Celgene provided the lenalidomide and placebo used in this trial. Palumbo A, Hajek R, Delforge M, et al.

Additional eligibility criteria included a serum aspartate aminotransferase or alanine aminotransferase level that was no more than three times the upper limit of the normal range, a serum bilirubin level that was no more than 35 μmol per liter (2 mg per deciliter), a serum creatinine level of less than 160 μmol per liter (1.8 mg per deciliter), an absolute neutrophil count of at least 1000 per cubic millimeter, and a platelet count of more than 75,000 per cubic millimeter. Treatment was continued until the patient withdrew consent, the disease progressed, or unacceptable toxic effects occurred. Furthermore, the rate of febrile neutropenia was similar in the two study groups. Like Whitman, if you are going for a stem cell transplant for myeloma treatment, you will receive plenty of detailed information from your transplant center.

Standard chemotherapy compared with high-dose chemoradiotherapy for multiple myeloma: final results of phase III US Intergroup Trial S9321. Efficacy analyses were performed according to the intention-to-treat principle. A comparison of responses before and after consolidation was performed with the use of McNemar's test. ), Centre Hospitalier Brabois, Nancy (C.H.

DOI: 10.1056/NEJMoa1114138, Tap into groundbreaking research and clinically relevant insights. All patients stopped receiving lenalidomide maintenance therapy. Lenalidomide after stem-cell transplantation for multiple myeloma. Rajkumar SV, Hayman SR, Lacy MQ, et al. Randomization was stratified according to baseline levels of serum β2-microglobulin (≤3 mg per liter or >3 mg per liter), the presence or absence of a 13q deletion on the basis of fluorescence in situ hybridization, and response after transplantation achieved at the time of randomization (a complete or very good partial response vs. a partial response or stable disease). Marriott JB, Clarke IA, Dredge K, Muller G, Stirling D, Dalgleish AG. Studies have found out that the long-term outcome from tandem transplant is more compared to the usual autologous transplant and this outcome is much more if the patient is given a high dose of chemotherapy. Dr. Muzaffar Qazilbash and others reviewed the outcomes in patients with this deletion after they had received an autologous stem cell transplant. The median relative dose intensity of the study drug (the administered dose divided by the target dose) was 83% in the lenalidomide group and 94% in the placebo group. N Engl J Med 2007;357:2133-2142, 16. Blood and 24-hour urine samples were collected every 4 weeks from the time of randomization until disease progression. (Funded by the Programme Hospitalier de Recherche Clinique and others; ClinicalTrials.gov number, NCT00430365. Table 1 shows the baseline characteristics of the patients. Similar trials of lenalidomide maintenance have confirmed this risk.19,20 Second primary cancers (especially acute myeloblastic leukemia or the myelodysplastic syndrome) are part of the natural history of myeloma and its treatment.21 In our study, there were seven cases of acute lymphoblastic leukemia or Hodgkin's disease among patients who had received induction therapy with dexamethasone, cyclophosphamide, etoposide, and cisplatin or had undergone two transplantations and had received lenalidomide maintenance therapy for at least 2 years. Kaplan–Meier Curves for Progression-free Survival and Overall Survival in the Intention-to-Treat Population, According to Study Group, at Study Unblinding (July 2010). The content of this site is intended for health care professionals. The independent data and safety monitoring committee recommended stopping lenalidomide maintenance therapy and continuing follow-up each month to determine survival and detect second primary cancers. Sybil Whitman remembers traveling from her home in New Brunswick, Canada, to a hospital in Ottawa for her autologous myeloma stem cell transplant. In the multivariate analysis, the incidence of second primary cancers was significantly related to study-group assignment, age, sex, and International Staging System stage (Table 1 in the Supplementary Appendix). ), Hôpital Haut-Lévêque, Bordeaux Pessac (G.M. Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Tandem Transplant– This is having 2 autologous transplants in 6-12 months apart with medication/chemotherapy in between the transplants. Lenalidomide maintenance therapy improved the rate of a complete or very good partial response, as compared with placebo (P=0.009) (Table 2). Child JA, Morgan GJ, Davies FE, et al. A recent Mayo Clinic study of more than 700 autologous stem cell transplants for multiple myeloma found that nearly 40 percent were performed on an outpatient basis. After a median follow-up of 45 months from the time of randomization (and 55 months from the time of diagnosis), overall survival was similar in the two study groups. An increased risk of acute lymphoblastic leukemia or Hodgkin's disease has not previously been reported among patients with myeloma.21 Currently, the beneficial effect of lenalidomide maintenance therapy on event-free survival suggests that more patients receive benefit than are harmed; however, the risk of second primary cancers is serious, and longer follow-up periods will be necessary to accurately quantify the risk. Get To Know What Possibly Could Be Causing Your Symptoms! Weber DM, Chen C, Niesvizky R, et al. N Engl J Med 2012;366:1770-1781, 20. ), During the past decade, high-dose chemotherapy with autologous stem-cell transplantation has become the standard treatment for newly diagnosed myeloma in patients younger than 65 years of age. The role of maintenance thalidomide therapy in multiple myeloma: MRC myeloma IX results and meta-analysis. It is shown that the death rate after 100 days of allogeneic transplant range from 10-56%.eval(ez_write_tag([[250,250],'epainassist_com-large-leaderboard-2','ezslot_11',151,'0','0'])); Another retrospective case study shows that the median survival rate after autologous transplant is about 34 months whereas after allogeneic transplant it is about 18 months.(2). The widespread use of high-dose therapy and autologous stem cell transplantation (ASCT) as well as the introduction of novel agents have significantly improved outcomes in multiple myeloma (MM) enabling long-term survival. 18.

