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Something new: Pat’s journal article review

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Something new: Pat’s journal article review

I stumbled upon a fascinating journal article while I was doing some research for the post I ran about John yesterday.  Although I had seen the acronym, VDR-PACE, I wasn’t familiar with the PACE part (continuous infusions of cis-platin, doxorubicin, cyclophosphamide, etoposide) of John’s VDR-PACE inpatient induction regimen.

It seems that VDR (Velcade, dexamethasone and Revlimid (Also often written as VRD or RVD–can’t these doctors make up their minds?) has become so successful that you rarely hear about PACE anymore outside of Arkansas and UAMS.

The thing that struck me about this older journal of the American Society of Hematology article–known as blood–was the writing style.  It was surprisingly conversational in the way that it systematically laid-out the construct for three of the best known international myeloma experts today, Dr. Keith Stewart, Dr. Paul Richardson and Dr. Jesus San-Miguel.  The logic and science holds-up, despite the fact that the article is almost three years old.  And don’t let the title fool you.  There is plenty of information here for older myeloma patients, too!

As you might guess, it is a voluminous piece of work, so I can’t reproduce it all for you here.  But I’ve included a few important excerpts to help make it easy on you, and to illustrate my point:

How I treat multiple myeloma in younger patients

  1. A. Keith Stewart1
  2. Paul G. Richardson2
  3. Jesus F. San-Miguel3

Published online before print October 27, 2009, doi: 10.1182/blood-2009-07-204651 Blood December 24, 2009 vol. 114 no. 27 5436-5443

Our approach to treatment in younger “transplantation eligible” patients today is to use combination induction therapies that offer a high percentage likelihood of rapid and deep response. Although still controversial, we thus concur with the belief that maximizing initial response will for the majority of patients translate into better long-term disease control and survival. Treatment should therefore, in our opinion, use all available drugs of known effectiveness during initial therapy with careful attention to management of toxicities in a manner that ensures planned delivery of the intended therapeutics. In other words, we do not favor therapeutic rationing (ie, saving drugs for later)…

In patients with comorbidities who are ineligible for, or unwilling to, pursue multidrug combination therapies and/or high-dose therapy, a reasonable alternate goal of treatment is to seek the best continuous disease control with less emphasis on depth of response and more emphasis on obtaining adequate symptom relief while maintaining quality of life. In this situation, therapeutic layering (adding new drugs in patients not responding to initial therapy) may be more logical. We further think that treatment should be individualized both in respect to prognostic risk profile9 and adapted to meet the competing demands of comorbidities and age…

OK, so this isn’t light bedtime reading.  But the thing I like about it is the doctors then go back and support their approach in understandable detail.  Check-out this section:

Durable complete response is a desirable endpoint

There is a growing body of evidence showing an association between depth of response to therapy and improved long-term outcomes, including progressive-free survival (PFS) and overall survival (OS), in MM patients.3,5,8,2327 Using conventional chemotherapy, it has been shown that there is a correlation between response before and after transplantation and that the quality of response after transplantation has a marked impact on outcome.8,27 Importantly, however, studies suggest that if a patient achieves a complete response (CR), this must be durable and that the duration of CR (rather than obtaining CR per se) is the best predictor of OS.28 Furthermore, although obtaining a durable CR is of apparent statistical value for the majority of MM patients, there are some subgroups (usually identifiable only after initial therapy has been completed) in which the value of initially obtaining a CR in predicting long-term outcome is more questionable. These subgroups include the high-risk group of rapidly responding, but early relapsing patients (typically defined by poor risk genetics), those more indolent myelomas that revert to an “monoclonal gammopathy of uncertain significance like” profile after therapy and those myeloma patients (increasingly uncommon) with stable nonprogressive disease after induction therapy. At present, our ability to accurately predict who these persons are a priori and before treatment is initiated remains limited. Pragmatically then, one must still start with maximal response, including a high expectancy of CR, as a goal.

Trial data and our recommendations in the next section use current definitions of CR, but an important caveat for consideration is that these definitions are suboptimal because a CR is currently based on the relatively insensitive criteria of the disappearance of the M-protein by immunofixation, the presence of less than 5% plasma cells in the BM and complete disappearance of any extra-osseous plasmacytoma.29 Even with the incorporation of new criteria such as the absence of clonal plasma cells by immunohistochemistry to define stringent complete remission, experience suggests that these tests may still have low relative sensitivity. To further improve the assessment of treatment efficacy, more sensitive tools are required going forward and will be explored in clinical trials both at the BM level (such as multiparametric flow cytometry26) and outside of the BM (eg, imaging techniques, such as MRI or PET-CT30). In addition, when assessing CR, MRI defined lesions may take as many as 18 to 24 months to normalize.

This was very prophetic.   The move toward more stringent diagnostics has gained momentum at large myeloma treatment centers.  Another reason to seek a second opinion at a large cancer center that specializes in multiple myeloma?

The doctors go on to discuss initial therapy, how long to treat before transplant (induction), the role of transplantation, prognosis and genetics, therapy for non-transplant eligible patients and even supportive care.

How I treat multiple myeloma in younger patients is the perfect journal article for readers that are ready to move beyond the 20 page pamphlets distributed by the drug companies and IMF.  (If you don’t know what IMF stands for, you may not be ready for this beast!)

And I got a lot out of it, too.  Very comprehensive and–considering the genre–easy to follow.

CLICK HERE to read more.

Feel good and keep smiling!  Pat