ASCO 2012 – Blog Post # 2

ASCO deals with all cancers, not just blood cancers, and many sessions are taking place at once. However Sunday, June 3, was “Myeloma Day.” That session ran from 8:00 am to 11:00 am and included 12 talks. Some were rather researchy (new word) but several were of immediate interest.

Carfilzomib/Revlimid/dexamethasone (dex):

At the ASH conference in December, Dr Andrzej J. Jakubowiak had showed that the combination of carfilzomib, Revlimid, and dexamethasone was extremely effective for newly-diagnosed patients. Today Dr Jakubowiak showed that extended treatment produces even better responses, with over 64% achieving a “stringent” complete response, where no myeloma cells can be identified by the best measurement techniques. Further, responses appear to be very durable over time.

Bendamustine/Velcade/dex:

Dr Philippe Rodon of France described a study demonstrating that bendamustine, an alkylating agent, can help some heavily-pretreated patients when added to a Velcade/dex regimen. This may be true even when the patient’s disease no longer responds to Velcade/dex.

Panobinostat/Velcade/dex:

Dr Melissa Alsina described a Phase II study showing that panobinostat, added to a Velcade/dex regimen, can rescue some patients whose myeloma has proven resistant to most treatments, including Velcade/dex. The overall response rate was 31%.

Carfilzomib versus Velcade:

Both of these drugs are proteasome inhibitors – they target a particular part of the cell, especially plasma cells. The two drugs have not been compared in a head-to-head study, but Dr Robert Orlowski did his best to compare them anyway, using data from comparable studies. A study of carfilzomib/melphalan/prednisone, and another of Velcade/melphalan/prednisone showed almost equal efficacy, though Velcade caused more neuropathy. Carfilzomib is looking good, but all studies of Velcade have used intravenous Velcade. Modern comparisons should use sub-Q Velcade, and once-weekly at most.

Cyclophosphamide/carfilzomib/thalidomide/dex:

Ouch. Dr Joseph Mikhael presented the results of this 4-drug study, with newly-diagnosed patients. It achieved a high response rate, 83% “very good partial response,” but at the cost of many Grade 3 toxicities. Grade 3 is severe enough to significantly interfere with a patient’s health or comfort, and generally requires a dosage reduction. Dr Orlowski suggested dropping the thalidomide and trying just the other three.

Bisphosphonate Therapy:

Dr Gareth J Morgan described studies showing that Zometa, compared with Aredia, results in a significant improvement in overall survival (!).
Zometa causes more osteonecrosis of the jaw (ONJ), however, almost 4% reporting it, compared with 1% for Aredia. Most of the ONJ occurs in the first 36 months of treatment. ONJ appeared to be less in patients being treated with thalidomide. Some of the ONJ events seemed to be related to dental procedures.

Pomalidomide/dex:

Dr Ravi Vij described a study comparing showing that pomalidomide can be effective in a population of heavily-pretreated patients whose myeloma is resistant to both Velcade and Revlimid. In one arm of the study, patients got pom/dex, while the other arm received pom alone. Response rate was 30% for the dex arm, and 9% for the pom-only arm. The difference in time of survival was not as dramatic. Bottom line – take your pom with dex. Sorry about that.

MLN9708:

This is an exciting new proteasome inhibitor, like Velcade and carfilzomib, but can be taken at home as a pill. Dr Sagar Lonial described a Phase I study with heavily-pretreated patients. A Phase I study is designed to find the maximum tolerable dose of a drug, and determine other safety factors, rather than to determine the drug’s treatment efficacy. However, many of these patients did achieve good responses or stable disease. There was very little peripheral neuropathy.