Bortezomib and thalidomide maintenance after stem cell transplantation for multiple myeloma: a PETHEMA/GEM trial

Abstract

The phase III trial GEM05MENOS65 randomized 390 patients 65 years old or younger with newly diagnosed symptomatic multiple myeloma (MM) to receive induction with thalidomide/dexamethasone, bortezomib/thalidomide/dexamethasone and Vincristine, BCNU, melphalan, cyclophosphamide, prednisone/vincristine, BCNU, doxorubicin, dexamethasone bortezomib (VBMCP/VBAD/B) followed by autologous stem cell transplantation (ASCT) with MEL-200. After ASCT, a second randomization was performed to compare thalidomide/bortezomib (TV), thalidomide (T) and alfa-2b interferon (alfa2-IFN). Maintenance treatment consisted of TV (thalidomide 100 mg daily plus one cycle of intravenous bortezomib at 1.3 mg/m on days 1, 4, 8 and 11 every 3 months) versus T (100 mg daily) versus alfa2-IFN (3 MU three times per week) for up to 3 years. A total of 271 patients were randomized (TV: 91; T: 88; alfa2-IFN: 92). The complete response (CR) rate with maintenance was improved by 21% with TV, 11% with T and 17% with alfa2-IFN (P, not significant). After a median follow-up of 58.6 months, the progression-free survival (PFS) was significantly longer with TV compared with T and alfa2-IFN (50.6 vs 40.3 vs 32.5 months, P=0.03). Overall survival was not significantly different among the three arms. Grade 2-3 peripheral neuropathy was observed in 48.8%, 34.4% and 1% of patients treated with TV, T and alfa2-IFN, respectively. In conclusion, bortezomib and thalidomide maintenance resulted in a significantly longer PFS when compared with thalidomide or alfa2-IFN. (no. EUDRA 2005-001110-41).

Retrospective analysis of the efficacy and influencing factors of autologous hematopoietic stem cell transplantation for multiple myeloma

“…VGPR was obtained after transplantation, the regimen of bortezomib combined with thalidomide was given, the disease did not progress, and the patient survived. This suggests that the application of the new drug and maintenance therapy after transplantation further improved the efficacy in this patient, and the present study confirmed that the consolidation and maintenance of bortezomib combined with thalidomide after transplantation in MM patients can significantly increase the 3‐year PFS rate of patients …”

Ixazomib maintenance therapy in newly diagnosed multiple myeloma: An integrated analysis of four phase I/II studies

“…There is increasing evidence for the clinical benefit of long-term, continuous therapy in patients with newly diagnosed multiple myeloma (NDMM), irrespective of whether they undergo autologous stem cell transplantation (ASCT). [1][2][3][4][5][6][7][8] Studies suggest that patients with NDMM who receive continuous treatment until first disease progression have prolong ed progression-free (PFS) and overall (OS) survival vs those who receive fixed-duration therapy, 1,8,9 although across studies the OS b enefits associated with prolonged treatment were not consistent a nd may have been less pronounced than the observed PFS improvem ents. 1,6,10 Lenalidomide is the only agent currently approved in the United States and EU for use as maintenance therapy; however, it is only approved following ASCT in patients with NDMM.…”

“…11,12 Proteasome inhibitors (PIs) are a cornerstone of therapy for many patient s with multiple myeloma (MM). 13,14 Maintenance with bortezomib has been extensively studied and has demonstrated PFS improvements 2,7 ; however, long-term treatment with bortezomib may be limit ed due to toxicity and the need for regular parenteral administration, which can increase treatment burden. 7,[15][16][17][18][19] Ixazomib is the first oral PI to be approved for MM, for use in combination with lenalidomide-dexamethasone (Rd) in patients with MM who have received ≥ 1 p rior therapy.…”

“…13,14 Maintenance with bortezomib has been extensively studied and has demonstrated PFS improvements 2,7 ; however, long-term treatment with bortezomib may be limit ed due to toxicity and the need for regular parenteral administration, which can increase treatment burden. 7,[15][16][17][18][19] Ixazomib is the first oral PI to be approved for MM, for use in combination with lenalidomide-dexamethasone (Rd) in patients with MM who have received ≥ 1 p rior therapy. 20 The convenience of oral administration and the established safety profile of ixazomib suggest a potential for extended dosing, 16,21,22 and indeed, single-agent maintenance with ixazomib for up to 24 months in post-ASCT patients with NDMM has demonstrated a significant improvement in PFS, after standardof-care induction.…”

Bortezomib consolidation following autologous transplant in younger and older patients with newly diagnosed multiple myeloma in two phase III trials

“…With the aim of improving long-term outcomes post-transplant, consolidation therapy and longer-term maintenance therapy with novel agents, particularly proteasome inhibitors and immunomodulatory drugs, have been investigated. [3][4][5][6][7] Studies conducted to date indicate that fixed-term, bortezomib-based consolidation therapy can be used to improve responses after ASCT, while prolonging progression-free survival (PFS). 4 8 The proportion of patients reaching a very good partial response or better (≥VGPR) was also greater in the bortezomib arm vs the observation arm at study end (62% vs 48%; P = 0.003), and single-agent bortezomib consolidation as given in our two trials appeared generally well tolerated.…”