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Velcade-Doxorubicin-Dexamethasone Treatment Can Reverse Kidney Damage Associated With Multiple Myeloma

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Published: Sep 24, 2010 11:25 am

The results of a recent Phase 2 trial indicate that Velcade-doxorubicin-dexamethasone treatment can reverse multiple myeloma-associated kidney damage in myeloma patients suffering from kidney failure. The regimen also improved patients’ disease statuses and was associated with few severe side effects.

Multiple myeloma affects plasma cells, a subset of white blood cells that fight infections by producing antibody. In multiple myeloma patients, cancerous plasma cells produce one kind of abnormal antibody.

In some myeloma patients, this abnormal antibody binds to a protein produced in the kidney.  These antibody-protein complexes then accumulate in the structures of the kidney, causing damage and decreased kidney function.

Kidney damage is a common and potentially serious complication in multiple myeloma. Reversal of this damage can only be achieved by preventing the accumulation of protein-antibody complexes in the kidney.

Previous studies have suggested that Velcade (bortezomib) and Velcade-based regimens are particularly effective in reversing kidney damage in multiple myeloma patients.

Additionally, the active compounds in Velcade are broken down in the body through processes that do not involve the kidneys. As a result, Velcade does not interfere with kidney function and usually does not cause kidney-related side effects.

In this clinical trial, researchers investigated the efficacy of Velcade-doxorubicin (Adriamycin)-dexamethasone (Decadron) (referred to as VDD) in myeloma patients with antibody-associated kidney damage and the treatment’s potential of restoring kidney function in this patient population.

Sixty-eight multiple myeloma patients with antibody-associated kidney damage were treated with VDD. During the study, patients received a median of eight treatment cycles.

A total of 66 percent of patients achieved a partial response or better, and 38 percent of patients achieved a complete response.

Sixty-two percent of patients showed improved kidney function with VDD treatment. Kidney function was restored in 31 percent of patients.

Nine patients enrolled in the study were receiving dialysis due to severe impairment of kidney function. Three of these nine patients became dialysis-independent following treatment.

Researchers noted that kidney improvement correlated with response to treatment. Patients who achieved a complete or very good partial response showed the greatest improvement in kidney function.

Median progression-free survival time was 12 months, and the median overall survival time had not yet been reached.

Low red blood cell count was the most common and severe side effect of the treatment and was experienced by 50 percent of patients in the study.

Infection was the most severe side effect not related to blood cell levels. Serious infections were experienced by 19 percent of patients and resulted in four patient deaths.

For more information, see the article in the Journal of Clinical Oncology (abstract).

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  • Chuck said:

    This is interesting news. Thanks for letting us know about it.

    I have a few questions, though, about the study.

    First, were the patients in the study newly diagnosed? If so, was this treatment given instead of any kind of a stem cell transplant, or was it sometimes given in addition to a stem cell transplant?

    Second, I thought it was interesting that kidney condition improved the most in patients who also responded the best to the treatment. Is this commonly the case? Do patients with kidney issues who respond to myeloma treatment often see there kidney problems go away? Or are the results seen in this study somewhat unique?

  • Beacon Staff said:

    Dear Chuck,

    Thanks for your excellent questions.

    Most patients were newly diagnosed (74 percent), but the remaining 26 percent had received one or more lines of previous therapy. The report does not mention the use of stem cell transplants or describe any treatment that the participants may have received after Velcade-doxorubicin-dexamethasone.

    It is common for patients who respond to myeloma therapy to show an improvement in kidney function, particularly those who are treated with novel agents. You may be interested in several other Beacon articles about the treatment of kidney-impaired patients with thalidomide-dexamethasone or Revlimid-dexamethasone. Additionally, you may be interested in a comparison of treatment with novel agents compared with conventional chemotherapy in patients with impaired kidney function.

  • Kansas said:

    It's no wonder patients have a hard time making decisions on the best treatment. My husband has had a very good response to Velcade/Dex = going from an M spike of 1.1 to .1 and a Kappa Light chain ratio of 6.98 to 1.24, and if I'm reading the recent BMB right - that has gone from 8% to 1%, however, still has a creatinine of 3.1 -- started at 4.8. Now docs want to do a stem cell transplant - discussion on Monday -- and I'm sure will want to use the chemo that passes through the kidneys. So do we go that route or continue with Velcade/Dex (has had 6 cycles). We'll see how the docs that make their living from stem cell transplants answer that question!!!

  • Chuck said:

    Thanks, Beacon Staff, for responding to my question. The additional information you provided is very helpful.

  • Justme said:

    Kansas: I just wanted to share with you my experience. When I was diagnosed with last stage MM and I was in kidney failure; Creantinine was 8.9. I was put on dialysis and Velcade. After two months on Velcade I was able to stop dialysis. My transplant was done with a lower dose of the drugs that are processed through the kidneys due to my previous kidney failure. I had "complete response to transplant" and have remained off dialysis, my Creantinine is now 1.6. My transplant was four years ago this month. Our situations are all so very different. Truly the best advice I think is to soak up as much info as you can and then make the decision that feels right for you. Blessings to you and your husband.

  • Kansas said:

    Thanks so much for sharing your experience -- we learn so much from each other -- and certainly share in the joys of successful treatment. Congratulations on successful transplant and being off dialysis for 4 years - wow!!! Options we were given were to harvest only; harvest/stem cell transplant; wait and see; maintenance -- all options are the right ones according to transplant center. He is considered to be in complete remission right now-we are thankful for that blessing!! Right now doing pre-transplant appointments and if ok given - harvest and then make next decision. Stay well my friend.

  • Son of survivor said:

    Hello. I frequent this web page and found this article very interesting. My father (60yo) was diagnosed with Stage 1/early stage 2 MM in 2006. They did a stem cell transplant and we couldnt be happier. He was being given revlimid at the time. He was in remission until Feb. 2010 when he experienced acute kidney failure. Creatinine reached an astounding 14.7! It also appeared that the MM was back. He was in the ICU since he was also being treated for a staph infection which was causing an abstruction in his airway. We were considering doing a kidney dialisis but the doctors determined that since this was an acute condition, and he would bounce back through close supervision, coupled with a very low sodium diet and lots of water. Sure enough, his creatinine steadly dropped at an average of 1 point every day. 2 weeks after he checked in, he was released. Creatinine is now at 1.3. We check it every time he goes in for chemo. Doctors said he was in remission last month after bi-weekly treatments of Decadron and Valcade. Hes currently doing once a week treatments and may switch to bi-monthly treatments.

    What I can pass to you is that, my father was never the healthiest person. Hes always been out of shape.He was able to beat it twice. Stay hydrated. keep those kidneys flushing. 2-2.5 liters of water daily. Maintain a decent diet and you'd be surprised how positively your body will respond. It did with my dad!

    I'll make it a point to chime in more from time to time on these stories. God bless you.

    -A survivor's son