[Cheryl G]

IMWG guidelines related to kidney damage

by Cheryl G on Fri Mar 18, 2016 2:29 pm

Revised International Myeloma Working Group (IMWG) guidelines were published earlier this week related to the diagnosis and management of kidney damage in multiple myeloma patients.

The abstract for the article describing the guidelines gives a summary of the main points of the guidelines. Below, I've broken up the abstract into its main points, grouped the points by subject, substituted brand names for the generic names of drugs and used the phrase "kidney damage" instead of "renal impairment" (RI).

The "grades" with each point ("grade A", "grade B", etc.) are meant to indicate the quality of the evidence in support of that particular guideline. A higher grade (such as an "A") indicates the guideline is based on more extensive evidence.

Here are the guidelines summarized in the abstract:

Importance of Testing for Kidney Damage

• All patients with myeloma at diagnosis and at disease assessment should have serum creatinine, estimated glomerular filtration rate, and electrolytes measurements as well as free light chain, if available, and urine electrophoresis of a sample from a 24-hour urine collection (grade A).

Methods for Checking Kidney Function

• The Chronic Kidney Disease Epidemiology Collaboration, preferably, or the Modification of Diet in Renal Disease formula should be used for the evaluation of estimated glomerular filtration rate in patients with stabilized serum creatinine (grade A).
• International Myeloma Working Group criteria for renal reversibility should be used (grade B)

Non-Myeloma Therapy Approaches to Protecting / Improving Kidney Function

• For the management of kidney damage in patients with multiple myeloma, high fluid intake is recommended along with antimyeloma therapy (grade B).
• The use of high-cutoff hemodialysis membranes in combination with antimyeloma therapy can be considered (grade B).

Treatment Recommendations For Patients with Kidney Damage

• Velcade-based regimens remain the cornerstone of the management of myeloma-related kidney damage (grade A).
• High-dose dexamethasone should be administered at least for the first month of therapy (grade B).
• Thalidomide is effective in patients with myeloma with kidney damage, and no dose modifications are needed (grade B).
• Revlimid is effective and safe, mainly in patients with mild to moderate kidney damage (grade B); for patients with severe kidney damage or on dialysis, Revlimid should be given with close monitoring for hematologic toxicity (grade B) with dose reduction as needed.
• Autologous stem cell transplantation (with melphalan 100 mg/m2 to 140 mg/m2) is feasible in patients with RI (grade C).
• Kyprolis can be safely administered to patients with creatinine clearance > 15 mL/min, whereas Ninlaro in combination with Revlimid and dexamethasone can be safely administered to patients with creatinine clearance > 30 mL/min (grade A).

Since this posting already is rather long, I will wait until later to share some of my thoughts on the recommendations.

Here's a link to the article for those of you who might have access to the full text:

MA Dimopoulos et al, "International Myeloma Working Group Recommendations for the Diagnosis and Management of Myeloma-Related Renal Impairment," Journal of Clinical Oncology, March 2016 (abstract)

[TerryH]

Re: IMWG guidelines related to kidney damage

by TerryH on Sat Mar 19, 2016 11:30 am

Thanks, Cheryl, for sharing this with the rest of us.

A couple of things caught my attention as being different than I would have expected.

I would not have expected the statements about Revlimid to be as "innocent" as they are. However, I think this is mainly a fault on my part. I thought there was evidence that Revlimid can damage the kidneys, but I seem to be wrong. I can't find any mention of this.

Instead, the main thing to worry about with Revlimid is that it's the kidneys that remove the drug from the body. So, when you give Revlimid to myeloma patients with kidney damage, you have to make sure to adjust the drug's dose. Otherwise, it will be like giving the patient an extra-high dose of the drug, which can lead to the negative side effects related to high Revlimid doses.

The other surprise, for me, is that the guidelines are as favorable to Kyprolis as they are. My recollection is that, while some researchers claim that Kyprolis is safe in patients with kidney damage, the evidence isn't particularly convincing (to put it politely).

[Multibilly]

Re: IMWG guidelines related to kidney damage

by Multibilly on Sat Mar 19, 2016 12:12 pm

Thanks for posting this Cheryl. I had found this article to be insightful when it comes to understanding how a couple of top multiple myeloma specialists view the challenge of treating multiple myeloma patients with RI. If you aren't registered on the site, it's free to do so.

http://www.medscape.org/viewarticle/746908_transcript

[Cheryl G]

Re: IMWG guidelines related to kidney damage

by Cheryl G on Mon Mar 21, 2016 6:38 pm

Thanks for your comments, Terry and Multibilly.

I had some of the same reactions you had, Terry. I think the key takeaway is that, for now, Velcade remains the novel therapy of choice for newly diagnosed patients with kidney damage.

Given some of the recent discussion here in the forum about a patient's treatment with high-dose dexamethasone, I also noticed the part of the guideline that mentioned that therapy.