December 11, 2013

MMRF Newsflash from ASH 2013 - Volume 6: Highlights

MMRF Highlights from ASH 2013

Below are four key takeaways from the meeting.

Improvements and refinements to proteasome inhibitors and/or IMiDs abound

Data showing the utility and safe use of next-generation proteasome inhibitors, including Kyprolis (carfilzomib), as well as the oral agents, ixazomib (MLN9708 from Millennium) and oprozomib (from Onyx), were shown in 100+ presentations and posters. Kyprolis is increasingly being tested in newly diagnosed patients and in combination with both standard and investigational agents. Furthermore, it is highly effective (100% response rate with Revlimid-dex upfront to 60+% in the relapsed population with a variety of agents from Pomalyst to ARRY-520). Even ixazomib, which is in Phase III clinical, is being investigated – with promising results – in a variety of settings – from first-line to maintenance to salvage.

In terms of the IMiDs, Pomalyst remains one of the most active compounds available when used in combination with steroids and/or proteasome inhibitors. The Phase III trial comparing it to high-dose dex now shows a clear survival benefit. And, a sub-analysis of the data from that trial found that the drug appears to work well in patients with a chromosome 17p deletion – which is typically called “high-risk”.

More data continues to emerge on optimizing use of the first novel agent approved more than 10 years ago for multiple myeloma – Velcade. A presentation from Dr. Maria-Victoria Mateos from Spain showed that the more Velcade a patient receives, the better the outcome. With weekly dosing and sub-cut administration, patients are less likely to discontinue due to side effects. Further, a subanalysis of large trials involving Velcade showed no further increase in risk of cardiotoxcity.

Exciting new classes – particularly antibodies – are emerging

Data on SAR650984, the second anti-CD38 antibody after daratumumab, were presented publicly for the first time and did not disappoint. Though based on a very small sample, at therapeutic doses, as a single agent, response rates were similar to daratumumab in patients who had failed nearly every available option. Preliminary data on the combination of daratumumab and Rev-dex were also shown in another small population with impressive response rate (8/11 patients who had received a median of 3-4 prior treatments). Trials with these agents (including ones with SAR650984) are enrolling quickly so call our Patient Support Center (1-866-603-6628) if you might be a candidate.

Novel agents in emerging classes all of which are either in Phase I or just moving into Phase II but have produced responses in patients even at low doses included:

  • ARRY-520, a KSP inhibitor, which has been studied in an MMRC trial
  • Akt inhibitors like afuresertib, which was conducted in part through the MMRC
  • Kinase inhibitors like ibrutinib and LGH447

Finally, just prior to the start of the meeting, Novartis announced that the Phase III trial of the HDAC inhibitor panobinostat + Vel-dex vs Vel-dex in patients who had received 1-3 prior treatments, found a survival benefit for patients treated in the panobinostat combination. No further details were given but positive data bodes well for a potential 2015 FDA approval. An abstract looking at the combination in Velcade-refractory patients demonstrated that the addition of panobinostat can overcome resistance to Velcade, which is encouraging for patients who thought Velcade was out as an option and consistent with lab data.

Long-term maintenance or continuous therapy continues to be a hotly discussed topic

Prior to ASH, three studies had established improvement in progression-free survival with use of maintenance Revlimid, and two had shown survival benefits. A plenary presentation at this year’s meeting found a clear survival benefit when comparing continuous Revlimid+low-dose dexamethasone vs melphalan-prednisone-thalidomide in patients who are not candidates for high-dose chemotherapy and stem cell transplant with no increased risk of second cancers. The presenter, Dr. Thierry Facon, proclaimed that this combination represents a new standard of care for elderly patients. It is important to note that less than half of the patients randomized to continuous Rev-low dose dex were on therapy for more than two years.

Other data presented at the meeting revealed somewhat of a mixed picture. A meta-analysis from the Mayo Clinic confirmed the PFS benefits of Revlimid post-transplant, as well as longer-term use leading to deepened responses. However, the analysis also showed that benefits for those who had a very good partial response (VGPR) or better may not reap any added benefit of continuing past two years. And the French IFM group found that there was no survival advantage given an overall shorter PFS following the next line of therapy for those who had received Revlimid maintenance. However, the difference was primarily in those who went to another IMiD and at the time the trial was conducted neither Kyprolis nor Pomalyst was available, which may have made a significant difference.

Data from large groups of patients followed longitudinally are needed to address important questions and drive precision medicine

For the first time publicly, data from the landmark MMRF CoMMpassâ„  Study was presented. Already we are seeing repetition in genomic alterations – some that have been previously identified through the MMRF Genomic Initiative and other research efforts and some that are brand new. Those who attended the session were highly engaged offering unsolicited public comments about how critical it is to collect and integrate uniform longitudinal clinical and genomic data in a large sample of patients to characterize the diversity of the disease and begin to match patients with treatments that are right for them.

MMRF ASH Coverage

To see the full MMRF coverage from ASH with ongoing updates, please visit: www.themmrf.org/ash2013.

The MMRF Highlights From the 2013 ASH Annual Meeting Webcast/Teleconference will be held on Wednesday, December 18, at 1:00 PM ET! Hear our experts' perspectives on key myeloma clinical updates from ASH and learn about the latest advances in myeloma research and treatments. Register now by completing this form or calling 1-877-264-4949.