Renal rescue for

myeloma patients

Introducing Myeloma Kidney Therapy

A new lifeline for myeloma
kidney patients
Even as they fight their cancer, multiple myeloma patients can be
forced to face an unwelcome effect of their condition—the serious
risk of acute and chronic renal failure. A new therapy under eval-
uation can help them combat renal impairment and perhaps add
a few more—and better—years of life with their families.

Fighting cancer—and renal failure

Multiple myeloma is a serious and chronic illness. But often renal failure—
as a further consequence of their disease—drastically worsens the patient’s
condition and shortens the time they have left. Renal failure is caused by an
unwelcome by-product of myeloma—unmanageable quantities of Free
Light Chain (FLC) proteins.

A new option for Free Light Chain removal

Until now, there has been little success in attempts to use blood purification
techniques to remove these damaging molecules, and stop them disrupting
the kidneys. But the new Myeloma Kidney Therapy made possible by Gambro
could be a lifeline for many of these patients.

More time for patients and their families?

Initial pilot studies of the new therapy, as well as predictions derived from
modeled survival data, point to long-term clinical benefits and a cost-effective
use of healthcare resources in comparison with historical controls.1,2,3,7 The
difference for patients and their families can be measured in months and even
years. These findings are currently being validated in an on-going randomized
controlled trial.
 Multiple myeloma and the kidney
Myeloma causes the overproduction of proteins that impair
renal function and subject the patient to additional complica-
tions. Unfortunately current treatments have shown no clinical
benefit in the prevention of renal damage.1

FLCs and cast nephropathy

Because of the overgrowth in their plasma cells, many myeloma patients
have abnormal levels of FLCs in their blood.
When these excessive amounts of FLCs reach the kidneys and pass
through the glomerular fenestrations, they overwhelm the absorptive
capacity of the proximal tubules.
Unchecked, they enter the distal tubules and co-precipitate with
Tamm-Horsfall proteins to form waxy casts (cast nephropathy) that both
block the flow of urine and cause interstitial inflammation.

Immunoglobulin

Glomerulus
Immunoglobulin Distal tub

Glomerulus
Distal tubule

FLCs

Proximal tubule:
Plasma cell FLCs Excessive FLCs
FLCs cannot be processed

Proximal tubule:
cell FLCs Excessive FLCs
cannot be processed
The unwelcome risk of renal failure
Approximately 10–20% of multiple myeloma patients experience dialysis-
dependent acute renal failure.4,5 Of these patients, studies show that—at
best—little more than a third recover renal function through standard HD,
with most of the studies reporting significantly less success.

Current treatments are not the answer

At present, myeloma kidney patients are treated through attempts to
remove FLCs:

• Plasma exchange is a logical approach, but shows no clinical benefit.6

A 3.5 L plasma exchange removes 65% of intravascular FLCs but has
very little impact on overall FLC levels—because they are also present
in similar concentrations in the extravascular compartment and tissue
edema fluid

• On the whole, dialyzers are similarly ineffective when used to remove

FLCs and do not clear sufficient quantities to offer any real benefit to
the patient1

FLCs + Tamm-Horsfall
proteins produce casts
(cast nephropathy)
A new choice:
Myeloma Kidney Therapy
A therapy for myeloma kidney patients is now available. Thanks
to the emergence of an innovative, new technology from Gambro.

A combination of effective chemotherapy,

FLC removal and monitoring
Initial studies show that the solution for these patients with acute renal
failure is Myeloma Kidney Therapy:

• Effective chemotherapy to reduce the number of malignant,

FLC-secreting plasma cells

• Efficient direct removal of FLCs from the serum

• Accurate and rapid monitoring of FLC levels to ensure optimized

treatment (see end of brochure for details on Freelite™ immuno­
diagnostic assays)

Theralite™ High Cut-off technology

It is with a new technology for the efficient and direct removal of FLCs
that Gambro has been able to provide the missing ingredient. Theralite™
High Cut-off technology is uniquely successful in removing FLCs because
its large pores do not restrict removal.1

Rapid reduction in serum FLC concentrations

Clinical studies report very positive results for Myeloma Kidney Therapy.2
Through the combination of direct removal using Theralite and effective
chemotherapy, FLC levels are rapidly reduced.

Theralite™ High Cut-off technology

is characterized by very large pores, three
times the size of a normal High Flux
membrane. During treatment with con-
ventional dialysis techniques, these pores
allow larger molecules such as proteins
(in the molecular weight range 15 to 45 kDa)
to pass through the membrane.
In combination: Myeloma Kidney Therapy

Theralite™
High Cut-off technology

chemotherapy

Freelite™

High Cut-off permeability

High Cut-off

High Flux
Low Flux

FLCs
Middle molecules such as ϐ2m
Small molecular weight uremic toxins e.g. urea, creatinin, phosphate
Cost-effective rescue—a health
economics evaluation
Recent pilot studies in the United Kingdom1,2 indicate that
Myeloma Kidney Therapy provides major benefits for patients
with acute renal failure associated with multiple myeloma in
comparison with historical controls—up to 70% may recover renal
function.2 Health economics analyses using a Markov simulation
model show that the therapy is cost-effective as well.7,8

