NcXHF

SEQUENCING MYELOMA TREATMENTS
with other anti-MM treatments and its use in earlier lines
of treatment. 32
CARFILZOMIB
Carfılzomib initially was evaluated in patients with very advanced
MM. In the single-arm phase II study PX-171-003-
A1, the treatment of patients with relapsed and refractory
MM with single-agent carfılzomib led to durable responses,
resulting in an ORR of 23.7%, a median DOR of 7.8 months,
and a median OS of 15.6 months. 48 Furthermore, the phase II
study PX-171-004 examined carfılzomib in patients with relapsed
and/or refractory MM who were treated previously
with bortezomib and in patients who were bortezomibnaive.
49,50 In patients previously treated with bortezomib, the
ORR was 17.1%, with a median DOR of more than10.6
months and a median TTP of 4.6 months, 50 whereas in 126
response-evaluable bortezomib-naive patients, an ORR of
47.6% and a median TTP of 12.0 months were seen. 49 The
lower ORR in patients previously treated with bortezomib
may be attributable to a subset of patients who developed resistance
to the class of PIs.
Both the PX-171-003-A1 and PX-171-004 trials examined
a target dose of 27 mg/m 2 of carfılzomib. Higher doses of
carfılzomib have been examined in phase Ib/II studies and
appear to be associated with an increased likelihood of
achieving a clinical response. 32 However, this requires confırmation
in further trials. Thus far, doses higher than those
recommended in the label have not been examined in patients
with relapsed and refractory disease.
CONCLUSION
The tremendously active research into treatments for MM
has resulted in a number of highly active new agents and encourages
optimism to the goal of transforming MM into a
chronic disease. Although none of the agents with novel
mechanisms of action (those following the PIs or IMiDs) are
yet to be approved, it is reasonable to believe that several will
be in the near future. Our task will be to defıne the optimal
sequence of treatment, the optimal combinations both for
front-line and relapsed myeloma, according to age, comorbidities,
cost, drug availability, and patients’ choice.
Disclosures of Potential Conflicts of Interest
Relationships are considered self-held and compensated unless otherwise noted. Relationships marked “L” indicate leadership positions. Relationships marked “I” are those held by an immediate
family member; those marked “B” are held by the author and an immediate family member. Institutional relationships are marked “Inst.” Relationships marked “U” are uncompensated.
Employment: None. Leadership Position: None. Stock or Other Ownership Interests: None. Honoraria: None. Consulting or Advisory Role: None.
Speakers’ Bureau: None. Research Funding: Cyrille Touzeau, Abbvie (Inst). Patents, Royalties, or Other Intellectual Property: None. Expert
Testimony: None. Travel, Accommodations, Expenses: None. Other Relationships: None.
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