scholarly journals Multiple Myeloma Patients with Lenalidomide-Associated Skin Rash Have a Favorable Prognosis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4532-4532 ◽  
Author(s):  
Ayumi Kojima ◽  
Yuka Tanaka ◽  
Yuta Kimura ◽  
Daisuke Tsuchimoto ◽  
Rina Etani ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Skin Rash ◽  
Research Funding ◽  
Kinase Inhibitors ◽  
Performance Status ◽  
Progression Free Survival ◽  
Rank Test ◽  
Free Survival ◽  
The Relationship

Abstract Background: Lenalidomide, one of the immunomodulatory drugs, is an important component of treatment for multiple myeloma. Lenalidomide inhibits the proliferation of tumor cells via antiangiogenesis, induces apoptosis and acts directly on the immune system and tumor microenvironment. Immunomodulatory effects of lenalidomide notably stimulate the production of cytokines and activation of T-cells and natural killer cells. Skin rash is a frequent adverse event of lenalidomide. Some studies have shown a correlation between the efficacy of anti-cancer agents such as tyrosine kinase inhibitors and the development of skin rash. However, the relationship between the development of lenalidomide-associated skin rash and its efficacy is unclear. We conducted a retrospective survey to clarify whether development of skin rash correlates with the efficacy of lenalidomide. Materials and Methods: All patients with multiple myeloma who received lenalidomide at 9 hospitals in Japan from July 2009 to December 2015 were serially registered. The chart review was performed for all identified patients to obtain the following information; age, sex, performance status at the initiation of lenalidomide, International Staging System (ISS) classification, prior chemotherapy regimen, tumor response, development of skin rash and clinical outcomes. A log-rank test was used to assess the relationship between the presence of skin rash and survival. A two-sided p < 0.05 was considered statistically significant. This study received approval from the appropriate ethics committees. Results: We identified 215 patients (92 women and 123 men), with a median age was 69 years (range, 39-86 years). Types of myeloma were as follows: 139 patients of IgG, 43 of IgA, and 29 of Bence-Jones protein. ISS was available for 204 patients, and of these, 63, 73, and 68 patients were classified as ISS stage I, II, and III, respectively. The median number of prior therapies was 2 (range, 0-6); 161 (74.9%) and 46 patients (21.4%) had previously received bortezomib and thalidomide, respectively. Fifty patients (23.3%) had undergone previous autologous stem cell transplantation. Sixty-five patients (30.2%) developed a skin rash after lenalidomide initiation, and the median time to onset of skin rash was 12 days. The patients with and without skin rash were similar with respect to age, type of myeloma, and ISS. The median follow-up of survivors was 28.9 months (range, 1.7-80.3 months). The progression-free survival and overall survival were better in patients who had skin rash than in those who did not (p = 0.009 and p = 0.033, respectively) (Figures A and B). Conclusions: In this study, the progression-free survival and overall survival among patients with skin rash during lenalidomide therapy was significantly superior to the patients without skin rash. Lenalidomide-associeated skin rash in patients with multiple myeloma may be a predictive factor of their clinical outcome. Figure Figure. Disclosures Nagai: Takeda: Honoraria, Research Funding; Janssen: Research Funding; Mundipharma KK: Research Funding.

scholarly journals Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD) Compared to Bortezomib, Thalidomide and Dexamethasone (VTD) As Induction Therapy for the Treatment of Transplant Eligible Multiple Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4505-4505 ◽  
Author(s):  
Victor Jimenez-Zepeda ◽  
Nizar J. Bahlis ◽  
Peter Duggan ◽  
Rafael Alonso ◽  
Juan José Lahuerta ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Treatment Regimen ◽  
Research Funding ◽  
Progression Free Survival ◽  
Categorical Variables ◽  
Rank Test ◽  
Fisher Exact Test ◽  
Similar Response ◽  
Free Survival

