Outcomes of maintenance therapy with lenalidomide or bortezomib in multiple myeloma in the setting of early autologous stem cell transplantation

Leukemia ◽  
2017 ◽  
Vol 32 (3) ◽  
pp. 712-718 ◽  
Author(s):  
R Chakraborty ◽  
E Muchtar ◽  
S K Kumar ◽  
F K Buadi ◽  
D Dingli ◽  
...  
2019 ◽  
Vol 19 (10) ◽  
pp. 889-898 ◽  
Author(s):  
Almuth Maria Anni Merz ◽  
Maximilian Merz ◽  
Jens Hillengass ◽  
Sarah A. Holstein ◽  
Philip McCarthy

2017 ◽  
Vol 23 (2) ◽  
pp. 262-268 ◽  
Author(s):  
Dharshan Sivaraj ◽  
Michael M. Green ◽  
Zhiguo Li ◽  
Anthony D. Sung ◽  
Stefanie Sarantopoulos ◽  
...  

Blood ◽  
2012 ◽  
Vol 119 (13) ◽  
pp. 3003-3015 ◽  
Author(s):  
Heinz Ludwig ◽  
Brian G. M. Durie ◽  
Philip McCarthy ◽  
Antonio Palumbo ◽  
Jésus San Miguel ◽  
...  

Abstract Maintaining results of successful induction therapy is an important goal in multiple myeloma. Here, members of the International Myeloma Working Group review the relevant data. Thalidomide maintenance therapy after autologous stem cell transplantation improved the quality of response and increased progression-free survival (PFS) significantly in all 6 studies and overall survival (OS) in 3 of them. In elderly patients, 2 trials showed a significant prolongation of PFS, but no improvement in OS. A meta-analysis revealed a significant risk reduction for PFS/event-free survival and death. The role of thalidomide maintenance after melphalan, prednisone, and thalidomide is not well established. Two trials with lenalidomide maintenance treatment after autologous stem cell transplantation and one study after conventional melphalan, prednisone, and lenalidomide induction therapy showed a significant risk reduction for PFS and an increase in OS in one of the transplant trials. Maintenance therapy with single-agent bortezomib or in combination with thalidomide or prednisone has been studied. One trial revealed a significantly increased OS with a bortezomib-based induction and bortezomib maintenance therapy compared with conventional induction and thalidomide maintenance treatment. Maintenance treatment can be associated with significant side effects, and none of the drugs evaluated is approved for maintenance therapy. Treatment decisions for individual patients must balance potential benefits and risks carefully, as a widely agreed-on standard is not established.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5373-5373
Author(s):  
Michael T. Byrne ◽  
Jan S Moreb

