FEATURES
approximately 80%. 9
“Not only is this better than with chemoimmunother-
apy, it is multiple logs better than chemoimmunother-
apy,” Dr. O’Brien said. “Although this is still a high-risk
population, [their prognosis] looks a lot more favorable in
a frontline setting [with ibrutinib].”
Dr. Stilgenbauer agreed that chemoimmunotherapy
is not an option in patients with del17p, again citing
data from the CLL14 trial and the availability of other,
non-ibrutinib options for these patients. In patients with
del17p or TP53 mutation, venetoclax + obinutuzumab
improved PFS outcomes, compared with chlorambucil
+ obinutuzumab. In addition, the longer treatment-free
interval after use of the novel combination allows for
potential re-treatment with venetoclax-based therapy.
“This leaves the ibrutinib option in [a clinician’s] back
pocket,” Dr. Stilgenbauer added. “We have more options
for patients with del17p and no clear-cut evidence about
which non-chemoimmunotherapy agent – either ibruti-
nib or venetoclax – should be the preferred option in the
frontline setting.”
Both panelists agreed that, given the increased number
of options available, including targeted therapy, this is an
exciting time in the management of CLL. Several unresolved
issues remain though, not least of which is the need to ad-
dress the high costs of novel agents. —By Leah Lawrence
References
1. Shanafelt TD, Wang XV, Kay NE, et al. Ibrutinib-rituximab or chemoimmunotherapy for chronic
lymphocytic leukemia. N Engl J Med. 2019;381:432-443.
2. Eichorst D, Fink AM, Bahlo J, et al. First-line chemoimmunotherapy with bendamustine and
rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic
lymphocytic leukaemia (CLL10): an international, open-label, randomized, phase 3, non-inferiority
trial. Lancet Oncol. 2016;17:928-942.
3. Rossi D, Terzi-di-Bergamo L, De Paoli L, et al. Molecular prediction of durable remission after
first-line fludarabine-cyclophosphamide-rituximab in chronic lymphocytic leukemia. Blood.
2015;126:1921-1924.
4. Thompson PA, Tam CS, O’Brien SM, et al. Fludarabine, cyclophosphamide, and rituximab treatment
achieves long-term disease-free survival in IGHV-mutated chronic lymphocytic leukemia. Blood.
2016;127:303-309.
5. Moreno C, Greil R, Demirkan F, et al. Ibrutinib plus obinutuzumab versus chlorambucil plus
obinutuzumab in first-line treatment of chronic lymphocytic leukaemia (iLLUMINATE): a
multicenter, randomized, open-label, phase 3 trial. Lancet Oncol. 2019;20:43-56.
6. Woyach JA, Ruppert AS, Heerema NA, et al. Ibrutinib regimens versus chemoimmunotherapy in older
patients with untreated CLL. N Engl J Med. 2018;379:2517-2528.
7. Sharman JP, Banerji V, Fogliatto LM, et al. ELEVATE TN: Phase 3 study of acalabrutinib combined
with obinutuzumab (O) or alone vs O plus chlorambucil (Clb) in patients (pts) with treatment-
naive chronic lymphocytic leukemia (CLL). Abstract #31. Presented at the 2019 ASH Annual
Meeting, December 7, 2019; Orlando, FL.
8. Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and obinutuzumab in patients with CLL and
coexisting conditions. N Engl J Med. 2019;380:2225-2236.
9. Ahn IE, Farooqui MZH, Tian X, et al. Depth and durability of response to ibrutinib in CLL: 5-year
follow-up of a phase 2 study. Blood. 2018;131:2357-2366.
Extinguishing Smoldering Myeloma?
For patients with smoldering myeloma – a precursor stage of
multiple myeloma (MM) – the standard approach for years has
been “watch and wait,” based on the desire to avoid unwanted
toxicities with unnecessary treatment.
“Smoldering myeloma is an older term,” Joshua Richter,
MD, myeloma specialist and assistant professor at the
he Tisch Cancer Institute, Division of Hematology and
Medical Oncology at Mount Sinai Hospital in New York
City, tells ASH Clinical News. “Some groups, including
the Mayo Clinic, have pushed to define this state as
‘asymptomatic myeloma,’ which is probably a better term.
Basically, it means myeloma that we need to monitor but
not to actively treat.”
But, according to Dr. Richter and other myeloma
specialists interviewed by ASH Clinical News, the way
clinicians are viewing so-called smoldering myeloma is
changing. With data from several trials suggesting that
early intervention treatment may prevent progression
to symptomatic MM, there is now a debate among ex-
perts about who to treat, when to begin treatment, and
which drugs or combinations of drugs to use.
10
Focus on Lymphoid & Plasma Cell Malignancies
Expanding the Definition of Multiple Myeloma
MM is the result of progression through two prior clinical
states, a pre-malignant state known as monoclonal gam-
mopathy of undetermined significance (MGUS) and an inter-
mediate stage between MGUS and MM known as smoldering
myeloma. However, progression from MGUS to symptomatic
myeloma is not on a continuous spectrum. Most patients
with MGUS never go on to develop symptomatic myeloma.
Those with smoldering disease have only a 10% risk per year
of disease progression for 5 years, then a 3% risk per year for
the subsequent 5 years, followed by a 1% risk per year.
For years, MM was defined by the presence of four
features, all of which are indicative of the clonal pro-
gression to symptomatic myeloma, known as CRAB:
• hypercalcemia (C)
• renal dysfunction (R)
• anemia (A)
• bone lesions (B)