scholarly journals Maintenance therapy in multiple myeloma

2016 ◽  
Vol 8 (2) ◽  
pp. 71-79 ◽  
Author(s):  
Prerna Mewawalla ◽  
Abhishek Chilkulwar

Despite recent advances, multiple myeloma remains an incurable disease. Induction therapy followed by autologous transplantation has become the standard of care. The idea of maintenance therapy in multiple myeloma is not new. Starting with chemotherapy in 1975, to interferon in 1998, to novel agents recently, a multitude of agents have been explored in patients with multiple myeloma. In spite of the novel agents, multiple myeloma continues to be an incurable disease with the progression-free survival after autologous transplant rarely exceeding 3 years. The goal of using maintenance therapy has been to improve the outcomes following autologous transplantation by increasing the progression-free survival, deepening remissions and perhaps increasing overall survival. It has been shown that patients with a stringent complete response (CR) have a better outcome [Kapoor et al. 2013]. It is becoming increasingly common to check minimal residual disease (MRD) as a means of assessing depth of response. It has also been shown that patients with no MRD have not only a better progression-free survival but also a better overall survival compared with patients who are MRD positive. This makes it even more important to find agents for maintenance therapy, which can further deepen and maintain responses. Here, we present a comprehensive review of the agents studied as maintenance for multiple myeloma and their efficacy, both in terms of overall survival, progression-free survival and toxicity.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2759-2759
Author(s):  
Sabine Gerull ◽  
Ute Hegenbart ◽  
Martin Goerner ◽  
Axel Benner ◽  
Thomas Moehler ◽  
...  

Abstract Patients with recurrent and refractory multiple myeloma have a very limited survival expectance. Allogeneic transplantation might offer an option for cure in myeloma and the recent development of non-myeloablative conditioning regimens has reduced transplant related morbidity and mortality and rendered this treatment feasible in elderly patients. The role of non-myeloablative allogeneic transplantation for multiple myeloma however, has not yet been defined. We have analyzed the results of patients with relapsed or refractory multiple myeloma treated at our institution. Between 08/1999 and 02/2004, 56 patients with relapsed (n=54) or refractory (n=2) myeloma were treated with non-myeloablative allogeneic transplantation. The median beta2microglobulin at the time of diagnosis was 2.75 mg/l, and median age at the time of transplant was 54.5 years (39.2–67.8). The median time from diagnosis to transplant was 3.6 years. Prior to allogeneic transplantation, patients received reinduction chemotherapy which included an autologous transplantation for 30 patients. The median number of previous cycles of conventional chemotherapy was 9. The conditioning regimen was 2 Gy TBI with (n=43) or without (n=3) fludarabin 3 x 30 mg/m² for 46 patients, the remaining 10 patients received a melphalan containing regimen. Acute toxicity was low with a WBC < 500/μl and platelets < 50/μl for a median of 0 days. Engraftment was prompt with 90 % of patients having achieved > 90 % donor chimerism by day 56. Acute GvHD Grade II-IV occurred in 36 % of patients with 22 % Grade III-IV, and 61 % experienced chronic GvHD. Total transplant related mortality reached 20 %, with a day 100 TRM of 5 %. 32 patients experienced relapse or progressive disease, and 32 % of patients died due to relapse. The Kaplan-Meier estimate of overall survival and progression free survival at 18 months was 40 % and 25 %, respectively, with a median follow up of survivors of 21 months. Patients who experienced cGvHD had a significantly higher overall survival estimate (60 % vs. 20 % at 18 months, p=0.03). The number of cycles of pretreatment before allogeneic transplantation had a statistically significant negative influence on overall (p=0.02) and progression free survival (p=0.006). We conclude that non-myeloablative allogeneic transplantation is feasible in patients with relapsed multiple myeloma. The significant poor prognostic factors we identified were absence of chronic GvHD and number of cycles of pretreatment. Allogeneic transplantion should therefore be considered as an option earlier in the course of the disease.


2014 ◽  
Vol 32 (7) ◽  
pp. 634-640 ◽  
Author(s):  
Antonio Palumbo ◽  
Sara Bringhen ◽  
Alessandra Larocca ◽  
Davide Rossi ◽  
Francesco Di Raimondo ◽  
...  

