Can Pomalidomide Plus Dexamethasone “Rescue” Patients With Relapsed/ Refractory Amyloid Light-Chain Amyloidosis?

Patients with amyloid light-chain (AL) amyloidosis are often treated upfront with combinations of alkylating agents and bortezomib; when they don’t respond to this regimen or relapse, available active salvage options are limited.

In a phase II study published in Blood, treatment with the immunomodulatory agent pomalidomide plus dexamethasone resulted in a 68 percent response rate and a median overall survival (OS) and progression-free survival (PFS) of 26 months and 16 months, respectively.

“Our study showed that pomalidomide is effective in patients with AL amyloidosis who were previously exposed to alkylators, proteasome inhibitors, and lenalidomide. Even at an advanced stage in the course of the disease, response to rescue therapy improved survival,” lead author Giovanni Palladini, MD, PhD, from the Amyloidosis Research and Treatment Center at the University of Pavia in Italy, told ASH Clinical News. “Importantly, responses were rapid and achieved after one cycle in 53 percent of responders.”

The study included 28 patients (median age = 64 years; range = 41-80 years) who were previously treated with:

  • bortezomib (96%, n=27)
  • melphalan (75%, n=21)
  • cyclophosphamide (68%, n=19)
  • lenalidomide (25%, n=7)
  • thalidomide (14%, n=4)
  • ixazomib (14%, n=4)
  • bendamustine (11%, n=3)

All patients had a difference between amyloidogenic (involved) and uninvolved free light chain of >50 mg/L and adequate renal function (defined as an estimated glomerular filtration rate of ≥30 mL/min) and cardiac function (defined as a New York Heart Association class of <4).

Most patients were male (57%, n=16), and half had an Eastern Cooperative Oncology Group performance status of 2 (n=14), and had cardiac stage 2 function (n=14). Patients were enrolled between June 2012 and November 2013, a median of 16 months after diagnosis.

In a 3+3 dose-escalation design, three patients received pomalidomide 2 mg/day and three patients received 4 mg/day. The maximum tolerated dose was 4 mg, so the remaining 22 patients received pomalidomide 4 mg plus dexamethasone 20 mg (in the case of severe fluid retention and/or repetitive ventricular arrhythmia; n=12, 43%) or 40 mg weekly. A total of 227 cycles were delivered during the study period, with a median of six cycles per patient (range = 1-30 cycles).

After three treatment cycles, 61 percent of patients (n=17) achieved a hematologic response (primary endpoint), including partial response (PR; n=10, 36%) and very good PR (VGPR; n=7, 25%). Nineteen patients achieved a best response by cycle seven (68%; 95% CI 49-83), which included complete response (n=1, 4%), VGPR (n=7, 25%), and PR (n=11, 39%), suggesting that responses were achieved rapidly.

Hematologic response was associated with significant improvement in OS at six months compared with non-responders: 26 versus 19 months (p=0.001). Hematologic progression also predicted OS (median OS = 25 months for patients who progressed; p=0.013), as no deaths were reported in patients who did not progress.

Thirty-one grade 3/4 adverse events (AEs) were reported in 15 patients (54%); the most common of which were fluid retention (25%), infection (25%), atrial fibrillation (7%), and deep vein thrombosis (7%). The most common grade 1/2 AEs were fever (n=15, 54%), neutropenia (n=12, 43%), skin rash (n=4, 14%), and worsening peripheral neuropathy (n=2, 7%).

Dose reductions were required in nine patients treated with pomalidomide (32%) and 10 patients treated with dexamethasone (36%). Dr. Palladini and co-authors noted that “dose reductions were not associated with clinical, biochemical, and echographic markers of heart involvement.” Twenty-six patients eventually discontinued treatment, most commonly because of disease progression (n=14, 50%), followed by AEs (n=8, 29%), patient choice (n=3, 11%), and achievement of durable CR (n=1, 4%).

Two patients remained on treatment after 28 and 30 cycles, having achieved VGPR and PR, respectively. Nineteen patients (68%) died during follow-up and the remaining patients were followed for a median of 44 months. No deaths occurred in the first 100 days following treatment.

“The high rate of rapid responses suggests that pomalidomide can have a role in combination with other agents also in upfront treatment,” the authors concluded. The study’s implications, though, are limited by its small patient population and lack of a comparator arm.


Palladini G, Milani P, Foli A, et al. A phase II trial of pomalidomide and dexamethasone rescue treatment in patients with AL amyloidosis. Blood. 2017 January 27. [Epub ahead of print]