Abstract Introduction: Cyclophosphamide, bortezomib and Dexamethasone (CyBorD) has become the standard frontline approach for the treatment of multiple myeloma (MM) in many centers across Canada. A recent study led by the IFM group showed that the triplet combination of bortezomib, thalidomide and dexamethasone is superior as an induction regimen compared to CyBorD for patients undergoing ASCT. Based on the above-mentioned, we aimed to compare the effect of CyBorD and VTD for the treatment of transplant eligible MM patients in 2 different centers from Canada and Spain. Patients and Methods: The primary objective was to assess ORR and ³VGPR rates after induction and at day-100 post-ASCT, as well as MRD assessed by flow cytometry. Two-sided Fisher exact test was used to test for differences between categorical variables. A p value of <0.05 was considered significant and survival curves were constructed according to the Kaplan-Meier method and compared using the log rank test. Results: 101 patients have received CyBorD and 23 have received VTD. Clinical characteristics are shown in Table 1. At the time of analysis, 90 and 19 patients in the CyBorD and VTD are alive of which 25 and 9, respectively, have progressed. ORR and VGPR rates after a median of 4 cycles of induction were 94% and 56.4% for patients treated with CyBorD, and 91% and 78.2% for VTD, respectively (p=0.3 and 0.05). At day-100 post-ASCT, a ³VGPR rate of 84% and 94% was observed for the CyBorD and VTD groups, respectively (p=0.2). MRD negativity and CR rates were higher in the group receiving VTD (36.8% vs 27%, and 61% vs 38%, p=0.3 and 0.01). Furthermore, median OS and PFS did not differ among both groups (p=0.8 and 0.9, respectively) (Fig1a and Fig1b). In Conclusion: CyBorD and VTD appeared to be effective treatment options for transplant-eligible myeloma patients with similar response rates. Our study is in agreement with that reported by the IFM group, showing a higher rate of³VGPR after induction and day-100 post-ASCT in the VTD group. MRD negativity and CR rate appears also higher in the VTD group suggesting a higher degree of response by using animmunomodulatory drug and a proteasome inhibitor together. Overall Survival according to treatment regimen Overall Survival according to treatment regimen Figure 1 Progression-Free survival according to treatment regimen Figure 1. Progression-Free survival according to treatment regimen Disclosures Jimenez-Zepeda: Takeda: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Celgene, Janssen, Amgen, Onyx: Honoraria. Bahlis:Janssen: Consultancy, Honoraria, Other: Travel Expenses, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria; Onyx: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Other: Travel Expenses, Research Funding, Speakers Bureau; BMS: Honoraria. Neri:Celgene and Jannsen: Consultancy, Honoraria.

scholarly journals Prospective Comparison Study of Prognostic Value of MRD Detected By 8-Color MFC (EuroFlow-NGF) and NGS in Patients with Multiple Myeloma in ASCT Setting

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3946-3946
Author(s):  
Takeshi Yoroidaka ◽  
Hiroyuki Takamatsu ◽  
Mitsuhiro Itagaki ◽  
Satoshi Yoshihara ◽  
Kota Sato ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
High Risk ◽  
Research Funding ◽  
Prognostic Value ◽  
Progression Free Survival ◽  
Comparison Study ◽  
Next Generation ◽  
Free Survival ◽  
Prospective Comparison

