Multiple Myeloma

Recommendations from the Danish Myeloma Group

Staging ISS Calculator (qsmd.com)

Prognosis MGUS - The Olmsted County study (NEJM 2002). MGUS - Nice review of risk of progression (Blood reviews). These are progression curves, based on the presence of the following risk factors:
- High M protein >1.5g/dL
- Abnormal FLC ratio
- Non-IgG monoclonal protein (ie. IgM og IgA)









This risk stratification model does not take into account the amount of BM plasma cells. 0-5% is low risk, 5-0% is higher risk and >10% is, by definition, smoldering myeloma.


A similar risk stratification model was published by a Swedish group. They identified high M protein and abnormal FLC ratio (like the Olmsted County study). Interestingly, they did not find a difference in IgG and non-IgG MGUS. Instead, immunoparesis was associated with a worse outcome.

Treatment

Initial Treatment (Danish Myeloma Group)
Relapse Treatment (Danish Myeloma Group)

Elderly Patient:
This Spanish study by Dr. Mateos compared VTP to VMP (ie. thalidomide versus melphalan). Both groups did well with 80% PR or better. They used an interesting Velcade dosing, where they gave it once weekly from cycle 3 onwards (instead of twice weekly).

The Palumbo lenalidomide maintenance study was updated at ASH 2011. It seems like lenalidomide after MPR affords one year of PFS. There is no benefit in OS, but this could be from lack of maturity, use of lenalidomide in the nonmaintenance arm etc. As MM relapses tend to be severe, one year is a good increase in PFS. There was in increase in secondary malignancies, but I think this is more of a problem in MDS. MM patients have such impaired survival that an occasional secondary MDS or AML is acceptable.

The UPFRONT trial is a great trial comparing three commonly used regimens: VMP, VD and VPT. These, along with cyclophosphamide, tend to be the 4 drugs we use and the combination seems to be a little random. Perhaps not surprisingly, the three had comparable outcomes. VPT had slightly higher OR, not statistically significant, and VMP had slightly longer TTP. I worry about the neuropathy with V and T, but perhaps with subq Velcade that is less of a concern. I think it's a shame they did not include the old school arm of straight MP, excluding any novel agent from the initial treatment.

Thankfully, a fiveyear followup of the San Miguel study comparing VMP to MP was updated at ASH 2011, in a sense answering that question. V did way better than no V. The V group lived for 4.6 years, about a year longer than the no V group. Apparently, this was not true in patients with adverse cytogenetics.



Everolimus for treatment of relapsed Waldenström's. The study showed an ORR of 70%. About half of patients had problems with toxicity, so it's not free, although it works through a new mechanism (MTOR-inhibition). The ORR is similar to Velcade'd, which was 78% in a study looking at relapsed patients.

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