Long-term Results of Response to Therapy, Time to Progression, and Survival With Lenalidomide Plus Dexamethasone in Newly Diagnosed Myeloma

Division of Hematology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.
Mayo Clinic Proceedings (Impact Factor: 6.26). 11/2007; 82(10):1179-84. DOI: 10.4065/82.10.1179
Source: PubMed


To determine the long-term effects of a combined regimen of lenalidomide and dexamethasone (Rev-Dex) on time to progression, progression-free survival, and overall survival (OS) in patients with multiple myeloma.
From March 2004 through October 2004, 34 patients were registered for the study. They were treated with 25 mg/d of lenalidomide on days 1 through 21 of a 28-day cycle and 40 mg/d of dexamethasone on days 1 through 4, 9 through 12, and 17 through 20 of each cycle. After 4 cycles of therapy, patients were allowed to discontinue treatment to pursue autologous stem cell transplant (SCT). Treatment beyond 4 cycles was permitted at the physician s discretion.
Thirteen patients proceeded to SCT after initial therapy and were censored at that time point for purposes of calculation of response. Thirty-one patients achieved an objective response, defined as a partial response or better (91%; 95% confidence interval, 79%-98%), with a complete response plus very good partial response rate of 56%. The complete response plus very good partial response among the 21 patients who received Rev-Dex without SCT was 67%. The 2-year progression-free survival rates for patients proceeding to SCT and patients remaining on Rev-Dex were 83% and 59%, respectively; the OS rates were 92% and 90% at 2 years and 92% and 85% at 3 years, respectively. The 3-year OS rate for the whole cohort was 88%.
The Rev-Dex regimen is highly active in the treatment of newly diagnosed multiple myeloma. Responses are durable with a low progression rate at 2 years. Randomized trials that incorporate quality-of-life measures are needed to determine if this and other combination regimens are better used early in therapy or should be reserved for later interventions.

