June 2, 2012
MMRF Newsflash from ASCO - 1
The MMRF team is on site at the 2012 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago and is pleased to share with you highlights from key sessions over the next 3 days.
This morning, a myeloma poster session highlighted new data from the investigational oral proteasome inhibitor MLN9708; additional data for the investigational proteasome inhibitor carfilzomib; data from several other treatment regimens; and a look at second primary malignancies.
Highly anticipated data from two studies of the investigational oral proteasome inhibitor MLN9708 were presented today. One was a phase 1/2 study in combination with Revlimid and standard-dose dexamethasone for previously untreated patients (led by Dr. Paul Richardson from the Dana-Farber), and a phase 1 study as monotherapy in the relapsed/refractory setting led by Dr. Shaji Kumar of the Mayo Clinic. Both studies used a once-weekly dosing schedule and both confirmed a maximum tolerated dose (MTD) of 2.97 mg/m2. The recommended phase 2 dose was 2.23 mg/m2 according to the overall safety and efficacy results of the phase 1 portion of the combination study. A twice weekly schedule is also being investigated using a 2.0 mg/m2 dose. Dr. Sagar Lonial from the Winship Cancer Institute at Emory University will present results using this schedule for patients with relapsed/refractory disease at a myeloma oral presentation tomorrow.
The phase 1 monotherapy study had a promising adverse event (AE) profile in 52 total patients. No significant neuropathy was observed. The most common AEs were transient thrombocytopenia (with platelet counts recovering towards baseline levels following dosing in each cycle) and gastrointestinal symptoms, requiring study discontinuation for 2 patients. The phase 1/2 combination study reported an overall response rate of 98% in 46 patients, with a complete response seen in 26% and a very good partial response or better in 39%. The drug appeared generally well-tolerated in this study as well, with the most common AE being rash, none of which required drug discontinuation. One patient experienced a grade 3 peripheral neuropathy (the first peripheral neuropathy greater than Grade 2 seen with this drug) at a dose greater than the recommended phase 2 dose. Based on these data, a global, randomized, phase 3 study of this combination compared to Revlimid and dexamethasone alone for relapsed/refractory MM has been registered at www.clinicaltrials.gov (NCT01564537) and enrollment will begin soon.
One poster on carfilzomib was presented today (with Dr. David Siegel from the John Theurer Cancer Center at Hackensack University as first author). It described a sub-analysis of 266 patients refractory or intolerant to both Velcade and immunomodulating agents (thalidomide or Revlimid), who were enrolled in PX-171-003-A1, a phase 2b monotherapy study of patients who had relapsed/refractory myeloma that was conducted in collaboration with the Multiple Myeloma Research Consortium (MMRC). These patients were heavily pre-treated, with 82% receiving at least 4 prior therapies. The overall response rate was 22.9% (15.4% for 169 patients refractory to both Velcade and Revlimid).
Another two posters described analyses of second primary malignancies (SPMs) following myeloma treatment. One analysis of 1175 patients confirmed other recent analyses of SPMs in multiple myeloma, demonstrating that the rates of SPMs were as expected for this patient population, although follow-up was relatively short at just over 12 months. The incidence of SPMs was similar in patients under 65 versus 65 and older, and no correlation was seen according to different treatment regimens. In contrast, a study of 869 patients receiving an autologous stem cell transplant at the City of Hope revealed what was described as a high incidence of SPMs, at a cumulative 10-year incidence of 15.9% (primarily solid tumors), with a trend towards increased risk in patients receiving thalidomide. There were insufficient numbers of patients receiving Revlimid for any correlations to be seen, but the authors suggested that there may be a class effect. Clearly the issue of SPMs in myeloma requires further long-term analyses, though, most believe that, based on the current data, the survival advantage that has been seen in one study and the delayed disease progression are benefits that outweigh any potential risks. Long-term follow-up will continue.
Stay tuned for additional updates including a summary of oral abstracts being presented tomorrow morning!