Today was the third day of the American Society of Clinical Oncology (ASCO) annual meeting, and the morning was filled with oral presentations about important myeloma-related studies. Most of the talks were about potential new anti-myeloma drugs.
This update summarizes the presentations about panobinostat, obatoclax, Treanda (bendamustine), and MLN9708 (ixazomib), which are all being developed as potential multiple myeloma treatments. In addition, the update includes a recap of a presentation about the safety of long-term bisphosphonate use.
An update from earlier today summarized today’s presentations about carfilzomib (Kyprolis) and pomalidomide, both of which have been submitted to the U.S. Food and Drug Administration for potential approval as new myeloma treatments.
Panobinostat
One of the morning presentations was given by Dr. Melissa Alsina from the H. Lee Moffitt Cancer Center in Tampa, Florida. Dr. Alsina presented a Phase 2 study of panobinostat in combination with Velcade (bortezomib) and dexamethasone (Decadron).
The study included 55 patients with relapsed and Velcade-refractory (resistant) multiple myeloma, with a median of four previous lines of therapy. Almost all of the patients also had been treated with Revlimid (lenalidomide) in the past.
Overall, 31 percent of the patients responded to the panobinostat combination, with 2 percent achieving a near complete response and 29 percent a partial response.
The most common severe side effects were low platelet counts, fatigue, low red blood cell counts, pneumonia, low white blood cell counts, and diarrhea. Peripheral neuropathy — which is pain, tingling, or loss of feeling in the extremities — was experienced by 31 percent of the patients, but almost all cases were mild or moderate.
The panobinostat trial results were reviewed by Dr. Asher Chanan-Khan of the Mayo Clinic in Jacksonville, Florida, in a presentation that also took place during this morning’s session.
Dr. Chanan-Khan described the results as interesting. However, he does not feel he can yet draw any conclusions about panobinostat’s role as a myeloma treatment based on these, or previous, trial results for the drug.
For further details, see the slide deck (PDF) for Dr. Chanan-Khan’s presentation, which he has made available as a courtesy to The Beacon’s readers.
Obatoclax
Dr. A. K. Stewart from the Mayo Clinic in Arizona then presented results from a Phase 1 study of obatoclax in combination with Velcade for the treatment of relapsed multiple myeloma (abstract).
The study included 11 patients, 10 of whom were evaluated for response. To take part in the trial, patients had to have had at least one previous line of therapy. However, patients in the trial typically had relatively advanced myeloma, with the median time since first diagnosis being 4.7 years.
Among the 10 patients who could be evaluated for a response, 40 percent achieved a partial response and 10 percent achieved a minimal response.
The side effect profile of the combination, however, was quite negative. In addition to blood-related side effects often seen with myeloma treatments, the combination also brought about unusual, and severe, neurologic side effects, such as extreme sleepiness or euphoria.
For this reason, Dr. Stewart said that he and his colleagues have no plans to conduct further studies of obatoclax as a potential myeloma treatment.
For further details, see the slide deck (PDF) for Dr. Stewart’s presentation, which he has made available as a courtesy to The Beacon’s readers.
Treanda
Next, Dr. Philippe Rodon from General Hospital in Blois, France, presented results from a Phase 2 study of Treanda in combination with Velcade and dexamethasone in elderly myeloma patients (abstract).
The study included 73 patients over 65 years of age who had relapsed or were refractory to treatment after one previous line of therapy. Patients could not take part in the study, however, if they had been previously treated with Velcade or received a stem cell transplant.
Overall, 58 percent of patients responded, with 11 percent achieving a complete response, 12 percent a very good partial response, and 34 percent a partial response.
The most common severe side effects were low white blood cell counts, low platelet counts, sepsis, and gastrointestinal upset. Four patients died during the trial due to sepsis, and one patient died as a result of kidney failure.
The results of the Treanda trial also were discussed by Dr. Chanan-Khan during his review presentation at this morning’s session. Dr. Chanan-Khan said that, in his opinion, the Treanda combination showed significant toxicity, yet the efficacy of the combination was not much better than Velcade alone combined with dexamethasone. Therefore, he would not be inclined to use the Treanda combination in patients after just a single previous line of therapy.
As a courtesy to The Beacon’s readers, Dr. Rodon has made his presentation available for download and viewing.
MLN9708
Later during the morning session, Dr. Sagar Lonial from the Emory Winship Cancer Institute presented results from a Phase 1 study of MLN9708 as a single-agent treatment (abstract).
This study included 58 patients with relapsed and refractory multiple myeloma. The patients had a median of four previous lines of therapy, and the majority of trial participants had previously been treated with Velcade and either Revlimid or thalidomide (Thalomid).
As compared to the study presented during Saturday’s poster session in which MLN9708 was administered once a week (see related Beacon news), this study tested MLN9708 administered twice a week.
Among the 53 patients evaluated for response, 11 percent responded to MLN9708 therapy. Specifically, 2 percent achieved a stringent complete response, 4 percent achieved a very good partial response, and 6 percent achieved a partial response.
The most commonly observed serious side effects were low platelet counts, low white blood cell counts, fatigue, and rash. Additionally, 11 percent had mild or moderate peripheral neuropathy.
Bisphosphonates
One of the last presentations during this morning’s session was given by Dr. Gareth Morgan from the National Cancer Research Institute in London. Dr. Morgan presented long-term efficacy and safety data for bisphosphonate therapy (abstract), based on updated results from the well-known “MRC Myeloma IX” clinical trial.
The results are based on data from 1,960 myeloma patients who received anti-myeloma therapy along with either Zometa (zoledronic acid) or Bonefos (clodronate). Both of these drugs belong to the class of bone-building treatments known as bisphosphonates. However, Bonefos is not sold in the United States.
At a median follow-up of 5.8 years, patients who received Zometa had improved progression-free and overall survival relative to those who received Bonefos.
Dr. Morgan stated that long-term bisphosphonate therapy was generally well tolerated. However, patients receiving Zometa were at higher risk of developing osteonecrosis of the jaw (ONJ), a condition that is associated with a loss of blood supply to the jaw, causing the jawbone tissue to die.
Among the patients treated with Zometa, 3.7 percent developed ONJ, compared to 0.5 percent of the patients treated with Bonefos.
Dr. Morgan and his colleagues found that patients typically developed ONJ between 8 and 30 months of bisphosphonate therapy, with the risk ceasing around 3 years. They also found that patients treated with thalidomide had a lower risk of developing ONJ.
Myeloma-related presentations from Day 4 of the 2012 ASCO annual meeting also will be summarized in daily updates to be published tomorrow. Additional coverage of key research results from the meeting will continue throughout the rest of the week in individual, topic-specific news articles.
For all Beacon articles related to this year’s ASCO meeting, see The Beacon’s full ASCO 2012 coverage.