Biochemical Progression of Stage II High-Risk Multiple Myeloma - Episode 3

Consolidation Autologous Transplant for Myeloma

Ajai Chari, MD:If we agree that triplet therapy is probably optimal as induction therapy, then the question is, if these responses are so good, what is the role of transplant in 2017? That question was kind of hard to answer. We all had a feeling that if somebody had such a great response, what was the role of transplant? Again, we need data. Luckily, the IFM/Dana-Farber (IFM/DFCI) study has really helped us understand this. This study took everybody with newly diagnosed symptomatic myeloma that was transplant eligible, and gave them 3 cycles of RVD (bortezomib, lenalidomide, and dexamethasone) as induction therapy. Everybody had cyclophosphamide mobilization, and then half were randomized to transplant with RVD consolidation and lenalidomide maintenance. In contrast, the control arm had, after collection, 5 cycles of RVD consolidation and then a year of lenalidomide maintenance.

In this study, we found that the depth of response was better with transplant consolidation, and the PFS (progression-free survival) was significantly prolonged by almost 14 to 15 months. It didn’t seem to matter because one might think, “Well, perhaps these were only for people who didn’t have that great depth of response?” But, this was regardless of age, regardless of risk, and regardless of depth of response to induction therapy. So, if we take that data at face value, it suggests that early transplant is not a bad option, and it may result in better outcomes. The limitation, though, is that an overall survival was not different—it was about 43 months of follow up. That’s important because we now know that median overall survival in myeloma (particularly for standard risk and favorable risk) can be well over 7 to 10 years. This follow up may not be long enough to understand the OS (overall survival) benefit.

The other important caveat is that this was the French version of the study, where lenalidomide maintenance was terminated at 1 year. The American counterpart to this uses lenalidomide maintenance until progression. It’s possible, then, that we may see less difference in PFS if we continue lenalidomide maintenance until progression. So, the jury is out on that approach. But, in 2017, what do we tell our patients? We present them this data that consolidating that first induction therapy with a transplant seems to result in better outcomes. Is it mandatory? Perhaps not, since there’s not yet an OS difference. However, I think that most transplant centers and physicians would strongly encourage early transplant.

Based on the data from the IFM/DFCI study, which supports early transplant, this patient, who is 61 years old, is transplant eligible, seems to have had a good response to therapy, and is someone in whom there shouldn’t be any problems collecting stem cells for, would likely be a good candidate for both stem cell harvesting and proceeding with stem cell transplantation as a consolidation modality.

Transcript edited for clarity.

Biochemical Progression of Stage II Myeloma

July 2011

  • A 61-year-old Caucasian female was diagnosed with stage II multiple myeloma
  • Genetic testing showed t(14:16)
  • At the time she was treated with lenalidomide, bortezomib, and dexamethasone (RVD) induction therapy followed by autologous stem cell transplantation
  • She achieved a near complete remission with RVD and transplant
  • Based on her high-risk cytogenetics, the patient was placed on lenalidomide maintenance therapy

August 2016

  • On routine follow up, the patient reports having mild fatigue but continues to work full-time; she has grade 1 neuropathy
    • M-protein, 1.3 g/dL
    • SFLC, kappa, 150 mg/L
    • Hb, 10.3 g/dL
    • Creatinine, 1.3 mg/dL