Abstract Background: Novel agents capable of inducing deeper responses dramatically improve the prognosis of patients with multiple myeloma (MM). Innovative technologies such as multiparameter flow cytometry (MFC) and next-generation sequencing (NGS) are utilized to assess minimal residual disease (MRD) for further stratification of patients who achieve a complete response (CR). EuroFlow-next-generation flow (EuroFlow-NGF) is one of the gold standard MFC methods. Recently, both NGF and NGS have been used in many clinical trials to assess MRD levels associated with progression-free survival (PFS) and overall survival (OS). The present study prospectively assessed MRD levels by both NGF and NGS to elucidate the prognostic impact of both methods and clarify their characteristics in MM patients in an autologous stem cell transplantation (ASCT) setting. Methods: We prospectively assessed the response in Japanese patients with newly diagnosed MM who underwent ASCT and lenalidomide-based maintenance therapy at multiple Japanese medical centers between September 2016 and July 2021. The diagnosis of MM and patients' responses to therapy were assessed using the IMWG criteria. Only patients with CR or stringent CR on days 100-365 post-ASCT were included, and bone marrow (BM) samples were obtained to assess MRD. Four milliliters of BM was divided equally. Cells derived from 2 mL BM were analyzed by the NGF method (Flores-Montero et al., Leukemia 2017) at Kanazawa University, and DNA extracted from the remaining 2 mL BM cells was processed by Adaptive Biotechnologies' standardized NGS-MRD assay (Seattle, WA) (Ching et al., BMC Cancer 2020) to assess MRD levels. MRD levels in BM were also monitored at 1-year (± 20 days) and 2-year (± 20 days) post-ASCT. The prognostic value of MRD levels in BM was assessed, and their correlation between NGF and NGS was compared at a cut-off value of 1×10 -5. Sustained MRD negativity was defined as the maintenance of MRD negativity in the BM for more than 6 months. BM cells were analyzed for high-risk cytogenetics (del(17p), t(4;14), and t(14;16)) by FISH. Results: A total of 60 patients (male = 29, female = 31) underwent bortezomib-based induction therapy, ASCT conditioned with high-dose melphalan, and lenalidomide-based maintenance. The median age was 62 years at the ASCT (range 36-71; ISS 1 [n = 13], 2 [n = 24], and 3 [n = 23]). Thirty-three percent of patients showed high-risk chromosomal abnormalities (del17p (n=11), t(4;14) (n=10), t(14;16) (n=2)), 3 patients had double hit diseases, and five patients had extramedullary diseases. With a median follow-up of 3 years, the 3-year progression-free survival (PFS) and 3-year overall survival (OS) rates were 69.2% and 94.2%, respectively. In total, 148 samples were analyzed using NGF and 138 were analyzed using NGS. The rates of MRD negativity at least once using NGF and NGS were 80% and 61%, respectively. The patients who achieved at least one MRD negativity exhibited significantly better 3-year PFS (82.9% by NGF; 84.8% by NGS) than those who did not (P &lt; 0.0001, 0% by NGF; P = 0.005, 49.1% by NGS). Patients who sustained MRD negativity for more than 6 months also showed significantly better 3-year PFS (96.7% by NGF; 92.3% by NGS) compared with those without sustained MRD negativity (Figure; P &lt; 0.0001, 37.1% by NGF; P &lt; 0.01, 50.9% by NGS). The MRD levels between the NGF and NGS methods were significantly correlated with each other (r = 0.9295, P &lt; 0.0001). Among the 17 patients who developed PD after ASCT, seven cases showed discrepancies in the MRD results and two cases in which one case was MRD-positive and the other was MRD-negative by both methods progressed with extramedullary diseases. Five of the seven cases were MRD-positive by NGS and MRD-negative by NGF. Conclusions: In this prospective comparison study of MRD assessment in BM cells using EuroFlow-NGF and NGS approaches, MRD levels highly correlated with each other, and MRD negativity and sustained MRD negativity were significantly associated with prolonged PFS. Multiple MRD assessments by NGF or NGS are essential for predicting durable remission and prolonged clinical outcomes. Figure 1 Figure 1. Disclosures Takamatsu: Bristol-Myers Squibb: Honoraria, Research Funding; Adaptive Biotechnologies, Eisai: Honoraria; SRL: Consultancy; Janssen: Consultancy, Honoraria, Research Funding. Yoshihara: Bristol-Myers Squibb: Honoraria; Janssen: Honoraria; Novartis: Honoraria. Matsumoto: Sanofi: Honoraria; Janssen: Honoraria; Ono: Honoraria; Bristol-Myers Squibb: Honoraria. Yamashita: Janssen: Honoraria; Bristol-Myers Squibb: Honoraria; celgene: Honoraria; Takeda: Honoraria. Fuchida: Takeda Pharmaceutical Co., Ltd.: Honoraria; Ono Pharmaceutical Co., Ltd.: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Sanofi: Honoraria; Bristol-Myers Squibb Co., Ltd.: Honoraria; Celgene Co., Ltd.: Honoraria. Hiragori: BML: Current Employment. Suzuki: Amgen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; ONO: Honoraria; Novartis: Honoraria; Sanofi: Honoraria; Abie: Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding. Nakao: Symbio: Consultancy; Kyowa Kirin: Honoraria; Novartis Pharma: Honoraria; Alexion Pharma: Research Funding. Durie: Amgen: Other: fees from non-CME/CE services ; Amgen, Celgene/Bristol-Myers Squibb, Janssen, and Takeda: Consultancy.

Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD) Compared to Lenalidomide and Dexamethasone (LD) for the Treatment of Non-Transplant Eligible Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1845-1845 ◽  
Author(s):  
Victor H Jimenez-Zepeda ◽  
Christopher P. Venner ◽  
Andrew Belch ◽  
Irwindeep Sandhu ◽  
Tatiana Nikitina ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Treatment Regimen ◽  
Research Funding ◽  
Clinical Characteristics ◽  
Progression Free Survival ◽  
Categorical Variables ◽  
P Value ◽  
Similar Response ◽  
Free Survival

Abstract Introduction: Cyclophosphamide, bortezomib and Dexamethasone (CyBorD) has become the standard frontline approach for the treatment of multiple myeloma (MM) in many centers across Canada. In the non-transplant eligible setting, recently a randomized controlled trial reported on the impact of Lenalidomide and Dexamethasone (LD), showing that this doublet-therapy is a feasible and efficacious combination. Based on the above-mentioned success of the LD combination, we aimed to compare the effect of CyBorD and LD for the treatment of non-transplant eligible MM (NTE) patients in the Alberta Myeloma and Dysproteinemia Program (AMDP). Patients and Methods: The primary objective was to assess ORR and PFS for NTE MM patients treated with CyBorD and LD. The recommended CyBorD regimen was as follows: bortezomib 1.3-1.5 mg/m2 SC or IV days 1, 8, 15 of a 28 day cycle (as of August, 2013 we adopted the a strategy whereby bortezomib can also be given on day 22), cyclophosphamide 300 mg/m2 PO days 1, 8, 15 and 22 and dexamethasone 20-40 mg PO days 1, 8, 15 and 22 with an aim to deliver a minimum of 9 cycles of treatment. LD was given at 25 mg days 1-21 of a 28-day cycle with Dexamethasone 20-40 mg PO days 1, 8, 15 and 22. Dose adjustments were at the discretion of the treating physician. Two-sided Fisher exact test was used to test for differences between categorical variables. A p value of <0.05 was considered significant and survival curves were constructed according to the Kaplan-Meier method and compared using the log rank test. Results: Ninety-one patients have received CyBorD and 56 have received LD. Clinical characteristics are shown in Table 1. At the time of analysis, 64 and 32 patients in the CyBorD and LD are alive of which 10 and 11, respectively, have progressed, ORR and VGPR rates were 85.7% and 56% for patients treated with CyBorD, and 83.9% and 64% for LD respectively (p=0.3). Estimated median OS was 40 months for CyBorD compared to 66 months for LD (p=0.156). In addition, median PFS was longer for LD patients compared to CyBorD (26 months vs 16.4 months, p=0.018). The rate of treatment discontinuation was similar between both groups (8.7% vs 10%, p=0.3). In Conclusion: CyBorD and LD appeared to be effective treatment options for NTE myeloma patients with similar response rates. Recognizing the limitations of a retrospective series, it is interesting to note a longer PFS and a trend towards better PFS in the LD group, however, longer follow-up and prospective validation is still required. Table 1. Clinical Characteristics Characteristic CyBorD, n=91 LD, n=56 P value Age (median) 73.9 73.6 0.2 GenderMaleFemale 57 (62.6%)34 (37.4%) 34 (60.7%)22 (39.3%) 0.8 B2microglobulin (µmol/L) 4.9 4.89 0.4 Albumin (g/L) 35 36 0.7 Stage IStage IIStage III 17.7%35.4%46.9% 23.5%37.2%39.3% 0.6 BMPC (%) 32 37.5 0.6 Heavy chain:IgGIgAFLC onlyIgDIgMBiclonal 501018113 26179010 0.068 Response rateORRCR/nCRVGPRPR 85.7%23%31.8%30.7 83.9%28%37.5%17.8% 0.3 Ab: BMPC: Bone marrow plasma cell Figure 1. Overall Survival according to treatment regimen Figure 1. Overall Survival according to treatment regimen Figure 2. Progression-Free survival according to treatment regimen Figure 2. Progression-Free survival according to treatment regimen Disclosures Jimenez-Zepeda: Celgene: Honoraria; Amgen: Honoraria; J&J: Honoraria. Venner:J&J: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria. Sandhu:Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Duggan:Celgene: Honoraria; Jansen: Honoraria. Neri:Celgene: Research Funding. Bahlis:Johnson & Johnson: Speakers Bureau; Johnson & Johnson: Research Funding; Amgen: Consultancy; Johnson & Johnson: Consultancy; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau.

