Chimeric antigen receptor T-cell therapy for multiple myeloma: a consensus statement from The European Myeloma Network

Adoptive cellular therapy using chimeric antigen receptor T-cell (CART) therapy is currently being evaluated in patients with relapsed / refractory multiple myeloma (MM). The majority of CAR-T cell programs now being tested in clinical trials are targeting B-cell maturation antigen. Several recent phase I / II trials show promising preliminary results in patients with MM progressing on proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies targeting CD38. CAR-T cell therapy is a potentially life-threatening strategy that can only be administered in experienced centers. For the moment, CAR-T cell therapy for MM is still experimental, but once this strateg

Insights on multiple myeloma treatment strategies

The introduction of new agents and management strategies over the past decade has resulted in a major step change in treatment outcomes with deepening responses and increased survival for patients with multiple myeloma. In daily clinical practice, healthcare professionals are now faced with challenges including, optimal treatment sequencing and changing treatment goals. In light of this, a group of experts met to discuss diagnostic and treatment guidelines, examine current clinical practice, and consider how new clinical trial data may be integrated into the management of multiple myeloma in the future

Prevention and management of adverse events of novel agents in multiple myeloma: a consensus of the European Myeloma Network

During the last few years, several new drugs have been introduced for treatment of patients with multiple myeloma, which have significantly improved the treatment outcome. All of these novel substances differ at least in part in their mode of action from similar drugs of the same drug class, or are representatives of new drug classes, and as such present with very specific side effect profiles. In this review, we summarize these adverse events, provide information on their prevention, and give practical guidance for monitoring of patients and for management of adverse events

Prevention and management of adverse events of novel agents in multiple myeloma: A consensus of the European Myeloma Network

During the last few years, several new drugs have been introduced for treatment of patients with multiple myeloma, which have significantly improved the treatment outcome. All of these novel substances differ at least in part in their mode of action from similar drugs of the same drug class, or are representatives of new drug classes, and as such present with very specific side effect profiles. In this review, we summarize these adverse events, provide information on their prevention, and give practical guidance for monitoring of patients and for management of adverse events

Treatment-related peripheral neuropathy in multiple myeloma: the challenge continues

Introduction of the proteasome inhibitor bortezomib and the immunomodulatory drugs thalidomide and lenalidomide has substantially improved outcomes for patients with multiple myeloma. As a result, these drugs have become cornerstones of current antimyeloma treatment regimens. However, after several years of clinical experience it has become apparent that peripheral neuropathy is the most common and potentially disabling non-haematological side-effect associated with thalidomide and bortezomib. Maximising treatment benefit while preserving quality of life therefore requires a careful balance between achieving optimum activity and minimising toxicity, including neuropathy, to further enhance efficacy. In this review, we discuss all aspects of drug-induced peripheral neuropathy in myeloma, with a particular focus on thalidomide and bortezomib. © 2010 Elsevier Ltd

Lenalidomide in combination with dexamethasone at first relapse in comparison with its use as later salvage therapy in relapsed or refractory multiple myeloma

This subset analysis of data from two phase III studies in patients with relapsed or refractory multiple myeloma (MM) evaluated the benefit of initiating lenalidomide plus dexamethasone at first relapse. Multivariate analysis showed that fewer prior therapies, along with β2-microglobulin (≤2.5 mg/L), predicted a better time to progression (TTP; study end-point) with lenalidomide plus dexamethasone treatment. Patients with one prior therapy showed a significant improvement in benefit after first relapse compared with those who received two or more therapies. Patients with one prior therapy had significantly prolonged median TTP (17.1 vs. 10.6 months; P = 0.026) and progression-free survival (14.1 vs. 9.5 months, P = 0.047) compared with patients treated in later lines. Overall response rates were higher (66.9% vs. 56.8%, P = 0.06), and the complete response plus very good partial response rate was significantly higher in first relapse (39.8% vs. 27.7%, P = 0.025). Importantly, overall survival was significantly prolonged for patients treated with lenalidomide plus dexamethasone with one prior therapy, compared with patients treated later in salvage (median of 42.0 vs. 35.8 months, P = 0.041), with no differences in toxicity, dose reductions, or discontinuations despite longer treatment. Therefore, lenalidomide plus dexamethasone is both effective and tolerable for second-line MM therapy and the data suggest that the greatest benefit occurs with earlier use. © 2009 Blackwell Munksgaard

