Page 166 - 2019_11 Resto del Mondo-web

R. Wester et al.
Table 5. Adherence to treatment protocol during induction and consol- idation.
due to its availability and low costs, and offers an excel- lent alternative to treatment with lenalidomide.
Recently, several trials have been performed in patients with NDMM, using alternative schedules for induction and consolidation. The Intergroupe Francophone du Myélome (IFM) performed a phase II trial of lenalidomide combined with bortezomib and dexamethasone (RVD) for induction and consolidation. PFS at three years was 77% and CR was 58%. Most common toxicities were grade 1/2 PN in 55%.22 In the EMN02 trial, VCD for induc- tion was followed by VRD for consolidation treatment. CR rate was 55% and PFS not reached at 60 months.23 Although it should be taken into account that this is a cross comparison between trials, the Carthadex trial effi- cacy data are similar with median PFS of 58 months and CR rate of 63%, and acceptable toxicity. Moreover, the combination of carfilzomib, thalidomide and dexametha- sone is an affordable treatment regimen. These data sug- gest that KTd is an effective and safe induction and con- solidation regimen in newly diagnosed MM.
In conclusion, the combination of carfilzomib, thalido- mide and low-dose dexamethasone appears highly effica- cious and safe in transplant-eligible patients with NDMM across all dose levels with manageable toxicities. Consolidation therapy after ASCT results in a major improvement in response. In addition, we observed that higher dose levels of carfilzomib (36-56 mg/m2) result in better response rates after consolidation therapy. Current studies in newly diagnosed MM patients are performed using 36 mg/m2 twice weekly. The preferred dose to be used in practice would be 36 mg/m2 twice weekly (or 70 mg/m2 once weekly), which we would recommend based on our carthadex response data. Results of cohort 5, in which patients were treated with eight instead of four induction cycles, will follow in the near future.
Further randomized, prospective studies are needed to confirm these data and determine the place for carfil- zomib in the treatment of patients with NDMM.
Acknowledgments
This trial was supported by funding from Onyx Pharmaceuticals, Inc., an Amgen subsidiary.
Kolom1
Carfilzomib
Normal completion
Dose delay, reduction and/or interruption
Premature stop
Thalidomide
Normal completion
Dose delay, reduction and/or interruption
Premature stop
Dexamethasone
Normal completion
Dose delay, reduction and/or interruption
Premature stop
Induction (N=111)
68 (61) 37 (33)
6 (5)
54 (49) 42 (38)
15 (14)a
85 (77) 20 (18)
6 (5)
Consolidation (N=94)
61 (55) 24 (22)
9 (10)
63 (67) 8 (9)
23 (24)b
66 (70) 18 (19)
10 (11)
aIncluding 9 patients who received no thalidomide during induction cycle 4. bIncluding 14 patients who received no thalidomide during consolidation cycle 4. n: number.
hematologic toxicity consisted of infections, respiratory, skin, and vascular disorders. The rate of cardiac AE was low in this trial. Five patients (5%) experienced grade 3 cardiac AE, including congestive heart failure, dyspnea and chest pain. This is comparable to other trials investi- gating carfilzomib in NDMM.12-14 The rate of grade 3/4 car- diac toxicity is slightly higher in RRMM, most likely because patients are older and due to previous treat- ment.9,10 However, the limited number of patients pre- clude firm conclusions about safety regarding cardiac events between the different dose levels. Jakubowiak et al. performed a phase I/II trial of carfilzomib combined with lenalidomide and dexamethasone (CRd). In this trial, patients not proceeding to ASCT continued treatment with CRd beyond eight cycles with a median of 12 cycles. PFS at 24 months was 92%.12 However, thalidomide remains a valuable treatment option in many countries,
References
1. Lahuerta JJ, Mateos MV, Martinez-Lopez J, et al. Influence of pre- and post-transplanta- tion responses on outcome of patients with multiple myeloma: sequential improvement of response and achievement of complete response are associated with longer sur- vival. J Clin Oncol. 2008;26(35):5775-5782.
2. Cavo M, Brioli A, Tacchetti P, et al. Role of consolidation therapy in transplant eligible multiple myeloma patients. Semin Oncol. 2013;40(5):610-617.
3. Niesvizky R, Richardson PG, Rajkumar SV, et al. The relationship between quality of response and clinical benefit for patients treated on the bortezomib arm of the inter- national, randomized, phase 3 APEX trial in relapsed multiple myeloma. Br J Haematol. 2008;143(1):46-53.
4. Harousseau JL, Dimopoulos MA, Wang M,
et al. Better quality of response to lenalido- mide plus dexamethasone is associated with improved clinical outcomes in patients with relapsed or refractory multiple myelo- ma. Haematologica. 2010;95(10):1738-1744.
5. van de Velde HJ, Liu X, Chen G, et al. Complete response correlates with long- term survival and progression-free survival in high-dose therapy in multiple myeloma. Haematologica. 2007;92(10):1399-1406.
and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHE- MA/GEM study. Blood. 2012;120(8):1589- 1596.
8. Moreau P, Hulin C, Macro M, et al. VTD is superior to VCD prior to intensive therapy in multiple myeloma: results of the prospec- tive IFM2013-04 trial. Blood. 2016; 127(21):2569-2574.
9. Stewart AK, Rajkumar SV, Dimopoulos MA, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015;372(2):142-
6. Cavo M, Tacchetti P, Patriarca F, et al. Bortezomib with thalidomide plus dexam-
ethasone compared with thalidomide plus dexamethasone as induction therapy
before, and consolidation therapy after, 152.
double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet. 2010; 376(9758):2075-2085.
7. Rosinol L, Oriol A, Teruel AI, et al. Superiority of bortezomib, thalidomide,
10. Dimopoulos MA, Moreau P, Palumbo A, et al. Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study.
2272
haematologica | 2019; 104(11)