From the FDA Drug Label
The approval of XPOVIO was based upon the efficacy and safety in a prespecified subgroup analysis of the 83 patients whose disease was refractory to bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab, as the benefit-risk ratio appeared to be greater in this more heavily pretreated population than in the overall trial population Table 15: Disease Characteristics (STORM) Parameter STORM (n=83) Median years from diagnosis to start of study treatment (range) 7 (1,23) Prior treatment regimens, median (range) 8 (4,18) Documented refractory status, n (%) Lenalidomide 83 (100) Pomalidomide 83 (100) Bortezomib 83 (100) Carfilzomib 83 (100) Daratumumab 83 (100) Documented refractory status to specific combinations, n (%) Bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab 83 (100) Daratumumab in any combination 57 (69) Daratumumab as single agent (+/- dexamethasone) 26 (31) Previous stem cell transplant, n (%) 67 (81) Revised International Staging System at Baseline, n (%) I 10 (12) II 56 (68) III 17 (21) Unknown 0 High-risk cytogeneticsa, n (%) 47 (57)
Double Hit and Triple Hit Multiple Myeloma Treatment:
- The provided drug label does not directly address the treatment of double hit and triple hit multiple myeloma.
- However, it does discuss the treatment of relapsed or refractory multiple myeloma with XPOVIO in combination with dexamethasone, which may be relevant to patients with double hit or triple hit disease who have received prior therapies.
- Key Points:
- XPOVIO is approved for use in combination with dexamethasone for the treatment of adults with multiple myeloma who have received at least 4 prior therapies and are refractory to at least 2 proteasome inhibitor medicines, at least 2 immunomodulatory agents, and an anti-CD38 monoclonal antibody medicine.
- The efficacy of XPOVIO was evaluated in a subgroup analysis of patients with relapsed or refractory multiple myeloma who were refractory to bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab.
- The overall response rate in this subgroup was 25.3% 1. However, the label does not provide specific information on the treatment of double hit and triple hit multiple myeloma.
From the Research
Double-hit and triple-hit multiple myeloma treatments should involve intensive combination therapies, including proteasome inhibitors, immunomodulatory drugs, and dexamethasone, with consideration of anti-CD38 monoclonal antibodies, due to their aggressive nature and poor prognosis. The most recent and highest quality study, 2, published in 2024, provides guidance on the diagnosis, risk-stratification, and management of multiple myeloma. According to this study, the presence of del(17p), t(4;14), t(14;16), t(14;20), gain 1q, del 1p, or p53 mutation is considered high-risk multiple myeloma, and the presence of any two high-risk factors is considered double-hit myeloma, while three or more high-risk factors is considered triple-hit myeloma.
Some key points to consider in the treatment of double-hit and triple-hit multiple myeloma include:
- The use of anti-CD38 monoclonal antibodies, such as daratumumab, in combination with bortezomib, lenalidomide, and dexamethasone (VRd) as induction therapy, followed by autologous stem cell transplantation (ASCT) for eligible patients, as supported by the GRIFFIN trial 3
- The consideration of quadruplet regimens, such as DaraKRd (daratumumab, carfilzomib, lenalidomide, dexamethasone), for triple-hit myeloma, due to its aggressive nature and poor prognosis
- The importance of tailoring treatment to the patient's specific genetic profile, age, comorbidities, and previous therapies, with close monitoring for response and early adjustment if the disease shows inadequate response
- The use of maintenance therapy, often with a proteasome inhibitor plus lenalidomide, to prolong progression-free survival and overall survival
Overall, the treatment of double-hit and triple-hit multiple myeloma requires a comprehensive and individualized approach, taking into account the latest evidence and guidelines, to optimize outcomes and improve quality of life for patients with these aggressive and complex diseases.