Purpose Bortezomib-melphalan-prednisone (VMP) has improved overall survival in multiple myeloma. This randomized trial compared VMP plus thalidomide (VMPT) induction followed by bortezomib-thalidomide maintenance (VMPT-VT) with VMP in patients with newly diagnosed multiple myeloma. Patients and Methods We randomly assigned 511 patients who were not eligible for transplantation to receive VMPT-VT (nine 5-week cycles of VMPT followed by 2 years of VT maintenance) or VMP (nine 5-week cycles without maintenance). Results In the initial analysis with a median follow-up of 23 months, VMPT-VT improved complete response rate from 24% to 38% and 3-year progression-free-survival (PFS) from 41% to 56% compared with VMP. In this analysis, median follow-up was 54 months. The median PFS was significantly longer with VMPT-VT (35.3 months) than with VMP (24.8 months; hazard ratio [HR], 0.58; P < .001). The time to next therapy was 46.6 months in the VMPT-VT group and 27.8 months in the VMP group (HR, 0.52; P < .001). The 5-year overall survival (OS) was greater with VMPT-VT (61%) than with VMP (51%; HR, 0.70; P = .01). Survival from relapse was identical in both groups (HR, 0.92; P = .63). In the VMPT-VT group, the most frequent grade 3 to 4 adverse events included neutropenia (38%), thrombocytopenia (22%), peripheral neuropathy (11%), and cardiologic events (11%). All of these, except for thrombocytopenia, were significantly more frequent in the VMPT-VT patients. Conclusion Bortezomib and thalidomide significantly improved OS in multiple myeloma patients not eligible for transplantation.


2021 ◽  
Vol 12 ◽  
pp. 204062072110303
Author(s):  
Cheong Ngai ◽  
Shaji Kumar ◽  
Garrett Chi-lai Ho ◽  
Sirong Chen ◽  
Chor-sang Chim

Complete response (CR) is an important favorable factor for survival in multiple myeloma (MM). However, CR patients continue to relapse, especially in the presence of minimal residual disease (MRD). Bone marrow (BM) MRD is predictive of progression-free survival (PFS) in MM. However, myeloma outside the BM aspiration site may result in subsequent relapse despite MRD-negativity. Therefore, positron emission tomography-computed tomography (PET-CT) based on F-fluorodeoxyglucose (FDG) is a complementary tool to monitor residual disease in MM. However, FDG may miss myeloma lesions that are not FDG-avid. On the other hand, 11C-Acetate (ACT) has been found to be a more sensitive and specific tracer than FDG in MM. Recently, the addition of daratumumab to bortezomib, thalidomide, dexamethasone (VTd) or bortezomib, lenalidomide, dexamethasone (VRd) backbone has been proven to improve outcomes. Herein, we report three newly-diagnosed MM patients achieving deep responses with imaging CR using ACT PET in addition to conventional immunofixation CR and MRD-negative CR after a 3-weekly daratumumab-based quadruplet induction regimen.


Blood ◽  
2012 ◽  
Vol 120 (13) ◽  
pp. 2581-2588 ◽  
Author(s):  
María-Victoria Mateos ◽  
Albert Oriol ◽  
Joaquín Martínez-López ◽  
Norma Gutiérrez ◽  
Ana-Isabel Teruel ◽  
...  

