A phase 2 study of three low-dose intensity subcutaneous bortezomib regimens in elderly frail patients with untreated multiple myeloma

Abstract

54This phase 2 trial evaluated 3 low-dose intensity subcutaneous bortezomib-based treatments in 55 patients ≥75 years with newly diagnosed multiple myeloma (MM). Patients received subcutaneous 56 bortezomib plus oral prednisone (VP, N=51) or VP plus cyclophosphamide (VCP, N=51) or VP plus 57 melphalan (VMP, N=50), followed by bortezomib maintenance, and half of the patients were frail. 58Response rate was 64% with VP, 67% with VCP and 86% with VMP, very good partial response 59 rate or better was 26%, 28.5% and 49%, respectively. Median PFS was 14.0, 15.2 and 17.1 and 2-60 year OS was 60%, 70% and 76%, in VP, VCP, VMP respectively. At least one drug-related grade 61 ≥3 non-hematologic adverse event (AE) occurred in 22% of VP, 37% of VCP and 33% of VMP 62 patients; the discontinuation rate for AEs was 12%, 14% and 20% and the 6-month rate of toxicity-63 related deaths was 4%, 4% and 8%, respectively. The most common grade ≥3 AEs included 64 infections (8-20%), constitutional (10-14%) and cardiovascular events (4-12%); peripheral 65 neuropathy was limited (4-6%). Bortezomib maintenance was effective and feasible. 66 VP, VCP and VMP regimens demonstrated no substantial difference. Yet, toxicity was higher with 67 VMP, suggesting that a two-drug combination followed by maintenance should be preferred in frail 68

Addition of cyclophosphamide and higher doses of dexamethasone do not improve outcomes of patients with AL amyloidosis treated with bortezomib

“…Two prospective randomized studies in elderly frail myeloma patients have also shown that adding either cyclophosphamide or melphalan or thalidomide to bortezomib and dexamethasone does not offer significant benefit in terms of response rates and progression-free survival, although it increases toxicity. 13, 14 Triple combinations are considered the standard for induction in younger, transplant eligible myeloma patients, 22 but our data and the data from elderly frail myeloma patients show that it is difficult to extrapolate the results from studies in fitter patients and apply them in frail patients, such as those with AL amyloidosis.…”

“…13, 14 For patients with AL amyloidosis, the combination of VCD is considered as a ‘standard’ regimen for primary therapy in most centers, 1, 15, 16 but it is not clear whether the addition of a third drug (cyclophosphamide) to the bortezomib/dexamethasone (VD) backbone further and significantly improves efficacy, given the substantial activity of bortezomib itself. Also, it is not clear whether cyclophosphamide is the optimal partner of VD, among other potential partners, including other alkylating agents.…”

Addition of Cyclophosphamide and Higher Doses of Dexamethasone Do Not Improve Outcomes of Patients With AL amyloidosis Treated With Bortezomib

“…Two prospective randomized studies in elderly frail myeloma patients have also shown that adding either cyclophosphamide or melphalan or thalidomide to bortezomib and dexamethasone does not offer significant benefit in terms of response rates and progression-free survival, although it increases toxicity. 13,14 Triple combinations are considered the standard for induction in younger, transplant eligible myeloma patients, 22 but our data and the data from elderly frail myeloma Figure 1. OS of patients treated with VD or VCD (all patients).…”

“…13,14 For patients with AL amyloidosis, the combination of VCD is considered as a 'standard' regimen for primary therapy in most centers, 1,15,16 but it is not clear whether the addition of a third drug (cyclophosphamide) to the bortezomib/dexamethasone (VD) backbone further and significantly improves efficacy, given the substantial activity of bortezomib itself. Also, it is not clear whether cyclophosphamide is the optimal partner of VD, among other potential partners, including other alkylating agents.…”

How I treat first relapse of myeloma

“…[57][58][59] But in frail elderly patients, the benefit of triplets is less evident because they may be more toxic, particularly with regard to hematologic toxicity. [89][90][91] Therapeutic strategies should be defined after careful assessment of the frailty profile. Doses and mode of administration should be adapted.…”