NcXHF

SEQUENCING MYELOMA TREATMENTS
TABLE 1. Recent and Ongoing Phase III Trials in Relapsed Multiple Myeloma: Two- versus Three-Drug
Combinations
No. of Patients ORR ( PR) (%) Median PFS (mo) OS
IFM 2005-04/MMVAR 35
TD 134 72 13.6 24 mo, 65%
VTD 135 88 18.3, p 0.001 71%, p 0.09
PANORAMA 1 36
VD 387 54.6 8.08 Median 30.4
VD-Panobinostat 381 60.7, p 0.09 11.99, p 0.0001 33.6, p 0.26
MM007 (NCT 01734928)
VD NA NA NA NA
VD-Pomalidomide
ASPIRE 37
Rd 396 66.7 17.6 24 mo, 65%
Rd-Carfilzomib 396 87.1, p 0.001 26.3, p 0.0001 73.3%, p 0.04
ELOQUENT-2 (NCT01239797)
Rd NA NA NA NA
Rd-Elotuzumab
POLLUX-MMY3003 (NCT02076009) NA NA NA NA
Rd
Rd-Daratumumab
TOURMALINE-1 (NCT61564537) NA NA NA NA
Rd
Rd-Ixazomib
Abbreviations: ORR: overall response rate, PR: partial response; PFS: progression-free survival; mo, months; OS: overall survival; TD: thalidomide-dexamethasone; VTD: bortezomib-thalidomidedexamethasone;
VD: bortezomib-dexamethasone; Rd: lenalidomide-dexamethasone; NA, not available.
nation was associated with more gastrointestinal toxicities,
thrombocytopenia, and fatigue compared to VD. In the second
recently reported phase III ASPIRE study, in which Rd was prospectively
compared to Rd-carfılzomib, 43% of the patients were
treated in fırst relapse of disease, whereas 56% had received a
prior transplant. 37 This trial showed that the addition of intravenous
carfılzomib to Rd resulted in a substantially improved
PFS (median, 26.3 vs. 17.6 months in the control group); this
was observed across all predefıned subgroups. Rd-carfılzomib
had a favorable risk-benefıt profıle and patients in the carfılzomib
group reported a superior health-related QOL.
Triplet combinations at fırst relapse probably will become
standard in the near future, but the benefıt in terms of overall
response rate (ORR) and PFS will have to be balanced with
cost and toxicity. Overall survival as a secondary endpoint
also is important. In the setting of relapsed disease, the results
of ongoing trials investigating other classes of agents, such as
the monoclonal antibodies, are eagerly awaited. Although
elotuzumab, which targets SLAMF7, lacks activity as a single
agent in relapsed myeloma, an ORR of 82% and more than 30
months PFS was reported when this agent was combined
with Rd in a phase II trial. 38 These results were the basis of the
ongoing ELOQUENT-2 trial that is prospectively comparing
Rd versus Rd-elotuzumab in patients whose disease had relapsed.
The same design also was selected for the prospective
comparison of Rd versus Rd-daratumumab in the ongoing
phase III randomized trial POLLUX. Daratumumab, a monoclonal
antibody targeting CD38, has shown impressive activity
as a single agent in patients with advanced disease 39 and in combination
with Rd in phase II trials. 40 Another monoclonal antibody
targeting CD38, SAR650984, currently is also being
developed in relapsed disease. 41 A further phase III trial using
Rd as a control arm could change the treatment landscape of
relapsed myeloma. The placebo-controlled TOURMALINE-
MM1 study is currently comparing Rd versus Rd-ixazomib in
patients with relapsed disease. This combination also was tested
along with Rd as front-line treatment in a phase II study resulting
in impressive response rates. 42 The all-oral triplet combination
Rd-ixazomib could become a convenient rescue treatment,
provided that toxicity in relapse is similar to that observed in the
front-line setting. VD is, as mentioned above, another backbone
regimen in relapsed myeloma, and this combination also is currently
being compared to VD plus pomalidomide in a prospective
phase III international trial.
RELAPSED MULTIPLE MYELOMA IN PATIENTS NOT
PREVIOUSLY TREATED WITH ASCT
As discussed previously, the front-line treatment of older patients
in 2015/2016 consists of VMP, Rd, and, to a lesser extent,
MPT. If their disease relapses, patients may either repeat
the initial therapy—if this treatment had a fıxed duration and
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