ASH Conference Post # 6 – New Myeloma Therapies

Monday at ASH seems to be the day that most myeloma papers are presented. I spent several hours listening and taking notes.

Dr. Andrzej Jakubowiak

In this study, carfilzomib was combined with Revlimid (Rev) and dexamethasone (dex) for newly-diagnosed patients. Carfilzomib was administered twice weekly, dex decreasing from 40 mg/wk.

After treatment, 100% of patients reached very good partial response (VGPR), which is simply amazing. 79% reached near-complete response (nCR) or better after 12 cycles. Side effects were low. The study is still young, but all patients are still alive. This is a very encouraging study. In the authors’ opinion, “These results compare favorably to the best frontline regimens in MM.” Who can disagree?

Dr. Paul Richardson

Dr. Richardson pointed out that two previous studies have shown that pomalidomide (pom) is active in patients for whom prior therapies have failed, including both Rev and Velcade. This new study was intended first to find the maximum tolerable dose (MTD), and then to determine progression-free survival (PFS) and overall survival (OS). Patients had lots of prior therapies.

MTD was found to be 4 mg, 3 weeks on, 1 week off.

Pom was studied as a single agent and with dex, and pom/dex was found to be quite superior to Pom alone. To quote my own doctor, “everything works better with dex.” PFS was just 4 months for these patients, whose myeloma had become quite resistant prior to this study. OS was short too, but this is no surprise with such heavily pre-treated patients.

Dr. Tomer Mark

Clarithromycin (Biaxin) is an existing approved drug which has been shown to add a significant anti-myeloma benefit when added to the combination of Revlimid and dex. So they tried this with Pom.

Enrolled study patients were resistant to at least three prior therapies, including Rev. The median number of priors was actually five, with many patients over 10. Also, many of the patients were “high-risk,” meaning that their myeloma was particularly aggressive.

Despite those odds, almost 70% of patients got a clinical benefit, and 61% were progression-free after almost seven months. This is a very impressive result!

Dr. Yi Lin

Almost ten years ago, Mayo Clinic began a study of a myeloma vaccine made with the patient’s own myeloma cells, administered after an autologous stem-cell transplant (ASCT). Today’s paper reported the final results. The vaccine provided no advantage in progression-free survival, but did provide a two-year advantage in overall survival. This is counterintuitive, and the subject of ongoing discussion.

Dr. Xavier Leleu

Study compared two different pomalidomide dosages: 4 mg for 21 days of 28 versus 2 mg for 28 of 28 days. Arms were randomized. Most patients were heavily pre-treated (many prior therapies), and many were refractory to Revlimid, or Velcade, or both.

In both arms, about 35% of patients achieved a response. The author concluded that 4 mg 21/28 was superior to 2 mg 28/28. I could not find much justification for that conclusion in the data presented, but he is the doctor and I am most definitely not. The author also stated “This study provides further evidence that pomalidomide has no cross-resistance with lenalidomide …”. I’m not quite certain that his data quite supports that far-reaching conclusion either, but I hope it’s true.

Dr. Ravi Vij

Dr. Vij reported on an early study of carfilzomib as a single agent (no dex). Patients had never been treated with Velcade, but had relapsed from as many as four prior treatments. Twelve cycles of carfilzomib were administered. Roughly 60% of patients had a good response.

Carfilzomib has been submitted for FDA approval.

Dr. Paul Richardson

Panobinostat is an oral pan-deacetylase inhibitor which can create defective proteins within a cell (my interpretation). Velcade can prevent the cell from clearing proteins like that, and the two can work together to persuade the cell to die.

Patients were heavily pre-treated, and still the treatment of Panobinostat/Velcade/dex proved effective for about 50% of them.

Perifosine plus Velcade and dex in heavily pre-treated patients, including patients for whom Velcade has failed. Perifosine attacks tumors in a new way, and was known to be synergistic with other drugs. It is an Akt Inhibitor. They wanted to find the MTD, and then the efficacy.

41% of patients achieved a useful response, but some subgroups were much higher. Median OS was 25 months, and 37 months for people who responded well. This is evidence that perifosine can overcome resistance to Velcade in some people. There is now a Phase III trial recruiting.

Dr. Shaji Kumar

MLN9078 ia the first oral proteasome inhibitor to be evaluated for treatment of MM. This study was to determine the maximum-tolerated dose (MTD) of MLN9078 as a single agent. Patients had at least two prior failed therapies.

Conclusion: Dosage has been established, and the drug clearly seems to work, even as a single agent, and caused little or no neuropathy. A doctor near me offered the opinion that MLN9078 shows a great deal of promise and, eventually, might even compare with carfilzomib. If I were on Velcade, getting infusions in a clinic, I would much prefer to take this drug instead, at home, and also avoid the risk of painful neuropathy.

This is the last post from ASH. We’re home in Minnesota now, and soon heading off to Mayo Clinic for my regular 28-day checkup and then off to a marathon in Delaware. State # 42 if all goes well.