Abstract Maintenance therapy has become a hot field in myeloma, and it may be particularly relevant in elderly patients because the major benefit results from the initial therapy. We report the results of a randomized comparison of maintenance with bortezomib plus thalidomide (VT) or prednisone (VP) in 178 elderly untreated myeloma patients who had received 6 induction cycles with bortezomib plus either melphalan and prednisone or thalidomide and prednisone. The complete response (CR) rate increased from 24% after induction up to 42%, higher for VT versus VP (46% vs 39%). Median progression-free survival (PFS) was superior for VT (39 months) compared with VP (32 months) and overall survival (OS) was also longer in VT patients compared with VP (5-year OS of 69% and 50%, respectively) but the differences did not reach statistical significance. CR achievement was associated with a significantly longer PFS (P < .001) and 5-year OS (P < .001). The incidence of G3-4 peripheral neuropathy was 9% for VT and 3% for VP. Unfortunately, this approach was not able to overcome the adverse prognosis of cytogenetic abnormalities. In summary, these maintenance regimens result in a significant increase in CR rate, remarkably long PFS, and acceptable toxicity profile. The trial is registered at www.clinicaltrials.gov as NCT00443235.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1343-1343
Author(s):  
Joyce Habib ◽  
Neil Dunavin ◽  
Gary Phillips ◽  
Patrick Elder ◽  
Meaghan Tranovich ◽  
...  

Abstract Abstract 1343 Background: Multiple myeloma (MM) is the second most common hematological malignancy in the United States with an estimated 20,580 new cases in 2009. Over the past decade, the introduction of novel agents (thalidomide, lenalidomide and bortezomib) have played a pivotal role in improving response rates, duration of response, overall survival (OS) and quality of life. In this study we describe a single center experience with novel agents used for induction followed by high dose chemotherapy (HDT) and first autologous stem cell transplant (ASCT) in patients with MM. Method: A retrospective review of the medical records of 179 newly diagnosed patients with MM seen between October 2006 and December 2009 at The Ohio State University was performed. All patients received novel therapy containing thalidomide, bortezomib or lenalidomide as part of an induction regimen followed by ASCT. All patients received melphalan 140mg/m2 or 200mg/m2 as preparative regimen. Kaplan-Meier estimates were used to plot progression free survival and overall survival. Results: Of the 181 patients seen, 2 were excluded because they did not receive a novel agent as part of induction treatment. Of the 179 patients analyzed, median age was 56.8 years (29-80) with 30% of patients older than 60 years. African American represented 19%. Fifty-nine percent were male, 80% had Durie-Salmon (DS) stage III while 25%, 28%, 18% represented International prognostic score (IPS) stage I, II, and III respectively with 27% unknown. Median comorbidity index score was 2 (2-7) and median Karnofsky performance score (KPS) was 90% (70-100). Thirty percent had high risk genetic profile, and 73% received one line of treatment before ASCT. The median time from diagnosis to ASCT was 8.33 months (4-58). The overall response rate (ORR) prior to transplant was 84% (9% complete (CR), 29% very good partial (VGPR), and 46% partial (PR)). The ORR post ASCT was 89% (CR 45%, VGPR 22%, PR 21%). Non relapse mortality was 1% and 3% at 100 days and 1 year respectively. At a median follow up of 31 months (7-90), 69 patients (38%) had relapsed. Median progression free survival (PFS) was 29 months with 1 and 3 years PFS of 79.3% and 61.5% respectively (Fig. 1). The OS was not reached. One and 3 years OS were 93% and 88% respectively (Fig. 1). Univariate analysis showed that time to transplant > 12 months was associated with poor outcome and decreased overall survival (HR 3.30, p = 0.008). High risk genetic profile was also found to be associated with decreased overall survival although this was not statistically significant (HR 2.31, p = 0.070). Multivariate analysis found that only time to transplant > 12 months was an independent predictor of decreased OS. Significant predictors for disease progression were high risk genetic profile and time to transplant > 12 months in patients receiving 2 or more treatments before ASCT. Conclusion: Induction with novel agents followed by HDT and ASCT improves CR rate, in our case from 9% to 45%. Median PFS (29 months) was comparable to other published data. OS was not been reached after a median follow up of 31 months. Predictors of progression include high risk genetic profile and time to transplant > 12 months. The only significant predictor for survival was time to transplant. Our study suggests that an early transplant may improve OS and PFS. An extended analysis will be presented at the meeting. Disclosures: Phillips: NCI/NIH: Research Funding; NCCM Grant: Research Funding; ARRA RC2 Grant: Research Funding. Byrd:Genzyme Corporation: Research Funding.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4111-4111
Author(s):  
Victor H Jimenez-Zepeda ◽  
Donna E. Reece ◽  
Suzanne Trudel ◽  
Christine Chen ◽  
Andrew Winter ◽  
...  

