LWBK1006-34 LWW-Govindan-Review November 24, 2011 11:25
470 DeVita, Hellman, and Rosenberg’s CANCER: Principles and Practice of Oncology ReviewAnswer 34.4. The answer is D.
The diagnostic criterion for plasma cell dyscrasias was recently revised.
Multiple myeloma is defined as a plasma cell dyscrasia associated with
end-organ dysfunction (acronym CRAB: hyperCalcemia, Renal failure,
Anemia, or Bone lesions). Patients should also have greater than or equal
to 10% clonal plasma cells and a monoclonal protein in serum and/or
urine. In the absence of organ involvement, the plasma cell dyscrasia
is classified as monoclonal gammopathy of undetermined significance
(MGUS) if the monoclonal protein levels are less than 3 g/dL and the
bone marrow contains less than 10% clonal plasma cells, and as smol-
dering myeloma if the bone marrow has greater than or equal to 10%
clonal plasma cells and/or monoclonal protein of greater than or equal
to 3 g/dL. On the basis of the above criteria, this patient has a smolder-
ing myeloma. Recently, the natural history of these indolent plasma cell
dyscrasias has been better defined. MGUS transforms to a clinically sig-
nificant plasma cell dyscrasia at a constant rate of approximately 1% per
year (Kyle et al. N Engl J Med. 2002;346[8]:564–569). The serum level
of the monoclonal protein and the type of monoclonal protein (IgA and
IgM>IgG) were risk factors for progression in the same study. In a subse-
quent study, Rajkumar et al. (Blood. 2005;106[3]:812–817) proposed a
risk stratification model that included three risk factors (abnormal SFLC
ratio, non-IgG-type monoclonal protein, and monoclonal protein con-
centration>1.5 g/dL) to further help predict progression of MGUS to
a clinically significant plasma cell dyscrasia. Kyle et al. (N Engl J Med.
2007;356[25]:2582–2590) reported that the overall risk of progression of
smoldering myeloma is approximately 10% per year in the first 5 years,
3% per year in the next 5 years, and decreases to 1% per year thereafter.
On the basis of this study, this patient has a 5-year risk of progression
of approximately 50%. Kyle et al. further classified smoldering myeloma
into three risk groups with different rates of progression: group (1) bone
marrow plasma cell greater than or equal to 10%, monoclonal M protein
greater than or equal to 3 g/dL: 15-year progression rate 87%; group (2)
bone marrow plasma cells greater than or equal to 10%, monoclonal M
protein less than or equal to 3 g/dL: 15-year progression rate 70%; and
group (3) bone marrow plasma cells greater than or equal to 10%, mon-
oclonal M protein greater than or equal to 3 g/dL: 15-year progression
rate 39%.Answer 34.5. The answer is D.
Decreasing the dose of bortezomib to 1 mg/m^2 is effective in decreas-
ing neuropathy as shown in the CREST trial and is recommended as
per the FDA guidelines. Decreasing the frequency of administration of
bortezomib has also been shown to decrease the rates of neuropathy
(Mateos et al. Lancet Oncol. 2010 Oct;11(10):934–941 and Palumbo
et al. J Clin Oncol. 2010 Dec 1;28(34):5101). However, both these stud-
ies showed that efficacy was not compromised by reducing bortezomib
to once weekly in the context of bortezomib use in three or four drug
combination regimens. Recently in a phase 3 randomized controlled trial
(Moreau et al. Lancet Oncol. 2011;12(5):431–440) I.V bortezomib was