Dr. McCarthy,
What is the current thinking regarding treatment for high risk myeloma?
My husband was diagnosed with Stage III Kappa light chain myeloma in July of this year, has had a CR to CVDD(completing the eighth cycle currently), and is now being considered for allo transplant with unrelated donor. Could you comment on the efficacy of this treatment path vs. maintence therapy for 17p- deletion in terms of PFS and overall survival? We were told that autotransplant is not effective in high risk myeloma so should not be considered. Do you agree? Thank you.
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Re: High Risk Myeloma
Hi,
I assume that CVDD is cyclophosphamide, Velcade, doxil and dexamethasone? The chromosome 17p- is considered a negative prognostic feature of multiple myeloma for event free and overall survival. Thus, myeloma investigators have looked at a variety of approaches for this high risk disease. There is currently no "gold standard" approach. Thus, an allogeneic transplant could be considered for a patient with this abnormality. Of interest, the BMT-CTN study presented at ASH 2010 (Stadtmauer et al, Abstract 526) showed similar event free survivals (EFS) for high risk patients receiving a tandem autotransplant when compared to those receiving a tandem allo/auto transplant although they defined high risk by elevated beta 2 microglobulin and chromosome 13 deletions. There was a suggestion of a trend to better EFS in the auto/allo group but this was not statistically signficant. The IFM 05-02 study examined cytogenetics in the two arms (placebo versus lenalidomide maintenance) and found that the median progression free survivals (PFS) for patients with del(17p) were 14 months and 29 months for patients in the placebo and lenalidomide arms, respectively. (I am quoting their abstract, Avet-Loiseau et al Abstract 1944 from the ASH 2010 meeting.) We have not analyzed yet the cytogenetic data from CALGB 100104. So lenalidomide will delay progression when compared to placebo in the IFM 0502 study for multiple myeloma patients with the 17p- abnormality. It is important to realize that IFM 05-02, BMT CTN 01-02 and CALGB 100104 have not been published as peer reviewed papers in manuscript form. So keeping this in mind, an unrelated donor allogeneic transplant is one consideration but the lenalidomide maintenance data suggest that high risk patients may benefit from this approach after autotransplant.
I assume that CVDD is cyclophosphamide, Velcade, doxil and dexamethasone? The chromosome 17p- is considered a negative prognostic feature of multiple myeloma for event free and overall survival. Thus, myeloma investigators have looked at a variety of approaches for this high risk disease. There is currently no "gold standard" approach. Thus, an allogeneic transplant could be considered for a patient with this abnormality. Of interest, the BMT-CTN study presented at ASH 2010 (Stadtmauer et al, Abstract 526) showed similar event free survivals (EFS) for high risk patients receiving a tandem autotransplant when compared to those receiving a tandem allo/auto transplant although they defined high risk by elevated beta 2 microglobulin and chromosome 13 deletions. There was a suggestion of a trend to better EFS in the auto/allo group but this was not statistically signficant. The IFM 05-02 study examined cytogenetics in the two arms (placebo versus lenalidomide maintenance) and found that the median progression free survivals (PFS) for patients with del(17p) were 14 months and 29 months for patients in the placebo and lenalidomide arms, respectively. (I am quoting their abstract, Avet-Loiseau et al Abstract 1944 from the ASH 2010 meeting.) We have not analyzed yet the cytogenetic data from CALGB 100104. So lenalidomide will delay progression when compared to placebo in the IFM 0502 study for multiple myeloma patients with the 17p- abnormality. It is important to realize that IFM 05-02, BMT CTN 01-02 and CALGB 100104 have not been published as peer reviewed papers in manuscript form. So keeping this in mind, an unrelated donor allogeneic transplant is one consideration but the lenalidomide maintenance data suggest that high risk patients may benefit from this approach after autotransplant.
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Dr. Philip McCarthy - Name: Philip McCarthy Jr., M.D.
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