Current Treatment Options for Multiple Myeloma
Multiple myeloma (MM) accounts for about 10% of all hematologic malignancies. Thanks to advancements in diagnostic methods, it is now understood as a collection of several cytologically distinct plasma cell malignancies. Alongside progress in diagnostics, there has also been rapid development in therapy, significantly improving survival rates for this previously very unfavorable diagnosis, especially in the last 15 years.
Introduction
Each year, the development of new drugs leads to new therapeutic regimens for various hemato-oncological diagnoses, including multiple myeloma. Currently, several therapeutic modalities are available for MM patients, in addition to classical pharmacotherapy such as alkylating cytostatics and corticosteroids. These include traditional immunomodulatory drugs (thalidomide, lenalidomide, pomalidomide), proteasome inhibitors (bortezomib, carfilzomib, ixazomib), monoclonal antibodies (elotuzumab, daratumumab), and deacetylase inhibitors (panobinostat).
Recent data show that a negative minimal residual disease (MRD) status has favorable prognostic value. However, more studies are needed to clarify whether therapeutic changes are necessary according to MRD status. Currently, MRD assessment is recommended as a prognostic tool, not as a method for deciding further therapy.
Current Approaches to Multiple Myeloma Therapy
Initial treatment for transplant-eligible patients typically involves 3–4 cycles of induction therapy with bortezomib, lenalidomide, and dexamethasone (VRd) before stem cell collection. If lenalidomide is unavailable or if there is acute renal failure, other bortezomib-based regimens, such as bortezomib, thalidomide, dexamethasone (VTd) or bortezomib, cyclophosphamide, dexamethasone (VCd), may be used.
After stem cell collection, patients may undergo transplantation or continue induction therapy until the first relapse. Therapeutic regimens prefer low-dose dexamethasone (40 mg once weekly) to minimize treatment toxicity. Similarly, bortezomib neurotoxicity can be reduced by weekly subcutaneous administration.
New initial therapy options for younger patients include carfilzomib, lenalidomide, dexamethasone (KRd), daratumumab, lenalidomide, dexamethasone (DRd), and daratumumab combined with VRd. Further data are needed to evaluate the efficacy of these regimens compared to VRd.
For patients ineligible for stem cell transplantation due to age or comorbidities, initial treatment involves 8–12 cycles of VRd, followed by lenalidomide maintenance. Alternatives for these patients include VCd and VTd.
A recent study compared early versus delayed stem cell transplantation after initial VRd therapy followed by lenalidomide maintenance. Early transplantation showed significant improvement in progression-free survival but did not affect overall survival. Allogeneic transplantation research continues, and it may be considered for high-risk disease patients in the first relapse.
Lenalidomide maintenance is standard in therapy. Clinical trial meta-analyses showed significant increases in progression-free and overall survival in patients receiving lenalidomide compared to placebo or no therapy. High-risk patients should consider bortezomib-based regimens.
Almost all multiple myeloma patients eventually relapse. Choosing a treatment regimen for relapse is difficult and depends on several factors. Suitable patients should consider transplantation if they haven’t undergone it previously or had an excellent remission period after the first transplant. VRd, VCd, and VTd are the main active regimens upon initial disease detection. Daratumumab-based regimens have proven effective in relapsed MM. Various other regimens, including promising experimental drugs, are being researched for relapsing MM.
Conclusion
Clinical research in multiple myeloma has achieved significant successes, reflected in new treatment options. Currently, multiple therapeutic regimens are available for MM patients, with indications depending on disease stage, age, and comorbidities.
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Source: Rajkumar S. V. Multiple myeloma: Every year a new standard? Hematol Oncol 2019; 37 (Suppl. 1): 62–65, doi: 10.1002/hon.2586.
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