Analysis of 179 Patients with Newly Diagnosed Multiple Myeloma (MM) Treated with Novel Agents Followed by Autologous Stem Cell Transplantation (ASCT): a Retrospective Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1343-1343
Author(s):  
Joyce Habib ◽  
Neil Dunavin ◽  
Gary Phillips ◽  
Patrick Elder ◽  
Meaghan Tranovich ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
High Risk ◽  
Research Funding ◽  
Progression Free Survival ◽  
Novel Agents ◽  
Genetic Profile ◽  
Newly Diagnosed ◽  
Free Survival

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.

scholarly journals Immunoglobulin Recovery after ASCT for Patients with Multiple Myeloma: Impact on Overall Survival and Progression-Free Survival

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2263-2263
Author(s):  
Victor Jimenez-Zepeda ◽  
Peter Duggan ◽  
Paola Neri ◽  
Ahsan Chaudhry ◽  
Jason Tay ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Research Funding ◽  
Progression Free Survival ◽  
Partial Recovery ◽  
Maintenance Strategy ◽  
Free Survival ◽  
Immune Enhancement ◽  
The Impact

Abstract Introduction Immunoparesis, defined as suppression of uninvolved immunoglobulins (Igs), has been described as one of the most common indicators of immune dysfunction in patients with multiple myeloma (MM). The role of immunoglobulin recovery, however, has not been properly evaluated, in particular in the setting of immunomodulatory therapy. In the present study, we aimed to assess the impact of immunoparesis and Igs recovery after ASCT on Overall and Progression-Free survival (OS and PFS). Methods All consecutive patients undergoing ASCT at our center from 01/2004 to 03/2016 were evaluated. All patients received induction chemotherapy before undergoing auto-SCT. Patients received conditioning with either HDM at 200 mg/m2 (or adjusted as per renal failure) or HDM with Bortezomib (Bor-HDM). Definitions of response and progression were used according to the EBMT modified criteria. Immunoglobulin recovery was assessed at 12 months post-ASCT in those cases where immunoparesis was noted at diagnosis. Results Clinical characteristics are shown in Table 1. Decrease of uninvolved Ig's was noted in 94% of cases. At the time of analysis, 69.2% of patients are alive and 54.9% have already progressed, respectively. Median OS did not differ between patients with or without immunoparesis (p=0.851). With regards to Ig recovery at 12 months post-ASCT, median OS was longer for those patients with complete or partial normalization of Ig's compared to those with no recovery at all (Estimate median OS of 97, 77 and 69 months, respectively, p=0.008) (Fig1a). In addition, median PFS was longer for those patients with normalization or partial recovery of Ig's at 12 months post-ASCT (median of 40.3 and 38 months, compared to 24.6 months for those without Ig recovery, p=0.002) (Fig1b). Furthermore, 121 patients receiving lenalidomide maintenance were evaluated, 49% of cases exhibited complete or partial recovery of Ig's at 12 months post-ASCT, compared to 40% for those cases that were not treated with any maintenance strategy (p=0.6). In conclusion, Immunoglobulin recovery at 12 months post-ASCT is an important factor to predict for better progression-free and overall survival. The use of lenalidomide as a maintenance strategy did not seem to affect the process of Ig recovery. Based on our observations, the use of immune enhancement strategies in the post-transplant setting seem appealing and requires further investigation. Disclosures Jimenez-Zepeda: Janssen: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Celgene, Janssen, Amgen, Onyx: Honoraria. Neri:Celgene and Jannsen: Consultancy, Honoraria. Bahlis:Celgene: Consultancy, Honoraria, Other: Travel Expenses, Research Funding, Speakers Bureau; BMS: Honoraria; Onyx: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: Travel Expenses, Research Funding, Speakers Bureau.

