Australian clinicians report on real world use of bortezomib in elderly MM patients

Real world experience with early bortezomib therapy in multiple myeloma in Australia suggests that it is used in patients who are older and more vulnerable than those in clinical trials.

A retrospective review has reported data from 74 patients at three Queensland hospitals who had newly diagnosed multiple myeloma ineligible for autologous stem cell transplantation who were given their first dose of bortezomib between 2012 and 2016.

Outcomes were compared to those from pivotal RCTs VISTA and GIMEMA.

The study found the Queensland patients were older than those in the RCTs (75 v 71 years), had high cytogenetic risk (36% v 30% in GIMEMA), worse renal impairment (35% v 6-9%), and more comorbidities at baseline.

The local patients received a lower median cumulative dose than in the clinical trials (29.6 v 36.6 mg/m2 in VISTA). Most patients (60.8%) had at least one dose delay or cancellation and 53% discontinued their treatment mostly due to toxicity.

Outcomes such as PFS (17.7 v 21.7-24.8 months) and OS (40.7 v 56.4-60.6 months) were worse in the Queensland patients than in the RCTs.

“Multivariate analyses indicated that age ≥80 years (HR 2.72; 95%CI, 1.3-5.67) and moderate to severe pulmonary disease (HR 3.57; 95%CI, 1.57-8.13) were significant risk factors for worse OS,” the study authors said.

Older age ≥80 years (HR 2.74; 95%CI, 1.45-5.21) and worse disease as indicated by higher ISS (HR 1.8; 95%CI, 1.04- 3.08) were significant risk factors for worse PFS.

The study authors said the patients nevertheless achieved good response rates that were similar to key clinical trials despite later having a shorter OS and PFS.

“We attribute the lower OS and PFS outcomes to patient factors rather than disease response to bortezomib-based therapy,” they wrote.

Co-author and haematologist Associate Professor Peter Mollee, from the Princess Alexandra Hospital, told the limbic the findings were not particularly surprising.

“The problem with clinical trials is that they exclude all these patients. Myeloma is one of the few diseases where there are elderly trials but even in these trials, patients are excluded because of comorbidities.”

“And what we really need is trials that have specifically got frailty-adapted dosing to work out how to deliver these drugs most effectively but with the least side-effects to elderly frail patients.”

“It’s no good having a drug which will work in a small, healthy proportion of the [myeloma] population and you remain uncertain whether it really has the same benefit in the majority of patients.”

He said the finding that lung disease was a strong predictor of mortality meant clinicians should pay close attention to infection prophylaxis, vaccination and minimising the risk of pneumonia.

“We know that patients with multiple myeloma are at increased risk of infection, whether you treat them or not, and patients with myeloma are particularly at risk of respiratory infections. They have macroglobulinaemia so they are particularly predisposed to pneumococcal and haemophilus infections,” he said.

The study authors also noted that the costs of bortezomib were substantial with an average cost per patient of AU$40,154.

The PBS cost incurred after four years of subsidy was AU$32.1 million, three-fold higher than the manufacturer’s initial estimates.

Associate Professor Mollee said the anomaly possibly related to the speed of uptake of a new therapy.

Originally published on The Limbic