A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma. Thromboprophylaxis was not used. ); and Cliniques Universitaires Saint-Luc, Catholic University of Louvain, Brussels (M.C.-V.). However, this transplant is not considered now as many patients had a poor short-term outcome.

All authors had full access to the primary data and results of the final analysis, made the decision to submit the manuscript for publication, and vouch for the accuracy and completeness of the data and analyses. These cells are harvested from the blood and stored appropriately to use in the future.

Celgene donated the drug and the placebo but played no other role in the study. "They contain detailed descriptions of the procedures, the drug protocols, all the possible side effects, and what to do about them. Median event-free survival (with events that included second primary cancers) was significantly improved with lenalidomide (40 months, vs. 23 months with placebo; P<0.001). However, these toxic effects were manageable with dose adjustment, without the need for granulocyte colony-stimulating factors or prophylactic antibiotics.

1 in the Supplementary Appendix). However, the median duration of response after this procedure does not exceed 3 years, and few patients remain free of the disease for more than 10 years.1-4.
Panel B shows overall survival. An increased incidence rate of second primary cancers was observed in the lenalidomide group. Do You Lose Weight With Multiple Myeloma? As of October 2011, a total of 124 patients in the lenalidomide group had disease progression, and 108 symptomatic patients had received a second-line therapy: lenalidomide (in 16 patients), bortezomib (in 54), thalidomide (in 5), bortezomib plus thalidomide (in 10), or chemotherapy without new agents (in 23). The chemotherapy dose and a number of transplants should be decided according to the individual patient and this decision will be taken by the team involved with the patient’s treatment. Relapses are due to the failure of high-dose chemotherapy to eradicate all myeloma cells. ), Hôpital St.-Antoine (L.G.) N Engl J Med 2007;357:2123-2132[Erratum, N Engl J Med 2009;361:544. Blood 2012;119:7-15, 12. Because stem cell transplant is a core myeloma therapy, they studied the impact of stem cell transplant on patients with the TP53 deletion.

As of October 2011, an increased incidence of second primary cancers was observed in the lenalidomide group (Table 4, and Fig. Studies have shown that the response rate, relapse-free survival, and event-free survival rates are high with tandem transplant. Baseline Characteristics of the Patients. Although thromboembolic events were less frequent in our patients who received lenalidomide maintenance than in patients who received lenalidomide plus dexamethasone for newly diagnosed or relapsed refractory disease,14,15 our experience justifies the use of prophylactic antithrombotic therapy in future lenalidomide maintenance studies. Thromboembolic complications were reported more frequently in the lenalidomide group than in the placebo group (6% vs. 2%, P=0.01). N Engl J Med 2003;348:1875-1883, 3. In January 2011, an increased incidence of second primary cancers was observed in the lenalidomide group. Then, after high-dose chemotherapy, the stem cells are put back into your body to replace the myeloma cells. The overall survival rate 4 years after randomization was similar in the two groups (73% in the lenalidomide group and 75% in the placebo group) (Fig. This is a standard treatment for multiple myeloma patients and most of the time the myeloma goes away but it comes back after a few years. The authorized source of trusted medical research and education for the Chinese-language medical community. Durie BG, Harousseau JL, Miguel JS, et al.

The adverse events reported in the lenalidomide group were consistent with established toxicity profiles of lenalidomide.14,15 The most frequent adverse events were hematologic. The study was a randomized, double-blind, placebo-controlled, phase 3 trial conducted at 77 centers in France, Belgium, and Switzerland. A note on quantifying follow-up in studies of failure time.

The rate of grade 3 or 4 peripheral neuropathy was low in both study groups (about 1%). McCarthy PL, Owzar K, Hofmeister CC, et al. Six patients (1 in the lenalidomide group and 5 in the placebo group) did not receive the assigned study drug.