December 10, 2013

MMRF Newsflash from ASH 2013 - Volume 4

Welcome to our fourth report on the 2013 American Society of Hematology (ASH) Annual meeting, featuring many posters on multiple myeloma.

Highlights from yesterday morning’s early presentations included:

Relapsed refractory disease

  • Dr. Voorhees from the University of North Carolina, Chapel Hill, presented the results of a Phase I/II trial of the AKT inhibitor, afuresertib, combined with Velcade and dexamethasone. Phase II is ongoing, with 37 patients enrolled in part 2. Patients had a median of 3 prior lines of therapy (82% had prior proteasome inhibitors and 96% had prior IMiDs). The most common adverse events were fatigue, diarrhea, nausea, and constipation. The overall response rate was 65%, including many responses in Velcade refractory patients. Eight Multiple Myeloma Research Consortium (MMRC) sites participated in this trial.
  • Dr. Martin of the University of California, San Francisco presented the preliminary results of a Phase I study of the SAR 650984, a new anti-CD38 monoclonal antibody, in CD38-positive hematologic malignancies including multiple myeloma patients. SAR650984 is also being evaluated in an MMRC trial in combination with Revlimid-dex, and is in the same class as daratumumab. So far, 39 patients previously treated with a median of 6 prior therapies have been treated at various doses. The results are early, but patients have experienced very low rates of toxicities, the most common of which were fatigue, nausea, fever, cough and anemia, and were mostly mild. There have been no Grade 3-4 hematologic toxicities, which is promising given the side effects often seen with proteasome inhibitors and IMiDs. 31% of patients have responded so far to clinically meaningful doses, and there have been two complete responses.
  • Preliminary results of a Phase II trial of the KSP kinase inhibitor, ARRY-520 (filanesib) were also reported. Filanesib was given as a single agent or in combination with low-dose dexamethasone. Patients enrolled in the 2 treatment groups had a median of 6 or 8 previous therapies, and were refractory to their last line of therapy. Hematologic toxicities included neutropenia, thrombocytopenia, and anemia. The primary reason for discontinuation was progressive disease, with few patients discontinuing due to toxicity. The overall response rate was 16% for filanesib alone and 15% for filanesib plus dexamethasone. Interestingly, patients who did not respond to filanesib therapy expressed high levels of a protein called alpha-1 acid glycoprotein (AAG), suggesting that AAG is a marker for those who will not respond to this agent. Filanesib is also being studied with Velcade-dex and Kyprolis-dex (both posters were presented on Saturday); the MMRC is part of the Velcade-dex study.
  • Dr. Schey of King's College London, London, presented a trial evaluating the dose of bendamustine combined with thalidomide and dexamethasone in relapsed/refractory patients. This regimen showed a 55.6% response rate in the primary population of patients, with the most common toxicities being neutropenia, thrombocytopenia, and anemia. This is further evidence that bendamustine may be an option for some individuals, particularly as, in the US, it is approved for a different blood cancer and may be used off-label.
  • Dr. Dimopoulos of Greece presented a final analysis of the Phase III, MM-003 trial comparing low-dose dexamethasone with Pomalyst to high-dose dexamethasone in relapsed refractory disease. The analysis showed that high-risk cytogenetics, including t(4;14) and del17p-, did not impact median progression-free survival for patients receiving Pomalyst with low-dose dexamethasone.

Newly diagnosed disease

  • Dr. Sonneveld of the Netherlands presented an extended follow up of the HOVON-56/GMMG-HD4 trial of Velcade Induction and maintenance treatment in newly diagnosed patients. The follow up after 74 months was reported. Velcade treatment during induction and maintenance improved complete responses and as well as progression-free and overall survival, and rates of second primary malignancies were low.
  • Dr. Attal of France presented a follow up study of the IFM 2005-02 trial of Revlimid maintenance after stem cell transplantation. The new analysis found that Revlimid effectively prolonged progression-free survival after transplantation, but this has not yet translated into improved overall survival as patients in the Revlimid arm of the trial who then went on subsequent therapy experienced a shorter progression free survival and overall survival on their next line of therapy as opposed to those on the placebo arm.
  • Dr. Singh from the Mayo Clinic, Rochester, MN, presented a meta-analysis of randomized trials of lenalidomide maintenance therapy after induction therapy alone or post-autologous stem cell transplant. This analysis indicated significant improvement in progression free and modest improvement in overall survival with lenalidomide maintenance. An increased risk of grade 3-4 toxicities, including second primary malignancies was also indicated.

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.