AT ASH 2016

SAN DIEGO (FRONTLINE MEDICAL NEWS) – Adding bortezomib (B) to melphalan and dexamethasone (MDex) increased the frequency and depth of hematologic responses in a phase III trial of patients with previously untreated immunoglobulin light-chain (AL) amyloidosis.

Rates of hematologic response after three treatment cycles were 79% for BMDex and 52% for MDex (P = .002), Efstathios Kastritis, MD, said at the annual meeting of the American Society of Hematology. Very good partial responses accounted for most of this difference, with rates of 45% and 25%, respectively (P = .02). This first-in-kind trial establishes BMDex “as a novel standard of care in AL amyloidosis,” Dr. Kastritis concluded.

MDex is a standard regimen in intermediate-risk AL amyloidosis, while single-agent therapy with bortezomib yielded a median overall survival time of more than 5 years in one study , noted Dr. Kastritis of the University of Athens. In another matched case-control study , BMDex outperformed MDex based on overall response (69% vs. 51%; P = .01) and complete response (42% vs. 19%; P = .002).

Therefore, Dr. Kastritis and his associates in Europe and Australia randomly assigned 110 patients with newly diagnosed AL amyloidosis to receive either MDex (0.22 mg/kg melphalan plus 40 mg dexamethasone daily for 4 consecutive days every 28 days) or BMDex (MDex plus 1.3 mg/m2 bortezomib on days 1, 4, 8, and 11 during cycles one and two, and on days 1, 8, 15, and 22 during subsequent cycles). Treatment continued through nine cycles of MDex or eight cycles of BMDex, or through cycle six if patients had either a complete response or a partial response plus an organ response. Patients stopped treatment after three cycles if they did not have at least a partial response.

After a median of five treatment cycles, BMDex and MDex led to similar rates of complete response (23% vs. 20%), partial response (19% and 17%), cardiac response (38% vs. 29%), and renal response (44% vs. 44%). Twenty-eight patients died, with no significant difference in overall survival between treatment arms. However, overall survival did favor BMDex (P = .03) among the 77 patients who were in cardiac stage II. Also, median time to second-line therapy was not reached for BMDex but was only 12 months with MDex (P less than .001).

The BMDex regimen was associated with higher rates of peripheral neuropathy (19% vs. 4% for MDex; P less than .001). Furthermore, three patients (1%) developed severe peripheral neuropathy on BMDex, while none did so on MDex. Grade 3 or higher adverse events were more common with BMDex than with MDex, but the difference did not reach statistical significance (52% vs. 40%; P = .13). There were four cardiac deaths in the first 100 days of the trial, three in the BMDex arm and one in the MDex arm (P = .31).

The European Myeloma Network sponsored the trial. Dr. Kastritis disclosed ties to Genesis, Takeda, Janssen, and Amgen.