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Total Therapy Demystified (Part One)

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Total Therapy Demystified (Part One)

For someone that isn’t a doctor, I know a lot about myeloma therapies.  Not so much about the science of how they work, but the timing of it all–when best to use them and ways to help minimize side effects.  But I still have a lot to learn about one specific treatment philosophy: Total Therapy.

I shared a quick overview of Total Therapy on Saturday:

Total Therapy (TT) was developed in Arkansas at the Myeloma Institute, a part of the University of Arkansas Medical Center (UAMS).  In a nutshell, docs there use tandem stem cell transplants, sandwiched between just about every combination of current myeloma therapy there is.  Treatment is relentless and intense–and can last four or five years.  But their OS numbers are impressive, especially for low risk patients.

I’m no expert on Total Therapy, so I have invited someone that is–UAMS myeloma patient and blogger, Nick Van Dyk–to help educate us about how Total Therapy works, how it originated and what it’s like being a UAMS patient.  I will run Nick’s contribution tomorrow.

Well, tomorrow is today!  So here is Nick’s detailed, well-thought-out take on Total Therapy:

Total Therapy Demystified

Multiple myeloma survivor and Total Therapy Patient Nick Van Dyk

NIck VDI’ll do my best to keep this fact-based and totally objective.  And a further disclaimer: I am a patient, not a doctor.  This comes from the perspective of a reasonably educated layman and should not be construed in any way as medical advice from a qualified professional.

Total Therapy refers to a series of protocols designed to cure Myeloma.  It is based on work done at St. Jude’s hospital on childhood leukemia, where over a series of 40 years the “cure fraction” of children with newly diagnosed ALL (acute lymphoblastic leukemia) rose from under 10% to over 90%.  The hypothesis behind the work done at St. Jude’s was that ALL could be cured if, instead of using a sequence of agents until each failed, patients received a broad variety of agents in rapid succession including induction, consolidation and maintenance.  The disease attempts to resist an attack from one pathway, only to be attacked by another pathway, and so on — the clones have nowhere to turn and they cannot develop drug resistance quickly enough to escape the therapy.

Total Therapy for Myeloma was developed at MD Anderson in Houston and then taken to the University of Arkansas for Medical Sciences in Little Rock where it has continued to evolve over the past 20+ years.  The hypothesis behind TT is that ALL, like multiple myeloma (MM), begins with B Cells that mutate, and that the demonstrated curability of ALL could be replicated in MM.

TT has gone through several different protocols.  Current protocols include the TT4 protocol (which is used for newly diagnosed low-risk patients, who represent 85% of the newly diagnosed patient pool), the TT5 protocol (used for newly-diagnosed high-risk patients) and I believe the TT6 protocol, which is used for previously-treated patients.  The one which is most often referenced is TT4, because it is with this group that UAMS claims a very high cure rate — about 60% of newly diagnosed patients achieve complete remission and 90% of these are believed to be cured by UAMS.  Additionally, many of the patients that do not achieve complete remission do achieve a minimum residual level of the disease, similar to MGUS, which most times does not progress.  All of this per UAMS data, which one can choose to believe or not to believe as one sees fit.

EDITOR’S NOTE:  For the uninitiated, Nick’s last statement might seem to come out of left field.  Let me explain.  Total Therapy’s numbers have been attacked regularly by some outside clinicians and researchers.  Why?  Good question!  My understanding is that UAMS keeps a lot of its data in-house and doesn’t always share it freely with outside evaluators.  One accusation is that UAMS’ TT numbers are “fudged” and not as strong as UAMS reports.  Another is that they under report the number and severity of side effects associated with TT.  Standard research protocol requires research be duplicated successfully by others.  Since few cancer centers follow strict TT guidelines–and certainly don’t treat as many patients as they do in Arkansas–UAMS results are sometimes called into question.  TT supporters argue it is jealousy or a lack of understanding and/or commitment to the program that leads others to question or disrespect TT’s numbers.  All I know is this:  It would be a shame if myeloma patients were denied access to a powerful therapy option for non-scientific reasons.

As high risk patients have a difficult prognosis everywhere, and as previously-treated patients are very unlikely to have a chance at being cured through Total Therapy (because of drug-resistance caused by incremental drug exposure), the protocol of most interest is TT4.

TT4 follows directly from the TT3 protocol that began around 2003.  The TT3 protocol was the first of the TT protocols to include so-called “novel agents” — in this case Velcade and Revlimid.  At the time, very few major cancer centers were using either of these drugs in newly diagnosed patients, choosing to hold them in reserve for relapse.  TT3, per UAMS, achieved high cure fractions that they believe could not be improved upon.  The intent of TT4 was to see if dosage could be reduced without reducing the cure fraction.  So TT4 tests a “standard arm” against a “lite arm” and measures outcomes.  At this point, per UAMS, the two are interchangable, which will likely lead to TT using less of the highly toxic agents that it employs.

Your regular readers will likely know that treatment of Myeloma usually begins with Induction, followed by a Transplant in some cases, then sometimes followed by Maintenance.  Total Therapy approaches all of these slightly differently than more conservative treatment approaches and includes a Consolidation phase before Maintenance as well.  The agents used in these phases of treatment are described below.

Let’s pause here and continue with specifics about Total Therapy tomorrow.

Feel good and keep smiling!  Pat