Predictors Of Survival Outcomes In Phase I Relapsed Or Refractory Multiple Myeloma Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1958-1958
Author(s):  
R. Donald Harvey ◽  
Meagan S. Barbee ◽  
Ajay K. Nooka ◽  
Sungjin Kim ◽  
Zhengjia Chen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Phase I ◽  
Research Funding ◽  
Performance Status ◽  
Cell Activity ◽  
Subsequent Development ◽  
Progression Free Survival ◽  
Phase I Clinical Trials ◽  
Free Survival ◽  
Standard Risk

Abstract Objectives Categorization of response criteria for multiple myeloma (MM) is based on magnitude of change in serum and urine paraprotein values and normalization of free light chain ratio (rFLC). However, the association between improvements in these surrogate markers and patient outcomes is not validated in the phase I setting. Early measures of response would be beneficial for patients and agents to identify those likely to have prolonged disease-free intervals and to validate agent activity for rapid movement to subsequent development. Methods We identified 31 trials that met enrollment criteria of phase I, relapsed or refractory disease, and non-transplant study population. Clinical and demographic data collected included age, sex, race, ECOG performance status (PS) at entry, myeloma subtype and isotype, prior therapy, cytogenetics at study entry, date of progression, and date of expiration. Patients with t(4;14), del13, del17p, t(14;16), or t(14;20) were considered to have non-standard risk cytogenetics. Evaluation of the relationship between progression free survival (PFS) and change in plasma cell activity by the rFLC and magnitude of response in serum/urine paraprotein per IMWG criteria was performed. Landmark analyses occurred at cycle 2 and 4, 8, and 12 months. Progression free survival (PFS) at 12 months was the primary outcome of interest. Results Among 87 patients; 47 (54%) were female; 56 (64%) white, 29 (33%) black; 27 (31%) non-standard risk cytogenetics; ECOG PS 1 in 73 (84%); and median prior lines 5 (1-11). Eighty were evaluable for paraprotein changes, 71 for rFLC. Normalization of rFLC at 4 months conferred a PFS advantage (11.3 v 2.8 months, p = 0.038) (Table 1). Normalization of rFLC by 12 months was found to predict PFS (6.1 vs. 2.8 months, p = 0.015) and a longer OS (45 vs. 17.4 months, p = 0.002). Magnitude of response in paraprotein was found to predict and correlate linearly with PFS at all time landmarks (r2 = 0.769 to 0.952). Analysis of PFS by IMWG criteria and by quartiles of 50% changes were both linear (p < 0.001) (Figure 1). Conclusion These findings suggest that normalization of the rFLC and magnitude of paraprotein response are viable surrogate disease endpoints in phase I clinical trials of novel agents and combinations. The use of current IMWG criteria in the phase I setting is valuable, but the addition of time of response and alterations of response boundaries should be further evaluated in the setting of improved treatments. Disclosures: Kaufman: Onyx: Consultancy; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Janssen: Consultancy; Millenium: Consultancy; Merck: Research Funding. Lonial:Millennium: Consultancy; Celgene: Consultancy; Novartis: Consultancy; BMS: Consultancy; Sanofi: Consultancy; Onyx: Consultancy.

