The single most important question is: Is the treatment working as expected?

Appropriate expectations are as follows:

• The treating physician will have explained the benefits and side effects of treatment including the normal timeline such as when will symptoms improve, blood counts get better and myeloma protein levels drop.  If not, ask, because mutual understanding of what is expected is the key information required.
  
  
• Many times there will be some immediate or almost immediate benefit when treatment is started.  For example, steroids such as dexamethasone and prednisone immediately reduce inflammation and have an anti-myeloma effect, which can reduce pain and swelling and start to reduce the myeloma tumour burden right away.
  
  
• In general, additional treatment benefit occurs over a period of weeks to a few months (2-3 months).
  
  
• With the use of new novel agents, such as thalidomide, Revlimid, and Velcade, especially as part of 2-4 drug combinations (or greater) major response (>50-70% reduction) with reduction in myeloma levels, occurs within 6-8 weeks.
  
  
• Thus, careful monitoring after the first cycle of treatment (3-4 weeks) and/or second cycle of treatment (6-8 weeks) gives an excellent indication of if the treatment is working or not.
  
  
• Also, in general, it is agreed that 4-6 cycles of a particular therapy represents both an adequate trial and is sufficient to achieve initial response and disease control.
  
  
• Further therapy can be considered if there is an adequate level of ongoing but slower response and side effects are manageable/tolerable.
  
  
• However, 4 cycles is a typical preparation if there is intent to move ahead with stem cell harvesting and autologous stem cell transplant.  Often the transplant will be recommended and conducted even if the response level has been less than hoped for (for example, <50% reduction in myeloma levels).
  
  
• If transplant is not planned, then continued therapy of some sort for a total of 12-18 months is typically considered.  This would represent what is called consolidation and/or maintenance as discussed in STEP 7.
  
  
• If there is <50% reduction in the myeloma protein levels, careful review and discussion with the treating physician is required.  Options include:
  • Stop at that point: watch and wait if clinical improvement has occurred.
  • Switch to an enhanced or different combination to achieve better response.
  • Maintenance at reduced doses in an effort to achieve additional response over time.
    
    
• A crucial question is dependent upon the philosophy of the physician.  Is it essential to push to achieve a certain level of response, such as complete remission (myeloma protein gone: reduced by 100%) or is some lesser response ok?
  
  
• Accurate response assessment is crucial and the IMWG criteria can be used to document the exact status of the patient.
  
  
• A major focus of attention in recent years has been to evaluate the potential benefit of higher levels of response.  For example, as already noted, is it crucial to achieve CR?  How much worse is VGPR (if at all)?  Is VGPR better than PR?

REFERENCES

©2011 International Myeloma Foundation