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IMP phase I/II study in transplant-ineligible NDMM
A
B
NDMM.14,16,17,19,23,32,33 The CR+VGPR rates post-IMP (43%) and overall (48%) are comparable to rates reported for VMP (41–50% in the phase III VISTA, GIMEMA-MM-03-05, and ALCYONE trials17,19,33), and median PFS (22.1 months) also appeared similar to that reported with VMP and carfilzomib-MP (18.1–27.3 months).17,19,23,33 Similar CR+VGPR rates (47–49%) and median PFS (21–26 months) were seen with fixed-duration and continuous lenalidomide-dexamethasone (Rd) in the FIRST phase III trial in transplant-ineligible NDMM,35 and while responses and outcomes appeared better with daratumumab-VMP in ALCYONE (71% CR+VGPR, 18-month PFS 71.6%),33 and with IRd (58–63%, median PFS 29.4–35.4 months)29 and bortezomib-Rd (44%, median PFS 43 months) in NDMM patients,36 these differences should be considered in the context of the addition of daratumumab as a fourth induction agent and as maintenance therapy in ALCYONE, and the inclusion of a high proportion of transplant-eligible patients in the
Figure 2. Kaplan-Meier analysis of PFS and OS. (A) PFS for the total patient population in the overall study (induction and maintenance phases) and in patients who went on to receive maintenance, and (B) OS in the overall study, for the total safety population and the subset of patients treated at the RP2D (4.0 mg) in Arm B. OS: overall survival; PFS: progression-free survival; RP2D: recom- mended phase II dose. Figure 2A, one patient in the RP2D group with PD entered maintenance, the patient was iden- tified later following reassessment of the data.
IRd (35%)29 and VRd (69%) studies.36 The overall CR rate (28%) seen with IMP plus ixazomib maintenance was also comparable to those reported for VMP without maintenance (24–33%17,19,23,33). Although the post-IMP induction CR rate was lower than that reported for VMP in the VISTA study (13% vs. 31%), the CR rate increased to 28% during maintenance. This difference may simply reflect the longer median time to CR observed with IMP (11.6 months, compared with 4.2 months for VMP in the VISTA study).17 Indeed, the time to first response with IMP (1.7 months) was similar to that seen in the VISTA study (1.4 months). These findings together suggest that the response with IMP may mature over a longer period compared with VMP and similar response rates can be achieved with IMP followed by ixazomib maintenance and VMP without maintenance.17,19,23,33 It should also be noted that the weekly IMP regimen used at the RP2D was similar to the less-intense weekly VMP regimen used in the PETHEMA/GEM05 study, followed by bortezomib- based maintenance.14 In the overall study, the CR rate
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