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Report from ASCO 2012: New Results in Frontline and at Relapse
Dr. Brian Durie highlights important myeloma news from the annual meeting of the American Society of Clinical Oncology (ASCO)

Although the annual meeting of the American Society of Clinical Oncology (ASCO)—which ended Tuesday in Chicago—does not have the number or scope of abstracts presented at the meetings of the American Society of Hematology (ASH), there were nonetheless several important presentations of interest to members of the myeloma community.

Three presentations in the frontline setting demonstrated the remarkable benefits with Carfilzomib combinations:

  • Abstract 8009 from the French IFM group summarized results with carfilzomib plus melphalan and prednisone (CMP), which can be compared with the extensive prior data with Velcade (V) MP (VMP). The objective response rate (ORR) (>50% regression) with CMP was an impressive 92% (versus 71% with VMP), with 42% having > a very good partial response rate (VGPR) with CMP.

  • Abstract 8010 from the Mayo Clinic group in Scottsdale, Ariz., looked at a new regimen called CYCLONE, incorporating carfilzomib, cyclophosphamide, thalidomide and dexamethasone. At the early phase of this study all patients had responded, with 83% achievingVGPR, with a combination that appeared to be reasonably well tolerated.

  • Abstract 8011, from Dr. Andrzej Jakubowiak of the University of Chicago Medical Center, and colleagues, provided follow-up data utilizing his frontline combination of carfilzomib and lenalidomide (Revlimid) plus dexamethasone. Emphasis was placed upon the fact that 42% of patients achieved stringent CR. Progression-free survival (PFS) was 97% at 12 months and 92% at 24 months, indicating ongoing treatment benefit. In contrast, the Mayo Clinic team from Rochester, Minn. (Abstract 8096), detailed the longer-term outcomes with the two-drug combination of lenalidomide (Revlimid) plus dexamethasone as first therapy. Tracking 286 consecutive patients, the median survival was 8 years, reflecting both induction and follow-up therapy.

Clearly, it will take some time to assess which is the ideal combination to achieve both excellent early results, acceptable toxicity, and the best longer-term benefit.

In the relapse/refractory setting many single agents and combinations were evaluated. Of the single agents, both pomalidomide and carfilzomib demonstrated expected efficacy, with ORRs of about 30% or better. It is hoped that both will be approved by the FDA soon (watch for this news in upcoming issues of the Myeloma Minute).

Of the newer agents, both elotuzumab and MLN 9708 (an oral proteasome inhibitor) continued to show promising results.

Among agents at an early stage of development, results were rather disappointing. Obatolclax (anti-BCL-2; Abstract 8013); siltuximab (anti-IL-6; Abstract 8018); and daratumumab (anti-CD38; Abstract 8018) showed limited evidence of efficacy. Daratumumab was the only one of the 3 to produce any single agent responses at the partial response ( PR ) level.

In other abstracts, a retrospective analysis of 841 consecutive patients from the City of Hope (Abstract 8038) showed that the primary correlates for development of second primary malignancies (SPMs) were older age (> age 55 years) and non-Hispanic white race (P=0.01). There were several interesting abstracts that will undoubtedly give rise to further research. Among them, Abstract 8040 suggested that t(11;14), commonly thought to be a “good-risk” translocation, may have a negative impact related to ASCT; Abstract 8097 presented results of a large analysis demonstrating a different pattern of disease and outcomes in Asian patients and Abstract 8088 presented inconsistencies in systems used to assess risk progression in smoldering myeloma.

The IMF is summarizing all of the important myeloma abstracts and has also interviewed the lead investigators for the IMF web site. Thus, further details will be available soon. As always, new data are moving the field forward and helping to identify the best approaches to diagnosis and therapy for myeloma patients worldwide. Stay connected to the Myeloma Minute via our Myeloma Post iPad app or directly on the website (myeloma.org) to get all the latest information.

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