A randomised comparison of melphalan with prednisone or dexamethasone as induction therapy and dexamethasone or observation as maintenance therapy in multiple myeloma: NCIC CTG MY.7

Shustik, Chaim; Belch, Andrew R.; Robinson, Sue; Rubin, Sheldon; Dolan, Sean; Kovacs, Michael J.; Grewal, Kuljit; Walde, David; Barr, Robert M.; Wilson, Jonathan; Gill, Kulwant; Vickars, Linda M.; Rudinskas, Leona; Sicheri, D; Wilson, Kenneth S.; Djurfeldt, Marina; Shepherd, Lois E.; Ding, Keyue; Meyer, Ralph M.

doi:10.1111/j.1365-2141.2006.06405.x

Cited by 77 publications

(54 citation statements)

References 23 publications

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“…Thus, different maintenance strategies have emerged which attempt to prolong the duration of an initial or subsequent response. Early studies of maintenance therapy employing melphalan, 36,37 interferon 38-40 or corticosteroid 41,42 treatment often prolonged EFS, but not OS, and had substantial morbidity. Since ineffective maintenance strategies not only fail to benefit patients, but also bring additional cost, morbidity and reduced quality of life, these therapies are not routinely applied.…”

Section: Maintenance Therapymentioning

confidence: 99%

Clinically relevant end points and new drug approvals for myeloma

et al. 2007

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This manuscript summarizes the recommendations of the American Society of Hematology/US Food and Drug Administration Workshop on Clinical Endpoints in Multiple Myeloma, which brought together clinical investigators in multiple myeloma, the United States Food and Drug Administration, pharmaceutical companies, patient advocates and other concerned scientists and physicians to provide guidance, consensus and consistency in the definition of clinically relevant end points to expedite new drug approvals for multiple myeloma in the appropriate trial design settings. This manuscript will therefore be a most valuable resource to provide the framework for the design of appropriate clinical trial strategies for more rapid new drug approval in myeloma.

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Section: Maintenance Therapymentioning

confidence: 99%

Clinically relevant end points and new drug approvals for myeloma

et al. 2007

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“…3 Corticosteroids in high doses were shown to prolong the duration of the maintenance phase, but results concerning overall survival (OS) were controversial. 4,5 Interferon α-2b (IFN) exerts direct anti-myeloma activity 6 but yielded inconsistent results when tested as maintenance treatment. Two meta-analyses, one on individual patient data 7 and another on published results, 8 showed a marginal but statistically significant gain in both maintenance duration and overall survival.…”

Section: Introductionmentioning

confidence: 99%

Thalidomide maintenance treatment increases progression-free but not overall survival in elderly patients with myeloma

Ludwig¹,

Adam²,

Tóthová³

et al. 2010

Haematologica

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BackgroundThalidomide maintenance therapy after stem cell transplantation resulted in increased progression-free survival and overall survival in a few trials, but its role in non-transplant eligible patients with multiple myeloma remains unclear. This study assessed the impact of thalidomide-interferon in comparison to interferon maintenance therapy in elderly patients with multiple myeloma. Design and MethodsOf 289 elderly patients with multiple myeloma who were randomized to thalidomide-dexamethasone or melphalan-prednisolone induction therapy, 137 finally completed 9 cycles of induction therapy with stable disease or better and thereby qualified for maintenance treatment. Of these, 128 have been randomized to either thalidomide-interferon or interferon alone. Primary study endpoints were progression-free survival and response rates; secondary endpoints were overall survival, toxicity and quality of life. ResultsThalidomide-interferon maintenance therapy led to a significantly longer progression-free survival compared to interferon (27.7 vs. 13.2 months, P=0.0068), but overall survival was similar in both groups (52.6 vs. 51.4 months, P=0.81) and did not differ between patients aged 75 years or older, or younger patients (P=0.39). Survival after disease progression tended to be shorter in patients on thalidomide-interferon maintenance therapy (P=0.056). Progression-free survival and overall survival tended to be shorter in patients with adverse cytogenetic (FISH) findings compared to the standard risk group but differences were not significant (P=0.084 and P=0.082, respectively). Patients on thalidomide-interferon presented with more neuropathy (P=0.0015), constipation (P=0.0004), skin toxicity (P=0.0041) and elevated creatinine (P=0.026). ConclusionsThalidomide plus interferon maintenance therapy increased progression-free survival but not overall survival and was associated with slightly more toxicity than maintenance with interferon alone. (ClinicalTrials.gov Identifier: NCT00205751).Key words: thalidomide, thalidomide-interferon, progression-free survival, overall survival. Haematologica 2010;95(9):1548-1554. doi:10.3324/haematol.2009 This is an open-access paper. Citation: Ludwig H, Adam Z, Tóthová E, Hajek R, Labar B, Egyed M, Spicka I, Gisslinger H, Drach J, Kuhn I, Hinke A, and Zojer N.Thalidomide maintenance treatment increases progression-free but not overall survival in elderly patients with myeloma.Thalidomide maintenance treatment increases progression-free but not overall survival in elderly patients with myeloma

