Blood cancers

Pomalidomide for myeloma: Clinical trial results vs real-world experience


In routine practice pomalidomide achieves similar response rates and progression-free survival in refractory myeloma as that reported in a landmark clinical trial, but overall survival benefits are less impressive, a review of Australian patients has concluded.

Dr Ashleigh Scott, from Princess Alexandra Hospital in Brisbane, said the benefits of pomalidomide, a third-generation immunomodulatory derivative of thalidomide, were clearly demonstrated in the MM003 study published in 2013.

The study, which included Australian patients, recognised that few effective treatments existed for patients with refractory multiple myeloma not responding to bortezomib and lenalidomide. Pomalidomide monotherapy had limited efficacy in this group, but synergistic effects were observed when combined with dexamethasone.

MM003 compared pomalidomide plus low-dose dexamethasone with high-dose dexamethasone alone, and found the combination increased PFS and overall survival.

“However, we know that patients in clinical trials are not necessarily representative of those seen in clinical practice,” he told delegates attending the combined annual scientific meeting of the Haematology Society of Australia and New Zealand, the Australia and New Zealand Society of Blood Transfusion, and the Australasian Society of Thrombosis and Haemostasis here in Melbourne.

Dr Scott and colleagues reviewed the outcomes in a ‘real-world’ cohort of 87 Australian patients treated with pomalidomide within a compassionate access program. They had received a median of five prior lines of therapy, including upfront autologous stem cell transplantation in 59%. There were 90% and 95% who were refractory to bortezomib and lenalidomide respectively, and 69% were refractory to both.

A partial response or better was obtained in 33%, and another 34% achieved a minor response or maintained stable disease.

Median PFS was 3.4 months and median OS was 7.5 months. While PFS was in line with the MM003 results (4.0 months), the OS was shorter than in the clinical trial (12.7 months).

“The worse OS likely reflects the differences between ‘real world’ and clinical trial populations,” Dr Scott said.

Among the Australian patients PFS was adversely affected by younger age (<65 years), being male, anaemia and thrombocytopenia.

“Patients younger than 65 had a higher prevalence of more advanced or refractory disease,” he said.

“Their poorer outcomes might also reflect a higher prevalence of grade III or IV organ failure, heavily-treated end-stage disease, toxicity from prior therapy, and perhaps an inability to tolerate full doses,” he suggested.

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