June 5, 2011

Updates from Day 2 at ASCO

Welcome to day 2 of live coverage of the ASCO Annual Meeting in Chicago. Today was a big day for multiple myeloma!

First, a session of oral abstracts – those deemed by the scientific organizers to have the greatest impact on patient care - dedicated exclusively to myeloma discussed critically important topics: the risk of second primary malignancies (SPMs) following Revlimid treatment; the role of bisphosphonates in myeloma; and studies of new drugs in development. Three speakers discussed the potential risk of SPMs following Revlimid treatment. This issue was first brought up at last year’s annual meeting of the American Society of Hematology (ASH), in which three randomized phase III studies—MM-015, IFM 2005-02, and CALGB 100104—reported SPMs in a small number of patients receiving Revlimid maintenance. The common feature among all of these trials, as opposed to other trials where SPMs have not emerged as a potential issue, is that patients first received high-dose melphalan or the MPR regimen.

At today’s session on SPMs:

  • Dr. Antonio Palumbo, principal investigator for MM-015, described a retrospective analysis of approximately 1800 patients from nine studies of various myeloma therapies. Following a median of 30 months of follow-up, Dr. Palumbo observed a 7% increased risk of SPMs in patients receiving Revlimid maintenance therapy.
  • Dr. Adriana Rossi and Dr. Ruben Niesvizky reported similar data from retrospective analyses; Dr. Rossi analyzed continuous therapy using the BiRD regimen (clarithromycin, Revlimid, and dexamethasone) after almost six years of follow-up, and Dr. Ruben Niesvizky analyzed the MM-009 and MM-010 studies of Revlimid and dexamethasone. Neither found any increased risk of SPMs. Importantly, though, neither regimen included melphlan.
  • All three presenters believed that, at present, the benefits of Revlimid therapy, overall as well as in the maintenance setting, outweigh any potential risk of SPMs. Nevertheless, it is important for patients to discuss with their doctor the risk of SPMs, as is the case for all potential adverse effects of treatment.

Next, two speakers discussed the role of bisphosphonates in myeloma treatment, using data from the MRC Myeloma IX Trial that compared Zometa (zoledronic acid) and clodronate with chemotherapy for patients with newly diagnosed myeloma.

  • Dr. Gareth Morgan reported that patients with and without bone disease at presentation benefited from Zometa; following almost four years of follow-up, both groups of patients had a reduced incidence of skeletal-related events (SREs). Improvements in progression-free survival were also seen compared to the clodronate arm, but these were limited to patients with bone disease.
  • Dr. Faith Davies reported that patients continued to see a reduced incidence of SREs at least up to three years of Zometa based on a landmark analysis, and that overall survival benefits increased over time.
  • Both authors recommended changes to the current guidelines for bisphosphonate therapy, which currently recommend two years of treatment for patients with bone disease only.

In a discussion following these talks, Dr. Roodman expressed his view that it was premature to change current practice regarding the use of bisphosphonates as no survival benefit was seen in patients without bone disease in this study, and the risk of osteonecrosis of the jaw (ONJ) remains a significant consideration.

Finally, three speakers discussed results of studies in the relapsed and/or refractory setting of novel antibodies in development for the treatment of multiple myeloma:

  • Dr. Noopur Raje described a phase I study of LY2127399, an anti-BAFF antibody, whose preclinical development was supported by grant funding from the MMRF, combined with bortezomib. This is an early trial but the combination is worth watching given its preliminary safety and efficacy profile.
  • Dr. Jesus Berdeja described a phase I study of lorvotuzumab mertansine (IMGN901) in combination with Revlimid and dexamethasone. Similar Dr. Raje’s presentation, while these are very preliminary results, they looked promising.
  • Dr. Philippe Moreau from France reported updated data from a phase I/II study of elotuzumab, which has been studied in MMRC-facilitated trials, combined with Revlimid and dexamethasone in relapsed patients. This study has large patient numbers and demonstrated an impressive 82% response rate; a median progression-free-survival rate that has not been reached as of nine months of follow-up; and a manageable toxicity profile. A phase III study of this combination is underway in relapsed patients.

In his discussion of these presentations, Dr. Nikhil Munshi expressed enthusiasm for the future of monoclonal antibody therapy in myeloma and excitement regarding the elotuzumab phase III study, noting that “we may have more than one ‘rituximab’ (Rituxan – which transformed the care of patients with non-Hodgkin lymphoma) for myeloma” in the future.

Immediately following this oral session, the MMRF interviewed Drs. Rafael Fonseca and David Roodman, who provided a fascinating and informative discussion of what these and other presentations at ASCO mean for patients and their families. Stay tuned for the MMRF Myeloma Update webcast of these interviews, and for our final ASCO update tomorrow!