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“…Maintenance treatments with alkylating agents, steroids or interferon were tested in the pre-novel agents era (38)(39)(40)(41). In one study, maintenance with prednisone every other day improved PFS and OS, (38) yet, in another study, no benefit was seen with single agent dexamethasone.…”

Section: Maintenance Regimensmentioning

confidence: 99%

“…In one study, maintenance with prednisone every other day improved PFS and OS, (38) yet, in another study, no benefit was seen with single agent dexamethasone. (39) Data are therefore insufficient to recommend corticosteroids maintenance therapy.…”

Section: Maintenance Regimensmentioning

confidence: 99%

The Role of Pre-Transplant Induction Regimens and Autologous Stem Cell Transplantation in the Era of Novel Targeted Agents

Gay

Cavallo

Palumbo

2015

Drugs

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Outcome of patients with multiple myeloma (MM) has greatly improved with the use of autologous stem cell transplantation (ASCT) and new agents, such as immunomodulatory drugs (thalidomide and lenalidomide) and proteasome inhibitors (bortezomib). When compared to conventional chemotherapy, high-dose melphalan with ASCT significantly improved response rates and progression-free survival, while overall survival benefit was not consistent across all trials. ASCT is considered the standard treatment for patients who are younger than 65 years and who do not have limiting comorbidities. New, effective agents have been introduced as part of induction, consolidation and maintenance treatments within ASCT and in combinations with chemotherapy for patients not eligible for ASCT. The remarkable results obtained with these regimens are questioning the role of ASCT for newly diagnosed MM patients. This article aims to delineate the role of ASCT in the era of novel agents based on the results of recent clinical trials. 1.IntroductionAutologous stem cell transplantation (ASCT) is the standard treatment for newly diagnosed multiple myeloma (MM) patients younger than 65 years and/or eligible for high-dose chemotherapy. Before the introduction of novel agents, such as immunomodulatory drugs (IMiDs; thalidomide and lenalidomide) and proteasome inhibitors (bortezomib), high-dose melphalan with ASCT significantly improved response rates and progression-free survival (PFS) in comparison with conventional chemotherapy, with conflicting results in terms of overall survival (OS) (1-4).Newer agents were later incorporated both in the transplant and non-transplant settings, and significantly improved patient outcome (5). The depth and the duration of response obtained with these new approaches correlated with a PFS benefit and, in several studies, also with an OS improvement. This was evident in both young patients receiving ASCT, and elderly patients receiving conventional chemotherapy in combination with new agents (6-10). It has been suggested that the optimal treatment strategy should aim at achieving sustained complete response (CR) (11).Yet, long-term control of the disease has been shown also in patients not achieving high-quality responses, which may reflect changes in host immune status or a clonal heterogeneity of the disease at diagnosis. Thus patients may also benefit from a less intensive treatment, that can be able to control, if not eradicate, the disease. The remarkable results obtained in the non-transplant setting questioned the role of ASCT for newly diagnosed MM patients. On the other hand, there is increasing evidence that the selective pressure of treatment may be responsible for emergence of different MM sub-clones leading to drug resistance at more advanced stages (12). If this will be confirmed, it could be reasonable to give the most effective and intensive treatment, that is ASCT, at the early phases of disease, when the probability of reaching long-lasting remissions is higher.This article aims to deline...

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A randomised comparison of melphalan with prednisone or dexamethasone as induction therapy and dexamethasone or observation as maintenance therapy in multiple myeloma: NCIC CTG MY.7

Cited by 77 publications

References 23 publications

Clinically relevant end points and new drug approvals for myeloma

Clinically relevant end points and new drug approvals for myeloma

Thalidomide maintenance treatment increases progression-free but not overall survival in elderly patients with myeloma

The Role of Pre-Transplant Induction Regimens and Autologous Stem Cell Transplantation in the Era of Novel Targeted Agents

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