The researchers have been focusing on thalidomide because it appears to be the most promising agent in the treatment of relapsed/refractory multiple myeloma when used alone or in combination with dexamethasone and/or chemotherapy, Dr. Corvatta said.

In a previous study, her team demonstrated a high rate and quality of response for the combination of pegylated liposomal doxorubicin, thalidomide, and dexamethasone (ThaDD) in such patients. In their current study, therefore, they compared ThaDD with the frequently used therapy for multiple myeloma, that of Thal-Dex (Haematologica. 2006 Jan;91(1):133-6).

A total of 47 patients with relapsed/refractory advanced multiple myeloma were treated with ThaDD and a control group of 47 patients were treated with thalidomide plus dexamethasone (Thal-Dex). The 2 groups were matched for age, serum beta₂-microglobulin, previous chemotherapy, and high-dose therapy.

The ThaDD regimen consisted of thalidomide 100 mg/day continuously, oral dexamethasone 40 mg on days 1 to 4 and 9 to 12, and pegylated liposomal doxorubicin (Caelyx) 40 mg on day 1, every 28 days. The Thal-Dex regimen included thalidomide 100 mg/day continuously, with oral dexamethazone 40 mg on days 1 to 4, every 28 days.

Median age was 69 years in the ThaDD group (male, 55%) and 66 years in the Thal-Dex group (male, 60%). Patient characteristics were well matched between the 2 groups for immunophenotype, light chain, nonsecretory, disease stage, median beta₂-microglobulin, median creatinine, and prior therapies. The only significant difference between group characteristics was for the higher proportion of stage III disease in the ThaDD group (P = .007).

The overall response rate (including minimal response) for ThaDD was significantly greater than for Thal-Dex (87% vs 64%; P < .01). In particular, there were significantly better qualities of response for ThaDD over Thal-Dex, respectively, for partial response or better (76.6% vs 59.6%, P = .077), very good partial response or better (36.2% vs 14.9%, P =.018), and complete plus near complete response (29.8% vs 10.6%, P = .021).

Median progression-free survival was significantly longer for ThaDD, at 22 months versus 11.5 months (36% vs 13%; P = .0008), as was the median event-free survival of 21 months versus 11.5 months (28% vs 13%; P = .0077). Overall survival was not reached in the ThaDD group, showing a trend in favour of this treatment (not reached vs 23.5 months; 52% vs 26% at 3 years; P = .0511).

The toxicity profiles for the ThaDD and Thal-Dex combinations showed significantly greater grade 3/4 neutropenia (25% vs 0%, respectively; P < .0001) and grade 3/4 infections (23% vs 0%; P < .0001). The researchers also observed a trend towards lower grades of peripheral neuropathy with the ThaDD regimen (grade 1, 19% vs 6.5%; grade 2, 6.5% vs 21%; grade 3, 2% vs 0%; P = .0510).

However, Dr. Corvatta noted that the addition of ciprofloxacin prophylaxis to the ThaDD regimen reduced infections to < 10%.

"The main message is that ThaDD in combination with chemotherapy is superior to thalidomide alone or in combination with dexamethasone," she said, and noted that the increased infections seen with ThaDD were manageable and largely preventable with adequate prophylaxis.


[Presentation title: Thalidomide-Dexamethasone Versus Thalidomide-Dexamethasone And Pegylated Liposomal Doxorubicin: A Case-Matched Study In Patients With Advanced Multiple Myeloma. Abstract 0236]

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