TRAINING and EDUCATION
How I Treat In Brief
Recently, Sara Gandolfi, MD; Claudia Paba Prada, MD; and Paul G. Richardson, MD, discussed the treatment of
younger patients with multiple myeloma, balancing disease control with the effects on quality of life. Below, we
summarize their approach.
This material was repurposed from “How I treat the young patient with multiple myeloma,” published in the
September 13, 2018, edition of Blood.
Treating the Young Patient With Multiple Myeloma
Multiple myeloma (MM) is rare in people
younger than 30 years, with a median age at
diagnosis of 70 years; however, 37 percent of
patients diagnosed with MM are younger than
65 years. For these “younger patients,” the issue
of optimal treatment strategies is especially
germane, with the goal being to improve long-
term outcomes while minimizing the impact of
treatment-related toxicities.
Here, we provide a practical approach to
the management of younger patients (<65
years) with newly diagnosed MM, with a focus
on novel treatment approaches, including im-
munomodulatory drugs (IMiDs), proteasome
inhibitors (PIs), and monoclonal antibodies.
When to Start Treatment
The definition of active MM relies on clinico-
pathologic criteria that require evidence of
end-organ damage attributable to the underlying
clonal plasma cell disorder. We treat patients
with active MM per the revised 2014 Inter-
national Myeloma Working Group (IMWG)
criteria, which requires the presence of at least
one myeloma-defining event and three specific
biomarkers ( TABLE ).
Further research is required to identify
markers of disease progression in patients with
smoldering MM (SMM), so we counsel young-
er patients with SMM who are eligible for
early intervention to consider participation in
Revised International
Staging System for MM
TABLE.
R-ISS
stage
Risk Stratification
Given the heterogeneity of MM, risk strati-
fication is a challenge. Several studies have
validated multiple biologic factors influencing
risk and prognosis in MM, and we recommend
both the International Staging System (ISS)
and the Revised ISS (R-ISS) prognostic scores.
ISS is a simple tool that includes β2-
microglobulin, serum albumin, and information
on tumor burden and disease impact on the
host; the R-ISS adds cytogenetic abnormalities
detected by fluorescence in situ hybridization
(FISH) and lactate dehydrogenase (LDH) to the
ISS to stratify patients with newly diagnosed
MM into three risk groups. In addition, host-
related factors, such as age, performance status,
comorbidities, and frailty, should be considered
when choosing treatment strategy.
Choice of Initial Treatment
The incorporation of novel agents in MM
treatment has resulted in a major improve-
ment in overall survival (OS), with induction
regimens containing three or more drugs
(including PIs and IMiDs) appearing to be
the best choice for initial therapy. Our pro-
posed guidelines for the management of MM
FIGURE.
patients is presented in the FIGURE .
In our practice, patients who are not
eligible for or decline to participate in a
clinical trial are treated with lenalidomide,
bortezomib, dexamethasone (RVD) for six
to eight cycles as initial treatment or other
combinations, followed by hematopoietic
cell collection; autologous hematopoietic cell
transplantation (AHCT) also is considered,
with maintenance to follow.
Another combination to be considered is
cyclophosphamide, bortezomib, dexamethasone
(CyBorD), although a recent randomized
trial found that the triplet regimen contain-
ing a PI and an IMiD is superior to CyBorD.
However, this regimen is particularly use-
ful and part of our practice in patients with
acute renal failure. Similarly, in patients with
underlying neuropathy, we favor carfilzomib,
lenalidomide, dexamethasone (KRD), given
its minimal neurotoxicity and remarkable effi-
cacy. This regimen may be especially valuable
in younger patients at a lower risk for vascular
toxicity and cardiac complications.
The Role of Transplant
High-dose chemotherapy followed by AHCT
is still considered a standard of care in eligible
patients with newly diagnosed MM, but the
depth and duration of response achieved with
Continued on page 34
Proposed Guidelines for Management of Younger Patients With MM
Younger patients with newly diagnosed MM
Criteria
ISS, R-ISS, comorbidity assessment
All of the following:
• Serum albumin ≥3.5 g/dL
• Serum β2-microglobulin <3.5 mg/L
• No high-risk chromosomal
abnormalities
• Normal serum LDH level
II Not R-ISS stage I or III
III Both of the following:
• Serum β2-microglobulin ≥5.5 mg/L
• High-risk chromosomal abnormalities
by interphase FISH or high LDH
No comorbidities
Renal impairment
Peripheral neuropathy
Consider clinical trials
Induction
RVD
KRD
Consider CyBorD
Favor KRD if no
cardiovascular risk factors;
IRD if feasible
Hematpoietic cell collection – consider AHCT followed by consolidation
Continuous
therapy/
maintenance
Lenalidomide-based
maintenance;
consider adding
bortezomib
Lenalidomide-based
maintenance if renal
function recovered;
consider adding
bortezomib
Lenalidomide-based
maintenance;
consider adding ixazomib;
consider bortezomib, if PN
recovered
I
clinical trials as part of their overall treatment
strategy, together with careful observation and
the use of bisphosphonates for bone loss.
CyBorD = cyclophosphamide, bortezomib, dexamethasone; ISS = International Staging System; KRD = carfilzomib, lenalidomide, dexamethasone;
PN = peripheral neuropathy; R-ISS = Revised International Staging System; RVD = lenalidomide, bortezomib, dexamethasone;
IRD = ixazomib, lenalidomide, dexamethasone
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