High-Risk Cytogenetics Multiple Myeloma: Impact of Consolidation and Maintenance

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2271-2271 ◽  
Author(s):  
Victor Jimenez-Zepeda ◽  
Peter Duggan ◽  
Paola Neri ◽  
Jason Tay ◽  
Fariborz Rashid-Kolvear ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Clinical Outcomes ◽  
Research Funding ◽  
Progression Free Survival ◽  
Categorical Variables ◽  
Rank Test ◽  
Fisher Exact Test ◽  
Free Survival ◽  
The Impact

Abstract Introduction MM is a very heterogeneous disease for which several new treatments have become available over the past decade. With the advent of novel agents, the outcomes of this disease have improved dramatically. Unfortunately, High-risk myeloma (HRM) defined by the presence of del(17p), t(4;14), t(14;16), del13q by conventional karyotype and hypodiploidy, continues to exhibit poorer outcomes. Based on the above mentioned, we aimed to assess the clinical outcomes of patients with HRM treated at our center. Methods All consecutive HRM patients who underwent single auto-SCT at Tom Baker Cancer Center (TBCC) from 01/2004 to March/2016 were evaluated. HRM was defined by FISH and conventional karyotype when available. Two-sided Fisher exact test was used to test for differences between categorical variables. A p value of <0.05 was considered significant. Survival curves were constructed according to the Kaplan-Meier method and compared using the log rank test. All statistical analyses were performed by using the SPSS 22.0 software. Results 73 consecutive patients with HRM underwent single auto-SCT at our Institution over the defined period. Clinical characteristics are shown in Table 1. Eighty-seven percent of patient received bortezomib-containing regimens as induction regimens. Day-100 response post-ASCT is seen in Table 1. Consolidation was given to 41.7% and maintenance to 79% of cases. At the time of analysis, 43 patients are still alive and 40 have already progressed. Median OS and PFS were 50.8 and 21.9 months, respectively for the whole group. Median OS was 50.4 months for the group receiving consolidation compared to 39 months for those without (p=0.1). In addition, median PFS was longer in the group treated with consolidation (NR, Estimate 25 months vs 13.5 months, p=0.02, Fig1a). Furthermore, OS and PFS were longer in the group receiving some form of maintenance compared to those without (56.3 and 22.5months vs 19.9 and 9 months, p=0.04 and 0.01, respectively) (Fig 1b and c). In conclusion, HRM is an aggressive form of myeloma where the OS and PFS are shorter than the standard risk MM. Consolidation and maintenance strategies seemed to increase both OS and PFS in our current report, but clinical outcomes are still poor. Novel strategies such as immune modulation,check-point inhibition, among others are needed to maximize the impact of the consolidation and maintenance phases in this group of patients. Progression-Free Survival and consolidation Progression-Free Survival and consolidation Figure 1 Overall survival and maintenance Figure 1. Overall survival and maintenance Figure 2 Progression-Free survival and maintenance Figure 2. Progression-Free survival and maintenance Disclosures Jimenez-Zepeda: Janssen: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Celgene, Janssen, Amgen, Onyx: Honoraria. Neri:Celgene and Jannsen: Consultancy, Honoraria. Bahlis:Amgen: Consultancy, Honoraria; BMS: Honoraria; Onyx: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Other: Travel Expenses, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Other: Travel Expenses, Research Funding, Speakers Bureau.

