Ist International Myeloma Working Group (IMWG)
Myeloma Training Course: Master Class
Day by Day Summary of Key Points
August 8, 2012
Dr. Robert Vescio
STEP 4: Supportive Care: And How To Get It
- The underlying biology of myeloma bone disease was presented
- Dr. Vescio discussed the anti-osteoclast and potential anti-myeloma effects of bisphosphonates such as AREDIAÂ®, ZOMETAÂ® and ClodronateÂ®
- The Risk Factors for, and management of, ONJ were discussed. The current frequency of occurrence is approximately 3-5 % having been 5-10% only 5-10 years ago when there was much less awareness RE: Prevention and management strategies. A key aspect of prevention is to avoid tooth extraction for patients receiving bisphosphonate therapy. Expert dental consultation may be required to assess alternate management options. It appears that ONJ is rare in China (or rarely observed).
- The benefits of vertebroplasty and kyphoplasty were discussed
- A Range of other supportive care measures were discussed including:
- Hypercalcemia management
- Renal insufficiency or failure
- Spinal cord compression
- Infection complications
- As the Director of the Amyloid Center @ Cedars-Sinai Comprehensive Cancer Center, Dr. Vescio also discussed the biology, types , clinical features and management of amyloidosis both systemic and localized.
- Cardiac amyloidosis was identified as the key high risk feature
- It was emphasized to avoid simple oral MP (melphalan/prednisone) in treatment of amyloidosis
- Conversely the value of VELCADE, REVLIMID and ASCT in selected patients was reviewed.
- Review was provided by Dr. Yanchen Li from Chaoyang Hospital in Beijing
August 14, 2012
STEP 5: Transplant: Do You Need One?
- The Role of Transplant in 2012 was presented and discussed by Dr. Bill Bensinger
- Options for Frontline induction pre-ASCT were again discussed. Regimens identified were:
- VCD (Velcade/Cytoxan/Dex)
- PAD (Velcade/Adriamycin/Dex)
- VTD (VRD if available) (Velcade/Thalidomide or Revlimid/Dex)
- Rd (Revlimid/low dose Dex)
- The time of transplant was reviewed at length considering "early" versus "late" discussing the various PFS and OS outcomes
- In general 4 cycles of induction were recommended before transplant, with a plan for transplant irrespective of Response in the absence of progressive disease. It was not recommended to continue or change induction with a view to achieving better response prior to proceeding to transplant.
- It was emphasized that it is important to focus on quality of life (QOL) in considering alternative treatment strategies.
- The standard preparative regimen for autotransplant is Melphalan 200 mg/m2.
- A second transplant should rarely be considered as a planned tandem transplant. However, a second transplant can be considered if:
- There is < VGPR with a first transplant and there was significant evidence of cytoreduction (response) with the first transplant.
- If there is a > 2 year remission with a first transplant, especially if unmaintained
- At relapse if there are limited alternative options
- Earlier in the disease course if limited options exist
- There was an extended discussion re: the pros and cons of post-transplant maintenance primarily in reference to the REVLIMID data in the IFM and CALBG trials. The doubling of PFS was noted as was the improved OS in the CALGB trial. Also noted was the increased occurrence of second primary malignancies (SPMs) - overall at about a 5-7% level in these settings.
- Distinction was made between the rare 20 AML which is unfortunately usually rapidly fatal and the more common second solid malignancies which are typically well managed or curable and do not impact overall survival. Overall, the net benefit is therefore in favor of maintenance for a majority of patients.
- In China, Thalidomide is available and is used for maintenance. VELCADE is also available, but too expensive for use in China. Revlimid is not yet available.
- Potential novel transplant preparative regimens were discussed:
- "VEL/MEL": VELCADE given prior to high-dose melphalan
- Melphalan @ 280 mg/m2 using Amifostine as a protective agent
- Protocols for stem cell mobilization were discussed including: G-CSF, G-CSF + Cytoxan and G-CSF + Prelixafor (MOZOBILTM) Mozobil is not available in China. Risk factors for "Mobilization Failure" were discussed.
- Pre-transplant, it is important to identify and exclude patients with pre-existing MDS (can use Cytogenetics/FISH/FLOW analyses). Second harvesting can be carried out later in the disease course if necessary.
- The very poor outcome with full allotransplant was noted. Although, rarely performed in the U.S.: it is still an option in China.
- Overall guidelines for transplant were summarized:
- Autotransplant: Still a standard of care if feasible
- Allo transplant: Rarely indicated
- Mini-Allotransplant Recommended for use in clinical trials for "High Risk" patients
August 9, 2012
Dr. Vincent Rajkumar
STEP 6: Response Assessment: Is Treatment Working?
- Dr. Rajkumar first reviewed the basics of Response Criteria as outlined in the Uniform Response IMWG Manuscript of 2006.
- Potential pitfalls were emphasized including
- Relapse from CR or a very low level of M-component which requires both at >25% increase AND > 500 mg/dl increase on SPEP.
- At higher levels of response the M-component increase be at least > 1.0 GMS/dl if lowest level of serum M-component is 5 Gm/dl
- Dr. Rajkumar provided great caution about evaluating "responders" as a group, because many time dependent and other biases can account for improved outcomes
- In addition the fact that improved progression free survival (PFS) may not lead to improved overall survival (OS) was reviewed in detail with examples from numerous trials
- It was also emphasized that "High-Risk" and "Good Risk" patients must be identified and evaluated separately.
- Surrogate markers were discussed. An M-Component is a surrogate marker which is usually quite reliable, but ultimately is only as indirect indicator of myeloma disease status. There can, for example, be light chain or Bence Jones escape when the Serum M-component can be misleading.
- Cytogenetics and FISH, as well as, Gene Expression Profiling (GEP) are key prognostic factors which the Mayo Team has organized as part of the mSMART program available on the web.
- A simple recommendation for 2012 is:
- High-Risk: if feasible consider use of VRD (Velcade/Revlimid/Dex) induction
- Standard (including Low) Risk recommended
- VCD (Velcade/Cytoxan/Dex)
- Rd (Revlimid/low dose Dex)
As Key Choices
- In other situations consider:
- DT-PACE for plasma cell leukemia or extramedually disease
- VCD/VRD/VTD/PAD all to be considered for Relapsing Patients also
- The current diagnostic criteria for Amyloidosis were reviewed
- The current "Clinical Trials Program" at the Mayo Clinic was presented and felt to be an excellent and quite impressive impressive model for China.