European perspective on multiple myeloma treatment strategies in 2014

The treatment of multiple myeloma has undergone significant changes and has resulted in the achievement of molecular remissions, the prolongation of remission duration, and extended survival becoming realistic goals, with a cure being possible in a small but growing number of patients. In addition, nowadays it is possible to categorize patients more precisely into different risk groups, thus allowing the evaluation of therapies in different settings and enabling a better comparison of results across trials. Here, we review the evidence from clinical studies, which forms the basis for our recommendations for the management of patients with myeloma. Treatment approaches depend on "fitness," with chronological age still being an important discriminator for selecting therapy. In younger, fit patients, a short three drug-based induction treatment followed by autologous stem cell transplantation (ASCT) remains the preferred option. Consolidation and maintenance therapy are attractive strategies not yet approved by the European Medicines Agency, and a decision regarding post-ASCT therapy should only be made after detailed discussion of the pros and cons with the individual patient. Two- and three-drug combinations are recommended for patients not eligible for transplantation. Treatment should be administered for at least nine cycles, although different durations of initial therapy have only rarely been compared so far. Comorbidity and frailty should be thoroughly assessed in elderly patients, and treatment must be adapted to individual needs, carefully selecting appropriate drugs and doses. A substantial number of new drugs and novel drug classes in early clinical development have shown promising activity. Their introduction into clinical practice will most likely further improve treatment results

European perspective on multiple myeloma treatment strategies: Update following recent congresses

The management of multiple myeloma has undergone profound changes over the recent past as a result of advances in our understanding of the disease biology as well as improvements in treatment and supportive care strategies. Notably, recent years have seen a surge in studies incorporating the novel agents thalidomide, bortezomib, and lenalidomide into treatment for different disease stages and across different patient groups. This article presents an update to a previous review of European treatment practices and is based on discussions during an expert meeting that was convened to review novel agent data published or presented at medical meetings until the end of 2011 and to assess their impact on treatment strategies

Prevention and management of adverse events of novel agents in multiple myeloma: A consensus of the European Myeloma Network

During the last few years, several new drugs have been introduced for treatment of patients with multiple myeloma, which have significantly improved the treatment outcome. All of these novel substances differ at least in part in their mode of action from similar drugs of the same drug class, or are representatives of new drug classes, and as such present with very specific side effect profiles. In this review, we summarize these adverse events, provide information on their prevention, and give practical guidance for monitoring of patients and for management of adverse events. © 2018 The Author(s)

Bortezomib or high-dose dexamethasone for relapsed multiple myeloma

BACKGROUND: This study compared bortezomib with high-dose dexamethasone in patients with relapsed multiple myeloma who had received one to three previous therapies. METHODS: We randomly assigned 669 patients with relapsed myeloma to receive either an intravenous bolus of bortezomib (1.3 mg per square meter of body-surface area) on days 1, 4, 8, and 11 for eight three-week cycles, followed by treatment on days 1, 8, 15, and 22 for three five-week cycles, or high-dose dexamethasone (40 mg orally) on days 1 through 4, 9 through 12, and 17 through 20 for four five-week cycles, followed by treatment on days 1 through 4 for five four-week cycles. Patients who were assigned to receive dexamethasone were permitted to cross over to receive bortezomib in a companion study after disease progression. RESULTS: Patients treated with bortezomib had higher response rates, a longer time to progression (the primary end point), and a longer survival than patients treated with dexamethasone. The combined complete and partial response rates were 38 percent for bortezomib and 18 percent for dexamethasone (P<0.001), and the complete response rates were 6 percent and less than 1 percent, respectively (P<0.001). Median times to progression in the bortezomib and dexamethasone groups were 6.22 months (189 days) and 3.49 months (106 days), respectively (hazard ratio, 0.55; P<0.001). The one-year survival rate was 80 percent among patients taking bortezomib and 66 percent among patients taking dexamethasone (P=0.003), and the hazard ratio for overall survival with bortezomib was 0.57 (P=0.001). Grade 3 or 4 adverse events were reported in 75 percent of patients treated with bortezomib and in 60 percent of those treated with dexamethasone. CONCLUSIONS: Bortezomib is superior to high-dose dexamethasone for the treatment of patients with multiple myeloma who have had a relapse after one to three previous therapies. Copyrigh