Background In spite of recent improvements in survival, multiple myeloma (MM) remains an incurable disease.  Following autologous stem cell transplantation (ASCT), maintenance therapy has been shown to improve progression free survival (PFS) but data on overall survival (OS) is mixed.  The expense of therapy is significant and a substantial number of patients are unable to tolerate its toxicity.  In this study, we report our experience with the use of oral cyclophosphamide ± prednisone (CY) as an alternative for these patients.  Methods From January of 2000 to December of 2010, we retrospectively evaluated all patients with MM who underwent ASCT at our institution and separated them into four groups depending on maintenance therapy: No maintenance, interferon ± prednisone (IFN/Pd), IMIDs, and CY.  Patients who received maintenance after their first relapse were analyzed separately for tolerability, PFS, and OS.  Survival data was analyzed by logrank test and the group characteristics were compared using an unpaired t-test.    Results A total of 288 patients underwent ASCT at our institution from 2000 to 2010.  Of these patients, 8 were excluded due to insufficient follow-up.  1 patient who received bortezomib was also excluded. The median age at diagnosis was 58.0 years and the median time from diagnosis to ASCT was 8.3 months.  Collectively, this cohort included 193 Caucasians, 64 African Americans, 16 Hispanics, 4 Asian and 2 unknown race; 55.7% were men and 44.3% were women.  Following ASCT, 112 patients received no maintenance therapy, 74 of them (66.1%) had documented relapses with a median PFS of 18.2 months.  78 patients received IFN/Pd; 55 of them (70.5%) relapsed with a median PFS of 18.4 months. Alternatively, 79 patients were treated with IMIDs with 40 known relapses (50.6%) and a median PFS of 22.5 months.   CY maintenance was used in 10 patients; six patients relapsed within a median time of 20.4 months.  Collectively, maintenance therapy was associated with a significant improvement in PFS (22.5 vs. 18.2 months, p=0.037) but no difference in OS (45.5 vs. 43.9 months, p=0.29).  Among patients treated with maintenance therapy, PFS was superior in the group treated with IMIDs compared to IFN/Pd (22.5 vs. 18.4 months, p <0.001) however there was no improvement in OS (43.1 vs. 46.5 months, p=0.29). PFS was equivocal between CY and all other maintenance (20.4 vs. 22.5 months, p=0.19).  OS of first-remission CY vs. other maintenance therapy cannot be calculated due to small sample size.  34.6-38.8% of patients who received non-CY maintenance therapy had toxicity requiring dose reductions or discontinuation whereas 10% of CY patients developed toxicity (Table 1).  Following relapse and salvage therapy, 78 patients received non-CY second-remission maintenance therapy with a median PFS of 9.2 months whereas those treated with second-remission CY (n=25) had a median PFS of 11.7 months (p=0.89).  OS was comparable between the two groups (69.2 vs. 79.8 months, p=0.44).  Patients who received CY, however, had a significantly longer OS compared to those who did not receive second-remission maintenance therapy (79.8 vs. 41.2 months, p<0.001) and a trend toward improved OS compared to other forms of second remission maintenance (p=0.085).  5.0% of patients in this study developed secondary malignancies: 4 in non-maintenance group, 3 in the IFN/Pd group, 6 in the IMID group, and 1 in the CY group (Table 2).  Conclusions  CY is well tolerated with comparable efficacy to other maintenance drugs in MM, particularly in the second maintenance setting. Our data corroborates published experience that maintenance therapy improves PFS but often fails to impact OS.  Such improvement in PFS with conventional maintenance therapy is associated with a high rate of toxicity and an increase in secondary malignancies. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2008 ◽  
Vol 111 (4) ◽  
pp. 1805-1810 ◽  
Author(s):  
Abderrahman Abdelkefi ◽  
Saloua Ladeb ◽  
Lamia Torjman ◽  
Tarek Ben Othman ◽  
Amel Lakhal ◽  
...  

From April 2003 to December 2006, 195 patients with de novo symptomatic myeloma and younger than 60 years of age were randomly assigned to receive either tandem transplantation up front (arm A, n = 97) or one autologous stem-cell transplantation followed by a maintenance therapy with thalidomide (day + 90, 100 mg per day during 6 months) (arm B, n = 98). Patients included in arm B received a second transplant at disease progression. In both arms, autologous stem-cell transplantation was preceded by first-line therapy with thalidomide-dexamethasone and subsequent collection of peripheral blood stem cells with high-dose cyclophosphamide (4 g/m2) and granulocyte colony stimulating factor. Data were analyzed on an intent-to-treat basis. With a median follow-up of 33 months (range, 6–46 months), the 3-year overall survival was 65% in arm A and 85% in arm B (P = .04). The 3-year progression-free survival was 57% in arm A and 85% in arm B (P = .02). Up-front single autologous transplantation followed by 6 months of maintenance therapy with thalidomide (with second transplant in reserve for relapse or progression) is an effective therapeutic strategy to treat multiple myeloma patients and appears superior to tandem transplant in this setting. This study was registered at www.ClinicalTrials.gov as (NCT 00207805).


Hematology ◽  
2011 ◽  
Vol 2011 (1) ◽  
pp. 205-207 ◽  
Author(s):  
Emma Scott ◽  
Donna Reece

Abstract An otherwise healthy 60-year-old male was diagnosed with stage II multiple myeloma by the International Staging System characterized by anemia, diffuse lytic bone lesions, IgG kappa paraproteinemia, 45% bone marrow plasmacytosis and the t(4;14) by FISH and conventional cytogenetics. The patient had a very good partial remission with initial induction therapy consisting of four 3-week cycles of bortezomib 1.3 mg/m2 IV on days 1, 4, 8, and 11 plus dexamethasone 40 mg days 1-4 (all cycles), followed by a cyclophosphamide and G-CSF mobilized melphalan 200 mg/m2 autologous stem cell transplantation (ASCT) and experienced minimal side effects. He is doing well 60 days post-ASCT and is in a near complete remission. His oncologist recommends maintenance therapy with lenalidomide or bortezomib, but the patient is concerned about the increased risk of developing a secondary malignancy (SM), and because he has had such an encouraging response to induction therapy, he wonders if he could remain off therapy.


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