Abstract Abstract 4111 In multiple myeloma (MM), the impact of complete response (CR) and very good partial response (VGPR) achievement has been shown mostly after introduction of high dose therapy (HDT) supported by autologous stem cell transplant (ASCT). Recently, the IFM group reported the impact of achievement of CR and VGPR in double ASCT. The purpose of this study is to confirm the prognostic value of CR/VGPR in a large group of patients treated with single ASCT. Methods All consecutive patients who underwent single ASCT at Princess Margaret Hospital between January 2000 and December 2007 were evaluated. Patients were mobilized with cyclophosphamide and G-CSF and majority were conditioned with melphalan 200mg/m2. Response to therapy was assessed according to the IMWC including VGPR. Progression Free Survival (PFS) and Overall Survival (OS) were measured from transplant date to the date of death or last follow-up. OS and DFS were analyzed using the Kaplan-Meier Method. The Cox proportional hazard model was used to assess CR and VGPR and some other prognostic markers at presentation such as age, B2Mg> 460 μmol/L, LDH> 350 IU/L, CRP> 20mg/L, albumin<35g/L and creatinine > 200 μmol/L. All p-values were 2-sided and statistically significant if <0.05. Results 788 patients were identified for the study; their median age was 56 years (30–73). Patient's characteristics are listed in Table 1. Response was assessed at day 100 after ASCT and showed a CR of 6%, PR of 37.5%, and VGPR of 53% (Overall Response rate of 95.5%). Median OS and PFS for the group were 77.43 months and 20.63 months respectively. The median OS and PFS were significantly better for patients who achieved CR/VGPR, 104.5 months versus 51.7 months, and 26.3 months versus 13.53 months respectively. With a median follow-up of 44 months there is no significant difference in OS for those patients who achieved VGPR/CR after induction therapy with novel agents. However, PFS is better in those patients receiving novel agents who achieved VGPR/CR (Median PFS of 24.63months versus 12.4 months respectively (p=0.01). Multivariate analysis shows CR/VGPR as an independent prognostic factor for OS and PFS (Fig 1 and 2). B2Mg> 460 μmol/L, LDH> 350 IU/L, CRP > 20mg/L, albumin<35g/L and creatinine > 200 μmol/L failed to be important factor for survival in the multivariate analysis. Our data suggests that VGPR/CR is clearly important in the pre-novel agents era and for the smaller group of patients who had novel agents induction there is a benefit in PFS and with a longer follow-up perhaps in OS. In conclusion, VGPR/CR remains a simple and powerful indicator in the context of single ASCT and should be considered a relevant objective for MM treatment. Table 1. Clinical characteristics of patients with Multiple Myeloma undergoing single ASCT Clinical characteristic N=788 Median Range % Age (years) 58 31–74 Male 59.4% Female 40.6% Hemoglobin (g/L) 114 54–180 Creatinine (μmol/L) 107 28–1409 B2-microglobulin ((μmol/L) (N=718) 508 260–7270 Albumin (g/L) (N=650) 38 23–54 IgG 51.1% IgA 31.3% IgM 0.4% IgD 0.7% Biclonal 9.9% Not Detected 6.6 Kappa 59.4% Lambda 32.9% Biclonal 2% Not Detected 5.7% Calcium (μmol/L) 2.29 1.62–4.66 LDH (IU/L) (N=754) 235 50–1470 Induction Treatment: 52.2% VAD 22.8% Dexamethasone 6.3% TD 2.3% CP 3.8% DPACE/DTPACE 1.7% DVD 8% CyBORD 2% VD Ab: VAD: Vincristine, Adriamycin and dexamethasone, TD: Thalidomide and Dexamethasone; CP: Cyclophosphamide and Prednisone, DVD: Doxil, Velcade and Dexamethasone, CyBORD: Cyclophosphamide, Bortezomib and Dexamethasone and VD: Valcade and Dexamethasone Disclosures: Jimenez-Zepeda: J & J: Honoraria. Reece:Bristol, Meyers, Squibb: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Johnson&Johnson: Research Funding; Merck: Honoraria, Research Funding; Otsuka: Honoraria, Research Funding; Millennium: Research Funding; Amgen: Honoraria. Chen:Celgene Corporation: Consultancy, Honoraria, Research Funding. Kukreti:Celgene: Honoraria.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3975-3975
Author(s):  
Ho Sup Lee ◽  
Yang Soo Kim ◽  
Chang-Ki Min ◽  
Je-Jung Lee ◽  
Kihyun Kim ◽  
...  

