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Relapsed/refractory MM (refractory + mm)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Thalidomide for the Treatment of Refractory Multiple Myeloma: Association of Plasma Concentrations of Thalidomide and Angiogenic Growth Factors with Clinical Outcome

CANCER SCIENCE, Issue 9 2002
Tsunayuki Kakimoto
Recent reports showed that thalidomide has anti-angiogenic activity and is effective for the treatment of refractory multiple myeloma (MM). We examined the relationship between the clinical efficacy and adverse effects of thalidomide and the plasma concentrations of this drug as well as angiogenic growth factors in refractory MM. Ten out of twenty-four evaluable patients (42%) showed more than 25% reduction of M-protein, and eight (33%) achieved more than 50% reduction. These changes were associated with restoration of anemia and recovery of normal immunoglobulin level. Somnolence and headache, constipation, peripheral neuropathy and skin rash were frequently observed, but were well tolerated. However, grade 2,4 severe neutropenia was also observed in nine cases. These adverse effects other than neutropenia occurred more frequently in the patients with higher plasma concentrations of thalidomide (,2.0 ,g/ml at 12 h after the last administration) and were readily alleviated by dose reduction. In contrast, neutropenia developed regardless of the plasma concentration. Plasma concentrations of angiogenic growth factors were frequently elevated before treatment. After thalidomide treatment, these growth factor levels tend to decrease to near-normal ranges in responders but were still high in most non-responders. After thalidomide treatment, plasma vascular endothelial growth factor (VEGF) level was significantly reduced in responders (P=0.025), but not in non-responders (P=0.37). Reduction of plasma VEGF level might be an important indicator for anti-myeloma effect of thalidomide. [source]

Lenalidomide and dexamethasone for the treatment of refractory/relapsed multiple myeloma: dosing of lenalidomide according to renal function and effect on renal impairment

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2010
Meletios A. Dimopoulos
Abstract Objectives:, Lenalidomide and dexamethasone (LenDex) is an active regimen for relapsed/refractory multiple myeloma (MM). However, there is limited data for the effect of LenDex on renal impairment (RI) and on renal reversibility. Patients & Methods:, Fifty consecutive patients with relapsed/refractory MM received LenDex in 28-d cycles. Median lines of previous therapies were 2 (range: 1,6). Lenalidomide was administered on days 1,21 according to creatinine clearance (CrCl), while dexamethasone was given at a dose of 40 mg on days 1,4 and 15,18 for the first four cycles and only on days 1,4 thereafter. Results:, Twelve patients (24%) had RI at baseline, defined as CrCl < 50 mL/min. Most patients were pretreated with either thalidomide or bortezomib and > 50% of them were refractory to both drugs. At least partial response was documented in 60.5% and 58% of patients with and without RI. Median progression-free survival (PFS) and overall survival (OS) for all patients was 9 and 16 months, respectively. RI was not associated with an inferior PFS or OS. There were no differences in the incidence of adverse events among patients with and without RI. Three of 12 patients with RI (25%) achieved complete renal response and two (16%) achieved minor renal response with LenDex. Conclusions:, We conclude that LenDex is an active treatment even in heavily pretreated MM. With dosing of lenalidomide according to renal function, LenDex can be administered to patients with RI (who may not have other treatment options) without excessive toxicity. Furthermore, LenDex may improve the renal function in approximately 40% of patients with RI. [source]

A systematic review of phase II trials of thalidomide/dexamethasone combination therapy in patients with relapsed or refractory multiple myeloma

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2008
Marie Von Lilienfeld-Toal
Abstract Thalidomide monotherapy in relapsed/refractory multiple myeloma (MM) has a response rate of 30%. The combination of thalidomide with dexamethasone (Thal/Dex) is expected to improve responses, but it is unknown if the combination increases the rate of adverse events. Here, we conducted a systematic review of studies evaluating Thal/Dex in relapsed/refractory MM. Twelve studies were included, comprising 451 patients. The response rate (CR and PR) was 46% (95% CI 42,51%). Therapy-related toxicity was comparable to thalidomide monotherapy and included somnolence (26%, 95% CI 22,31%), constipation (37%, 95% CI 32,42%) and peripheral neuropathy (27%, 95% CI 23,32%). Only venous thromboembolism appeared to occur more often with Thal/Dex (5%, 95% CI 3,8%). Thus, using Thal/Dex results in an improved response rate in relapsed/refractory MM, with a toxicity rate comparable to thalidomide monotherapy. [source]

Non-myeloablative conditioning and allogeneic transplantation for multiple myeloma,

AMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2010
Keren Osman
In multiple myeloma (MM), allogeneic stem cell transplantation (alloHCT) carries a lower relapse risk than autologous transplantation but a greater transplant-related mortality. Nonmyeloablative conditioning for allogeneic transplantation (NST) reduces transplant-related toxicity. Results are encouraging when used during first remission in low-risk patients, but less-so in relapsed or refractory disease. This is a single-center retrospective analysis of 20 previously treated MM patients who underwent NST from matched-related or matched-unrelated donors from 2000,2006. Median age was 52.7 years (37.2,68.0). Twenty-five percent had advanced or high-risk disease. Eleven still had active disease prior to NST. Conditioning was total body irradiation 200 cGy on a single fraction on day ,5, followed by antithymocyte globulin (ATG) 1.5 mg/kg/day and fludarabine 30 mg/m2/day on days ,4 to ,2. All received immunosuppression, most commonly with oral mycofenylate mofetil and cyclosporine beginning on day ,5. At day 100, 50% had achieved complete remission. Transplant-related mortality was 25%. Median overall survival (OS) was 21.2 months (0.6,90+) and progression-free survival (PFS) 6.6 months (0.6,90+). Both OS and PFS were 24% at 3 years. OS was significantly greater for patients with age <52 years (median 27 months vs. 7.9 months, P = 0.031), and there was a trend toward greater OS for those with ,2 microglobulin <2.5 mg/l (median 27 months vs. 7.7 months, P = 0.08). Donor characteristics and Ig type had no significant effect on survival. These data suggest a benefit of NST in relapsed/refractory MM. Randomized trials must be performed to confirm and further qualify this benefit. Am. J. Hematol., 2010. © 2010 Wiley-Liss, Inc. [source]