Bortezomib based regimes have become the standard of care for front line treatment of systemic AL amyloidosis. Rapidity of response is one of the key factors in determining survival–patients achieving deeper responses have significantly better outcomes. Most patients are treated with cyclophosphamide (or melphalan)-bortezomib-dexamethasone based on previous reports from our and other centres. Dexamethasone, a key component of the regime, has significant toxicity and the long half-life predisposes to fluid retention.
We report the use of high dose methylprednisolone as an alternative to high dose dexamethasone with better responses, survival and tolerance.
We report matched outcomes (matched for Mayo cardiac stage, presenting serum free light chains and use of doxycycline) of two cohorts of 26 patients each with systemic AL patients treated with weekly Velcade plus Methylprednisolone and Velcade plus Dexamethasone (+Cyclophosphamide or Thalidomide in each case) respectively. Both cohorts received oral doxycycline 100 mg BD. The doses of dexamethasone were 20-40 mg weekly orally compared to those of methylprednisolone 500-750 mg intravenously weekly. The FLC measurements were monitored monthly to assessment ongoing treatment response.
The median age in both groups were 69.2 and 67.3 years, all having cardiac involvement (Mayo stage 2 in 3 patients; 11.6%, Mayo stage 3A in 15 patients; 57.7%, Mayo stage 3B in 8 patients; 30.7%) in both groups and renal involvement in 50.0% and 69.2% in the Methylprednisolone and Dexamethasone cohorts respectively. Haematological responses at 1 month/2 months were as follows: CR: 11.5% and 7.7%/26.9% and 19.2, VGPR 0 and 7.7%/7.7% and 0, PR 38.5% and 30.8%/42.3% and 50%, in the Methylprednisolone and Dexamethasone groups: respectively. The median survival was not reached in the Methylprednisolone cohort and was 21.6 months in the Dexamethasone cohort. The 2 year OS in the Methylprednisolone and Dexamethasone groups were 65.4% and 43.1% with 12 and 14 deaths respectively. Methylprednislolone appeared to be better tolerated with less fluid overload and hospital admissions.
Bortezomib based regimes with either Methylprednisolone and Dexamethasone achieve excellent good haematological responses. However, the Methylprednisolone cohort showed faster haematological responses which translated into an improved OS in comparison to the Dexamethasone cohort. This preliminary data suggests that a review of dexamethasone in AL amyloidosis with alternatives should be considered in further prospective studies.