Abstract Background: There have been many advances in treatments for multiple myeloma (MM). Recently, novel agents such as thalidomide, bortezomib, and lenalidomide have been developed for myeloma treatment. thalidomide was the first novel agent introduced that improved the overall response rate (ORR) and prolonged survival in transplant eligible or ineligible patients with multiple myeloma. It was first confirmed that thalidomide was active in patients with relapsed and/or refractory MM; since then, thalidomide has become an important part of MM treatment, as initial therapy for previously untreated patients, as maintenance therapy following definitive treatment, and as salvage therapy. Until now, the efficacy of thalidomide maintenance has been controversy in some studies. The purpose of this study was estimate necessity of thalidomide maintenance for improving survival in transplantation eligible patients with MM in real clinical fields. Methods: Data from patients at thirteen university hospitals in South Korea between December 2005 and May 2013 were collected retrospectively. All included patients were treated with induction chemotherapy followed by autologous stem cell transplantation (ASCT) and then with or without maintenance. The included patients were treated with thalidomide based regimens (TD;128 (50.6%), CTD; 96 (37.9%), TAD; 11 (4.3%)), mostly or other conventional regimens such as vincristine, doxorubicin and dexamethasone (VAD; 10 (4.0%), and others; 8 (3.2%)) as induction chemotherapy. And then patients received ASCT. However, patients were excluded underwent tandem ASCT or Allogeneic stem cell transplantation. The number of patients treated with thalidomide maintenance for more than six months after ASCT were 74 (29.2%) without maintenance were 179 (70.8%). The differences of survival were estimated in two groups which were defined to include patients treated with or without thalidomide maintenance. Patients who suffer from progression or relapse after ASCT were received salvage chemotherapy such as bortezomib based or other novel agents based regimen. The progression free survival (PFS) was defined duration from the date of starting induction chemotherapy to the date of disease progression, relapse, or death from any causes after ASCT. The definition of overall survival (OS) was calculated from the date of diagnosis to the date of death from any causes or final follow-up date. The postrelapse survival (PRS) was defined duration from the date of relapse after ASCT to the date of disease progression, relapse, or death from any causes. Results: The median age of the 253 patients was 57 years (range, 33-75 years) and the male to female ratio was 1.07:1.0. The response rates before ASCT were following: CR or stringent CR (sCR) in 93 (36.7%), VGPR in 63 (24.9%), PR in 86 (34.0%), and < PR in 7 (2.8%). The reason for the higher ORR in this study compared to other studies was that it included patients who were treated with thalidomide induction chemotherapy and who underwent ASCT. Most of these patients achieved more than PR or PR because the South Korean national health insurance only allowed ASCT in such patients. The differences of 3-year PFS of patients with or without maintenance were 66.1% vs 43.0%, p=0.003. The 3-year OS were 91.7% vs 84.5%, p=0.091. And the differences of PRS were not shown in two groups (11.63 vs 10.00 months, p=0.790). Conclusion: Patients treated with thalidomide maintenance after ASCT were presented higher PFS but not shown higher OS. However, long term use of thalidomide as maintenance therapy was not interfere with efficacy of salvage chemotherapy in patients suffered from progression or relapse after ASCT. So, we suggest that thalidomide maintenance might be useful for improving survival by lowering relapse or progression rates and not interfere with efficacy of salvage chemotherapy in real clinical field. In the future, further prospective studies will be needed to confirm the role of thalidomide maintenance therapy for prolonged survival in patients with MM who are treated with novel agents such as thalidomide, bortezomib, or lenalidomide. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2358-2358 ◽  
Author(s):  
Seema Niphadkar ◽  
Indumathy Varadarajan ◽  
Tiffany Pompa ◽  
Kevin Y Hou ◽  
Kathleen Degen ◽  
...  

