The Lancet: Nuclear export inhibitor XPOVIO significantly prolongs the progression-free survival of patients with relapsed or refrectable multiple myeloma

The Lancet published the results of a multi-center Phase 3 randomized clinical study, BOSTON (NCT03110562), on November 14th, involving 402 adult patients with relapsed or recurring multiple myeloma who had previously been treated one to three times.
The purpose of this study was to assess the efficacy and safety of the weekly oral nuclear export selective inhibitor XPOVIO (selinexor) in combination with the weekly Velcade (boratezomi) plus low-dose dexamethason (SVd) compared to standard therapies (Velcade plus small doses of dexamethason, Vd twice a week).
of the study was no progression lifetime (PFS), and the main secondary endpoints included overall remission rate (ORR) and peripheral neuropathy rate.
results showed that the median PFS in the SVd group was 13.93 months, compared with 9.46 months in the Vd group, indicating that the SVd treatment option increased the median PFS by 4.47 months (47%)compared to Vd.
, the SVd group also showed significantly higher ORR than the Vd group, at 62.3% and 76.4%, respectively, p s 0.0012.
patients who received only the previous treatment were also higher in the SVd group, at 65.7% and 80.8%, respectively, compared to the Vd group, with p s 0.0082.
, SVd showed consistent PFS extension and higher ORR in several important subgroups than Vd.
, the rate of peripheral neuropathy (PN) in SVd was also significantly lower than that of Vd, at 32.3% and 47.1%, respectively, and p was 0.0010.
the SVd ≥, the level 2 PN rate was also significantly lower than that of the Vd group, at 21.0% and 34.3%, respectively, and P was 0.0013.
most common emergency adverse events (AEs) for blood cell reduction and gastrointestinal symptoms, consistent with previous results reported in other selinexor studies.
adverse events can be controlled by adjusting dosages or standard support treatments.
the most common adverse events associated with hematology treatment were nausea (50%), fatigue (42%), decreased appetite (35%) and diarrhea (32%), mainly level 1 and 2 events.
the most common levels 3 and 4 AE associated with treatment were thyroid reduction (39 per cent), anaemia (16 per cent) and fatigue (13 per cent).
XPOVIO functions as an oral nuclear outlet (SINE) selective inhibitor for first-line therapy by selectively binding and inhibiting the nucleo-output protein 1 (XPO1, also known as CRM1).
XPOVIO causes these proteins to accumulate in the nucleation of cells to play an anti-cancer role by blocking the nucleation of tumor inhibitors, growth-regulating proteins, and anti-inflammatory proteins.
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