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    • "Abbreviations: BiRD = biaxin (clarithromycin)/revlimid (lenalidomide)/dexamethasone; CBD = cyclophosphamide/bortezomib/dexamethasone; CNHT = cumulative main nonhematologic toxicity; CR = complete remission; CTD = cyclophosphamide/thalidomide/dexamethasone; DTPACE = dexamethasone/thalidomide/platinum/doxorubicin/cyclophosphamide/etoposide; Dvd-T = doxil/vincristine/low-dose dexamethasone; L = lenalidomide; MHT = maximal hematologic toxicity; MPT = melphalan/prednisone/thalidomide; MPR = melphalan/prednisone/lenalidomide; ORR = overall response rate; OS = overall survival; PAD = bortezomib/doxorubicin/dexamethasone; PFS = progression-free survival; PR = partial remission; RCd = lenalidomide/cyclophosphamide /low-dose dexamethasone; RD = lenalidomide/dexamethasone; T = thalidomide; TD = thalidomide/dexamethasone; T-VADoxil = thalidomide/vincristine/doxorubicin/dexamethasone/doxil; V = velcade; VBMCP = vincristine/BCNU/melphalan/cyclophosphamide; VCD-VTD = velcade/cyclophosphamide/dexamethasone–velcade/thalidomide/dexamethasone; VDCR = velcade/ dexamethasone/cylophosphamide/lenalidomide; VDD = velcade/doxil/dexamethasone; VMP = velcade/melphalan/prednisone; VMPT = velcade/melphalan/prednisone/thalidomide; VT = velcade/ thalidomide; VTP = velcade/thalidomide/prednisone Dingli et al, 2005 12 Jagannath et al, 2005 13 Cavo et al, 2005 14 Wu et al, 2006 15 Offidani et al, 2006 16 Hussein et al, 2006 17 Mateos et al, 2006 18 Macro et al, 2006 19 Barlogie et al, 2006 20 Lacy et al, 2007 21 Wang et al, 2007 22 Rosinol et al, 2007 23 Jakubowiak et al, 2007 24 Belch et al, 2007 25 Palumbo et al, 2007 26 Zonder et al, 2007 27 Zervas et al, 2007 28 Facon et al, 2007 29 Palumbo et al 2007 30 Popat et al, 2008 31 Popat et al, 2008 31 Reeder et al, 2008 32 Kumar et al, 2008 33 Bensinger, 2008 34 Kumar et al 2008 35 Rosignol et al, 2008 36 Rosignol et al, 2008 36 Rosignol et al, 2008 36 "
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    ABSTRACT: The introduction of new drugs such as thalidomide, lenalidomide, and bortezomib has led to novel treatment strategies and significantly improved the outcome of patients with multiple myeloma (MM). The enhanced knowledge of myeloma pathogenesis has allowed the identification of new therapeutic targets and many clinical trials are either planned or in progress to evaluate these more selective drugs in the near future. The results of these studies, however, will have to be compared with the results of existing novel therapies for the treatment of MM in order to define whether new protocols do not duplicate current new standards and constitute a real improvement. We reviewed the results of a series of phase I, II, III studies with thalidomide, lenalidomide, and bortezomib combinations for newly diagnosed MM in order to define a reasonable standard in terms of activity, efficacy, and toxicity and to have a potentially useful starting point for comparisons with future investigational trials. Three-drug regimens appear to double the complete remission (CR) rate (20%), though regimens containing 4 drugs triple the CR rate (30%), compared with those containing only 2 agents (10%). These improvements in the depth and quality of response translate into a progressive increase in the progression-free survival rate at 2 years (from approximately 54%-62% to 75%, respectively). Conversely, by using additional agents, a marked increase in hematologic toxicity has been described (8%, 28%, and 28% respectively), whereas nonhematologic toxicity appears to be similar (26%, 24%, and 27%, respectively). These results suggest that new trials in the future will constitute significant progress if they can improve on the current relatively favorable efficacy/toxicity ratio. Nonetheless, exciting new combinations in development do hold promise and results from these studies are eagerly awaited.
    Full-text · Article · Oct 2010 · Clinical lymphoma, myeloma & leukemia
    • "Various regimens have been tried with a variable degree of success.[351314] Recently, the combination of lenalidomide with bortezomib and dexamethasone has shown to be very active in newly diagnosed, refractory and relapsed cases of MM patients, with high response rates and manageable toxicity.[1415] Although use of this regimen in PPCL has not been documented, we used this combination and the patient attained CR. "
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    ABSTRACT: Primary plasma cell leukemia is a rare form of plasma cell dyscrasia. We present a case which had leukocytosis with numerous circulating plasma cells in the peripheral blood. Flow cytometry revealed an unusual CD117 expression. Free light chain analysis in the serum showed a markedly elevated level of free lambda light chains. Radiography did not reveal any lytic lesions. Fluorescent in-situ hybridization analysis revealed deletion of 13q14.3 and t(4;14)/t(11;14), while the cytogenetic analysis was normal. The patient was given chemotherapy and was subjected to autologous stem cell transplant, after which she is in complete remission till date.
    No preview · Article · Jul 2010 · Indian journal of medical and paediatric oncology
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    • "TD has demonstrated superior response rates versus dexamethasone (63% vs 46%, P < 0AE001) and longer time-to-progression (median 22AE6 vs. 6AE5 months, P < 0AE001) (Rajkumar et al, 2008). Lenalidomide plus dexamethasone (RD) is also an effective induction therapy; ORR was 91%, with 18% CR/nCR and 56% ‡VGPR; with a median follow-up of 36 months, 3-year survival was 88% (Lacy et al, 2007). "
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    ABSTRACT: Novel sequential combination therapy for induction may improve the quality of response and therefore prolong survival in newly diagnosed multiple myeloma (MM) patients. We report results from a phase 2 study of two sequential three-drug combinations. Forty-four previously untreated, symptomatic MM patients received: bortezomib 1.3 mg/m(2) (days 1, 4, 8, 11), cyclophosphamide 300 mg/m(2) (days 1, 8), plus dexamethasone 40 mg (day of and day after bortezomib) for three 21-day cycles, followed by bortezomib 1.0 mg/m(2), dexamethasone 40 mg and thalidomide 100 mg daily for three cycles. Overall response rate for 42 evaluable patients was 95%, including 19% stringent complete response (sCR), 26% CR, and 57%>/= very good partial response. Twenty-two patients have undergone stem-cell transplantation. After a median follow-up of 20.9 months, five patients have died; none was induction therapy-related. Median event-free survival (EFS) and overall survival (OS) have not been reached; estimated 1-year EFS and OS rates were 81% and 91% respectively. Both three-drug combinations were well tolerated; 82% of patients completed all six cycles. Toxicities were predictable and manageable; the most-commonly reported grade 3/4 toxicity was neuropathy (11%). This novel sequential three-drug combination therapy is effective and well-tolerated in previously untreated MM patients.
    Full-text · Article · Nov 2009 · British Journal of Haematology
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