Transcript Yes - Imedex

Should We Treat Smoldering Myeloma?
YES!
Lymphoma Myeloma 2014
Scottsdale, Arizona
Rochester, Minnesota
Jacksonville, Florida
Joseph Mikhael, MD, MEd, FRCPC, FACP
Staff Hematologist, Mayo Clinic Arizona
Additional Disclosures
• There is no such thing as Mikhael
Oncology
James R. Berenson, MD
• I am not incorporated
• I am just the average Joe…
President and CEO - James R. Berenson, MD, Inc.
Medical & Scientific Director - Institute for Myeloma
& Bone Cancer Research (IMBCR)
Chief Executive Officer - Oncotherapeutics
Background
• Remember Myeloma is a unique cancer –
defined by the presence of organ damage –
not just pathology
• Traditionally we wait until CRAB
• But does that really make sense? Do we
have to wait until damage is present to
intervene??
What if your friend is walking towards a cliff?
• Will you wait until they are falling to rescue
them?
• What if they are running?
•
What if they are enjoying the
walk?
My Thesis – there are 3 groups within
Smoldering Myeloma
• Group 1: “Ultra” High Risk
• Plasmacytosis ≥ 60%
• Involved/Uninvolved Light Chains ≥ 100
• 1 or more focal lesions on MRI/PET
TREAT AS IF TRUE MYELOMA
• Groups 2: High Risk (Defn to follow)
DEBATE: To Treat or Not to Treat
• Group 3: Low Risk
DON’T TREAT
Smoldering Multiple Myeloma
Ultra-High Risk
•
>60% BMPC
•
FLCr >100
•
>1 MRI focal
lesions
High-Risk SMM
25%/year
Low-risk SMM
5%/year
SMM Paradigm Shift
SMM
10% per year x 5 years
MGUS
~1% per year after 10 years
Ultra High Risk SMM = Active
Myeloma
Not CRAB but now SLiM CRAB
• S (60%)
• Li (Light chains I/U >100)
• M (MRI 1 or more focal lesion)
• C (calcium elevation)
• R (renal insufficiency)
• A (anemia)
• B (bone disease)
Bone Marrow Plasma Cell ≥60%
Rajkumar SV et al. N Engl J Med 2011; N Engl J Med 2011; 365:474-475
FLC Ratio >100 and Risk of progression to myeloma
>100
<100
Larsen J, et al. Leukemia advance online publication 27 November 2012; doi: 10.1038/leu.2012.296
Rajkumar SV, Merlini G, San Miguel JF. Nat Rev Clin Oncol 2012
High Risk SMM = Median TTP ~2 years:
• Mayo: SMM with M protein ≥3 gm/dL and ≥10% PCs
• Spanish: ≥10% PCs, Absence (<5%) of normal PCs by
immunophenotyping and Immunoparesis of ≥1
immunoglobulins
•
•
•
•
•
•
•
Abnormal FLC ratio 8-100
Deletion 17p, t4;14, 1q amp
Evolving pattern
IgA SMM
SMM with M protein ≥4 gm/dL
Increased circulating plasma cells
Increased plasma cell proliferative rate
Rajkumar SV, Merlini G, San Miguel JF. Nat Rev Clin Oncol 2012
Management of High Risk
SMM:
What does the data say?
Do we believe the Spanish
Trial?
Recall – Randomized, Phase 3
Trial of high risk SMM pts
Lenalidomide –
dexamethasone vs observation
Len/Dex versus Observation in High Risk SMM: TTP
Mateos M et al. N Engl J Med 2013;369:438-447.
Len/Dex versus Observation in High Risk SMM: OS
Mateos M et al. N Engl J Med 2013;369:438447.
Issues with the Spanish Trial
1. Generalizability
– Mayo Criteria - BMPC ≥ 10% and M-protein ≥ 30 g/L
or
– Spanish Criteria BMPC ≥ 10% or M-protein ≥ 30 g/L and
– BM aPC/nPC > 95% and
– immunoparesis
– BUT note that 60% met Mayo Criteria!!
2. Tolerability
Mateos M et al. N Engl J Med 2013;369:438-447.
3. Consequences
Len-dex vs. no treatment: TTP to active disease (n = 119)
ITT analysis
Median follow-up: 32 months (range 12–49)
Lenalidomide + dex
Median TTP: NR
1.0
Proportion of patients alive
9 Progressions (15%)
5 pts:early disc followed by PD
0.8
4 pts:symptomatic PD
0.6
No treatment
0.4
Median TTP: 23m
0.2
37 Progressions (59%)
20 patients: bone disease
HR: 6.0; 95% IC (2.9–12.6); p < 0.0001
7 patients: renal failure
0.0
0
5
10
Mateos. ASH 2012
15
20
25
30
Time from inclusion
35
40
45
50
Spanish Trial Conclusions
• Early intervention in high risk SMM
• Prolongs TTP
• Improves OS
• Does not result in appreciable toxicity
• Prevents irreversible damage to kidneys
and bones that occur …
“on our watch!”
Conclusions
• Don’t forget new criteria (SLiM CRAB) for
myeloma (Ultra High Risk SMM = Myeloma)
• Low risk can be watched
• High risk is complex
• Recall 50/50 in 2 years
• Consider therapy these patients in an
individualized manner
• Not limited to len-dex, but all active
therapy
Don’t let your patients fall…