Abstract Background: Induction chemotherapy followed by autologous stem cell transplantation (ASCT) is considered a standard of care for appropriate patients with newly diagnosed multiple myeloma (MM), but with the rapid expansion of available treatments, the role of ASCT has been questioned. Numerous studies have shown an improvement in complete response (CR) and progression free survival (PFS) with ASCT but our study is a cost comparison between novel agents and ASCT. We aimed to compare the cost effectiveness of ASCT versus non-transplant regimens in relation to PFS. Methods: We queried the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample (NIS) between 2008 and 2013 using the ICD-9 code 203.00 for MM and V42.81 for ASCT in the primary and secondary diagnosis fields. The analysis included patients who were 18 years or older. We monitored the trends in ASCT with regards to cost of a transplant admission and length of stay (LOS). Cost of hospitalization was adjusted for inflation in reference to the year 2011 and cost to charge ratio. Literature regarding common treatment regimens, response rates, duration of treatment, and PFS was reviewed. The assumption was made that transplant eligible patients that did not undergo transplant would be treated as though they were transplant ineligible. Gay et al 2015 showed a 43.4-month (mo) median PFS with 4 cycles of Rd followed by ASCT and lenalidomide maintenance until progression or toxicity. The cost of novel regimens was estimated using the one month commercial cost described by Roy et al and wholesale acquisition costs for new agents not described by the study which were adjusted using adjunct cost described by the study. A standard weight of 70 kg was used for agents requiring dose calculations. The cost of novel agents for an equivalent duration of 43.4 mo was estimated. Results: A total of 44778 (weighted n=9039) hospitalizations for MM (Male 55.9%, Caucasian 57.9%, peak incidence 65-79 yrs) occurred from 2008-2013. The average length of stay during ASCT admission was 11.4 +/- 0.4 days with a cost of $109,856 +/-5749.83. There has been a 16.89% decrease in LOS and 1.99% increase in the cost of ASCT (p<0.05). Gay et al showed a 43.4 mo PFS with 4 cycles Rd ($46,216) followed by ASCT ($109,856) and lenalidomide maintenance (~35.4 mo $564,453 adjusted for cost of office visits and lab work) for a total of $720,525 Conclusion: Rd + ASCT + R maintenance is efficacious for the treatment of newly diagnosed MM. The cost associated with the induction and transplant represents only 22% of the total cost, whereas lenalidomide maintenance makes up 78%. Considering secondary risks and the cost involved with lenolidomide maintenance, further investigation is warranted regarding the optimal duration of maintenance therapy and resultant progression free survival. It also raises the need for alternative options for maintenance therapy. Bortezomib and ixazomib are both more cost effective options and studies are in progress to assess their efficacy in PFS in the maintenance setting. Studies using novel agents for induction prior to ASCT are ongoing and have yet to reach an optimal duration of therapy. Table 1 shows that most of the novel agents used in combination regimens are more expensive that ASCT. Although most patients would not remain on one of these regimens for 43.4 mo, they would presumably progress through multiple lines of therapy during the 43.4 mo of PFS that ASCT provides. In an era of cost consciousness, ASCT should continue to be an integral component of MM treatment. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2019 ◽  
Vol 133 (18) ◽  
pp. 1953-1963 ◽  
Author(s):  
Thierry Facon ◽  
Jae Hoon Lee ◽  
Philippe Moreau ◽  
Ruben Niesvizky ◽  
Meletios Dimopoulos ◽  
...  

