Autologous Transplantation for High-Risk Myeloma

C. Ola Landgren, MD:Transplantation is the terminology we use for the use of melphalan chemotherapy. Patients who receive melphalan chemotherapy, they collect their stem cells prior to the delivery of melphalan and then they get back a subset of the collected stem cells. And the intent of the stem cells is to speed up the recovery after chemotherapy. So, really, when we talk about autologous transplantation, we are kind of bending the words here. It is really chemotherapy. The cells have no therapeutic implications.

This was developed in the 1980s and fully implemented around the world in the 1990s. We still think about this as a therapeutic option to consider almost as a default for newly diagnosed patients. I think the field is gradually changing, and with access to better drugs, a lot of patients reach very good responses with combinations and they’re questioning the use of transplantation. So, on one hand, we are facing the fact that the transplant is under question as a default therapy. On the other hand, we are getting better and better at taking care of our patients. Patients who previously were considered to be candidates for transplant, they were primarily younger patients. So, a better standard of care, better ways to monitor patients. The transplanters are open to transplant older and older patients. So, on that note, older patients are also considered as transplant candidates.

In this particular case, we have a 74-year-old lady who presents with myeloma. She has renal failure. She had a history of cardiovascular disease. Most likely if she gets combination therapy, I would think that the kidney failure can be reset and hopefully could be completely normalized. There is a possibility that she could have a little bit of a residual renal insufficiency, but that probably would not really impact her overall situation and she probably would not have any symptoms of that.

So, let’s say we give her 4 or 6 cycles of CyBorD (cyclophosphamide/bortezomib/dexamethasone) as we discussed before. Would she now be a candidate for transplantation? I do think if she recovers from her kidney, she probably is a candidate for transplantation if she would like to do that. She could collect her stem cells and she could go forward with the transplantation. But I also think if the patient chooses to not do a transplantation and she obtains a good response with a combination therapy, she would go straight to maintenance therapy—but that would also be a reasonable approach. So, I think the bottom line is that age is no longer as strong of a determinant to consider transplantation. You could consider it for patients, I would say, at least up to 75 years of age and maybe sometimes older if patients are in good shape. For patients who are not in good shape at any age, really it probably doesn’t matter. If the patient is not in good shape, it’s probably not a good idea. And as I pointed out, the flip side here is that if you have a very good response with combination therapy, you may not choose to do it as the default, and I think that’s the direction the field is going overall. So, I think the answer is both yes and no. If the patient wants to do it, you could certainly go forward and do it.

Transcript edited for clarity.

• A 74-year-old woman presented with anemia, proteinuria, renal insufficiency, and pain in her right hip
• History: chronic HTN, aortic insufficiency, diabetes mellitus
• ECOG performance status, 1
• X-Ray of the pelvis showed numerous lytic lesions in the ilium and a large lesion in the right proximal femur
• MRI confirmed a 9-mm lesion in the right femoral head and numerous bilateral T1 hypointense and T2 hyperintense lesions in both iliac region
• Laboratory results:
  • Hb, 10.1 g/dL
  • Ca²⁺3.32 mmol/L
  • Creatinine, 1.9 mg/dL
  • Creatinine clearance, 30 mL/min
  • M-protein, 1.4 g/dL
  • B2M, 4.9 mcg/mL
  • SFLC, kappa, 150 mg/dL
• Bone marrow biopsy, 70% plasma cells
• Molecular testing, del17p