Predicted outcomes with Myeloma Average life expectancy based on modeling

Kidney Therapy (in years)
1.8
1.6
• Greater probability of recovering renal function and greater long-
1.4
term survival 1.2
Health economics modeling predicts an average survival of 1
0.8
9.37 months for patients on standard HD. Using Theralite that
0.6
figure becomes 20.1 months. 0.4
0.2
0
• Permanent dialysis can be avoided or at least substantially delayed
Standard HD HD with Theralite
It is estimated that 90% of all multiple myeloma patients treated
with standard HD require permanent dialysis during their lifetime.
And 75% of patients may need permanent dialysis after their first
presentation of renal failure. With Theralite, the modeling shows
that only 64% of patients may require permanent dialysis and over
50% of these will not need it until after they experience a multiple
myeloma relapse.

Putting budgets to the very best use

Myeloma Kidney Therapy, with Theralite™ High Cut-off technology at
its heart, delivers a favorable cost-effectiveness ratio, well within the
commonly considered range.3 Quite simply, it’s using resources in the
right way, and for the right reasons: to significantly prolong a patient’s
life with their families and improve the quality of those years.

The next step?

A randomized controlled trial is on-going to confirm these positive
results. But from what we know today, the sooner suitable patients
can start Myeloma Kidney Therapy, the better. Contact us today to
find out more.
Further reading
Projected survival data7,8
Comparing treatment through Theralite™ High Cut-off technology with conventional HD,
simulation analysis demonstrates that fewer patients are expected to need permanent dialysis
(64% vs. 90%). Patients are forecast to gain 0.9 additional years of life (1.7 vs. 0.8) and 0.6 additional
QALYs (1.1 vs. 0.5). The table below illustrates the percentage of patients alive at each stage,
clearly showing the potential improved survival rate as the two patient groups progress—or not.

Presentation 1st relapse 2nd relapse 3rd relapse

100% 52.5% 23.9% 10.9%

Theralite

100% 18.8% 6.2% 2%

Standard HD

References
1. Hutchison CA, Cockwell P, Reid S, Chandler K, Mead GP,
Harrison J, Hattersley J, Evans ND, Chappell MJ, Cook M,
Goehl H, Storr M, Bradwell AR. Efficient removal of immuno­
globulin free light chains by hemodialysis for multiple myeloma:
in vitro and in vivo studies. J Am Soc Nephrol. 2007
Mar;18(3):886-95
2. Hutchison CA, Basnayake K Cook M, Bradwell AR, Cockwell P.
Free Light Chain Hemodialysis Increases Renal Recovery Rate
and Improves Patient Survival in Patients with Cast Nephropathy.
Nephrol Dial Transplant Jun; 1 (Suppl 2): ii9a, 2008
3. Devlin N, Parkin D. Does NICE have a cost-effectiveness
threshold and what other factors influence its decisions?
A binary choice analysis. Health Econ. 2004 May;13(5):437-52
5. Knudsen LM, Hjorth M, Hippe E. Renal failure in multiple
myeloma: reversibility and impact on the prognosis. Nordic
Myeloma Study Group. Eur J Haematol. 2000 Sep;65(3):175-81
6. Clark WF, Stewart AK, Rock GA, Sternbach M, Sutton DM,
Barrett BJ, Heidenheim AP, Garg AX, Churchill DN; Canadian
Apheresis Group. Plasma exchange when myeloma presents
as acute renal failure: a randomized, controlled trial. Ann
Intern Med. 2005 Dec 6;143(11):777-84
7. Grima D. Modeled Long-term Clinical Outcomes and Cost-
effectiveness of Hemodialysis with the Gambro HCO 1100 Dialyzer
Versus Standard Hemodialysis in Patients with Renal Failure
Secondary to Multiple Myeloma. 2008. Available on request from
Cornerstone Research Group Inc.

4. Bladé J, Fernández-Llama P, Bosch F, Montolíu J, Lens XM,
Montoto S, Cases A, Darnell A, Rozman C, Montserrat E.
Renal failure in multiple myeloma: presenting features and
predictors of outcome in 94 patients from a single institution.
Arch Intern Med. 1998 Sep 28;158(17):1889-93
8. Sonnenberg FA, Beck JR. “Markov models in medical decision
making: a practical guide.” Medical Decision Making, Vol.13,
No. 4:322-38 1993
Ordering information
Please contact us to order Theralite™ High Cut-off technology
or receive more information:
partner@gambro.com

About Freelite
Freelite assays were developed by The Binding Site to measure free
lambda and free kappa immunoglobulin light chains. Freelite is an
award-winning breakthrough for the detection and monitoring of
Multiple Myeloma and other B-cell dyscrasia.

For more details about Freelite immunodiagnostic assays

including ordering information, please contact:
www.bindingsite.com
 Sweden
PO Box 10101
SE-22010 Lund

www.gambro.com
Gambro Lundia AB

partner@gambro.com
Phone + 46 46 16 90 00
Gambro® is a registered trademark of Gambro Lundia AB. Theralite™ High Cut-off technology is a trademark of Gambro Lundia AB filed for registration in the European Community HCEN5379_1 ©2008.09. Gambro Lundia AB