Abstract The phase 3 CLARION study compared carfilzomib-melphalan-prednisone (KMP) with bortezomib-melphalan-prednisone (VMP) in transplant-ineligible newly diagnosed multiple myeloma (NDMM) patients. Patients were randomized 1:1 to KMP or VMP for nine 42-day cycles (C). Patients received carfilzomib on days (D) 1, 2, 8, 9, 22, 23, 29, 30 (20 mg/m2: C1D1, C1D2; 36 mg/m2 thereafter) or bortezomib on D1, 4, 8, 11, 22, 25, 29, 32 (1.3 mg/m2; D4, 11, 25, 32 omitted for C5-9). Melphalan (9 mg/m2) and prednisone (60 mg/m2) were administered on D1-4. The primary endpoint was progression-free survival (PFS). Nine hundred fifty-five patients were randomized (intention-to-treat population: KMP, n = 478; VMP, n = 477). Median PFS was 22.3 months with KMP vs 22.1 months with VMP (hazard ratio [HR], 0.906; 95% confidence interval [CI], 0.746-1.101; P = .159). Median overall survival was similar and not reached in either group (HR, 1.08; 95% CI, 0.82-1.43). Overall response rate was 84.3% for KMP and 78.8% for VMP. Complete response rate was 25.9% for KMP and 23.1% for VMP. Minimal residual disease–negative rates were 15.7% (KMP) and 15.5% (VMP). Adverse events (AEs) of interest (any grade) occurring with a ≥5% higher patient incidence in the KMP arm were acute renal failure (13.9% [KMP] vs 6.2% [VMP]) and cardiac failure (10.8% vs 4.3%). Grade ≥3 AE rates were 74.7% (KMP) and 76.2% (VMP). Grade ≥2 peripheral neuropathy was lower for KMP vs VMP (2.5% vs 35.1%). Treatment with KMP in CLARION did not yield a statistically significant difference in PFS vs VMP. This trial was registered at www.clinicaltrials.gov as #NCT01818752.


2017 ◽  
Vol 24 (5) ◽  
pp. 361 ◽  
Author(s):  
W.M. Jose ◽  
K. Pavithran ◽  
T.S. Ganesan

Purpose We assessed response to treatment, toxicity, time to progression, progression-free survival, and overall survival in patients newly diagnosed with multiple myeloma who were ineligible for or unwilling to undergo transplantation and who were treated with a combination of lenalidomide and low-dose dexamethasone for a fixed 6 cycles in a resource-constrained environment.Methods This pragmatic study, conducted in a single tertiary cancer centre in South India, enrolled patients from May 2009 till April 2011. Treatment included lenalidomide 25 mg daily for 21 days, with dexamethasone 40 mg on days 1, 8, 15, and 22 of a 28-day cycle, for 6 cycles. Response was evaluated after the 3rd and 6th cycles of treatment. All patients were followed for 5 years.Results The study enrolled 51 patients. Median age in the group was 61 years (range: 38–76 years). Immunoglobulin G or A myeloma constituted 70.6% of the diagnoses, and light-chain myeloma constituted 29.4%. Stages i, ii, and iii (International Staging System) disease constituted 21.4%, 28.6%, and 50% of the diagnoses respectively. All patients were transplantation-eligible, but 34 (66.7%) refused for economic reasons. After treatment, 19.6% of the patients achieved a stringent complete response; 35.3%, a complete response; 5.9%, a very good partial response; and 29.4%, a partial response, for an overall response rate of 90.2%. Stable disease was seen in 3.9% of patients, and progressive disease, in 5.9%. Grade 3 or greater nonhematologic and hematologic toxicity occurred in 35.2% and 11.7% of patients respectively. Pulmonary embolism occurred in 1 patient. No patient experienced deep-vein thrombosis or peripheral neuropathy. The median follow-up duration was 66 months. All patients experienced disease progression. Median progression-free survival was 16 months. In 10 patients, re-challenge with lenalidomide and dexamethasone achieved a second complete response. At the time of writing, 19 patients had died. The overall survival rate at 5 years was 62.74%. Median overall survival is not yet reached.Conclusions In a resource-constrained setting, lenalidomide with low-dose dexamethasone is an effective treatment with acceptable toxicity in patients newly diagnosed with multiple myeloma and not planned for transplantation. Complete responses were significantly more frequent than reported in the Western literature. Occurrence of clinical deep-vein thrombosis was rare, but hyperglycemia was common. An abbreviated course of treatment is suboptimal in multiple myeloma. Maintenance regimens should be advocated.


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