These include immunomodulatory drugs like pomalidomide, proteasome inhibitors such as carfilzomib, and monoclonal antibodies like daratumumab and isatuximab.
Advanced therapies, such as CAR T-cell therapy and bispecific antibodies, are emerging as options for patients with relapsed or refractory myeloma, offering new hope even for those with limited prior choices. Clinical trials play a role in exploring new treatments and combinations, providing access to new therapies. The ongoing development of diverse treatment modalities aims to provide patients with effective options for further disease control.