Abstract
The expanding therapeutic landscape of relapsed and/or refractory multiple myeloma (RRMM) has contributed to significant improvements in patient outcomes. These have included combinations of proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), monoclonal antibodies (mAbs), histone deacetylase inhibitors, and/or alkylating agents. More recently, the approval of the first-in-class nuclear export inhibitor selinexor and the first-in-class B-cell maturation antigen (BCMA) antibody-drug conjugate (ADC) belantamab mafodotin has helped address the current unmet need in patients refractory to PI, IMiD, and anti- CD38 mAb directed therapy, otherwise known as triple class refractory myeloma. With the growing number of treatment options in the RRMM therapeutic landscape, the choice and sequencing of drugs and combinations has become increasingly complex. In this review we discuss our approach and considerations in the treatment of both early and late RRRM based on best available data and our clinical experience.
Highlights
The patient in Case 1 represents proba- subset of lenalidomide refractory patients, bly the most common scenario encountered median progression free survival (PFS) was significantly higher in the Outcomes in multiple myeloma patients at first relapse in myeloma today given the daratumumab-Kd arm versus have improved substantially over the last prevalence of maintenance lenalidomide the Kd arm (11.1 months, hazard ratio (HR)10-15 years due to the incorporation of use in both transplant and non-transplant 0.47, 95% confidence interval (CI) 0.29-immunomodulatory drugs (IMiDs), protea- patients
Ethasone (DVd) was the first anti-CD38 monoclonal antibodies (mAbs) and proteasome inhibitors (PIs) combination to gain regulatory approval based on the CASTOR study which showed an improvement in progression free survival (PFS) compared to bortezomib and dexamethasone (Vd).[1]
The patient in Case 1 represents proba- subset of lenalidomide refractory patients, bly the most common scenario encountered median PFS was significantly higher in the Outcomes in multiple myeloma patients at first relapse in myeloma today given the daratumumab-Kd arm versus have improved substantially over the last prevalence of maintenance lenalidomide the Kd arm (11.1 months, hazard ratio (HR)
Summary
The patient in Case 1 represents proba- subset of lenalidomide refractory patients, bly the most common scenario encountered median PFS was significantly higher in the Outcomes in multiple myeloma patients at first relapse in myeloma today given the daratumumab-Kd arm (not-reached) versus have improved substantially over the last prevalence of maintenance lenalidomide the Kd arm (11.1 months, hazard ratio (HR)10-15 years due to the incorporation of use in both transplant and non-transplant 0.47, 95% confidence interval (CI) 0.29-immunomodulatory drugs (IMiDs), protea- patients. Ethasone (DVd) was the first anti-CD38 mAb and PI combination to gain regulatory approval based on the CASTOR study which showed an improvement in progression free survival (PFS) compared to bortezomib and dexamethasone (Vd).[1] among 18% of patients in the DVd arm who were refractory to lenalidomide in their last line of therapy, median PFS was only 9.3 months.[2] More recently, results from randomized phase 3 studies evaluating daratumumab (CANDOR) or isatuximab (IKEMA) in combination with the second generation PI carfilzomib and dexamethasone (Kd) versus Kd alone have been reported.
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