A Case Control Study of Syngeneic Transplantation Versus Autologous Transplantation for Multiple Myeloma: Two Decades of Experience at MD Anderson

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4613-4613
Author(s):  
Ghulam Rehman Mohyuddin ◽  
Muhammad Salman Faisal ◽  
Nina Shah ◽  
Qaiser Bashir ◽  
Chitra Hosing ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Research Funding ◽  
Plasma Cells ◽  
Progression Free Survival ◽  
Disease Status ◽  
Free Survival ◽  
First Remission ◽  
Equity Ownership ◽  
Relapsed Disease

Abstract INTRODUCTION: High-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-HCT) is the standard of care for eligible patients with newly diagnosed multiple myeloma. However, almost all patients eventually relapse possibly due to incomplete elimination of malignant plasma cells. For patients with an identical twin, syngeneic-HCT provides a tumor-free graft without the risk of graft vs. host disease. We hypothesized that syngeneic-HCT would result in better disease control than auto-HCT. METHODS : We identified 10 patients with multiple myeloma who underwent syngeneic-HCT at our institution from 1994 to 2014. Using a propensity score, we identified 48 controls that received auto-HCT during the same time interval. Matching was done for the year of transplant, age and disease status at auto-HCT (Table 1). Primary endpoint was progression-free survival (PFS). Secondary endpoints were complete remission (CR) rates and overall survival (OS). RESULTS: Baseline characteristics are shown in Table 1. The two groups were well matched, with no significant statistical differences in age, sex, race, stage at diagnosis, lines of therapy received, or disease status prior to transplant. At the time of transplant, 7 (70%) patients in the syngeneic cohort were in first remission, with 3 (30%) having relapsed disease. Similarly, 28 (58%) patients in the autologous cohort were in first remission, with 20 (41%) having relapsed disease (p value 0.49). Patient outcomes are summarized in Table 2. All patients engrafted, with a median time to engraftment of 11 and 10 days, for the syngeneic and auto-HCT cohorts respectively (p=0.22). There was no treatment related mortality in the first 100 days post-transplant in either of the cohorts. In the syngeneic group 8 (80%) patients achieved ≥ CR, 1 achieved very good partial remission (VGPR), and 1 achieved a partial remission (PR), with an overall response rate (ORR) of 100%. Amongst the control group, 18 (37%) achieved ≥ CR, 5 (10%) achieved ≥ VGPR, 21 (43%) achieved ≥PR, 3 (6%) had stable disease and 1 (2%) had disease progression, with an ORR of 91.6%. There was no significant difference in the ORR between the two groups (p=0.21). At the time of last follow-up, a total of 4 (40%) patients had relapsed in the syngeneic cohort, and 31 (65%) had relapsed in the autologous cohort (p=0.15). The median progression free survival (PFS) for the syngeneic cohort was 98.6 months (95% CI from 76-118 months), while the median PFS for auto-HCT cohort was 34.5 months (95% CI from 16-52 months) (p=0.05). Median overall survival (OS) for the syngeneic and auto-HCT cohorts were not reached and 131 months, respectively (p=0.15). The PFS difference was not due to a difference in maintenance therapy after transplant, as 6 (60%) syngeneic patients and 32 (66.7%) auto-HCT (p=0.69) received maintenance therapy respectively. CONCLUSION: Our study shows that patients with multiple myeloma who underwent syngeneic-HCT had a trend to a higher CR rate and longer PFS compared to a matched cohort that underwent auto-HCT. This benefit may be related to the absence of malignant plasma cells in the syngeneic graft, and a normal donor immune system. The efficacy of syngeneic transplants needs to be assessed in a larger number of patients to provide sufficient power to detect clinically meaningful differences with autologous transplants. Table 1 Pre-transplant variables for cases and controls. Table 1. Pre-transplant variables for cases and controls. Table 2 Transplant Outcomes Table 2. Transplant Outcomes Kaplan Maier Curves for Progression Free Survival and Overall Survival. Kaplan Maier Curves for Progression Free Survival and Overall Survival. Disclosures Bashir: Takeda: Consultancy; Spectrum: Consultancy; Takeda: Research Funding; Celgene: Research Funding. Champlin:Ziopharm Oncology: Equity Ownership, Patents & Royalties; Intrexon: Equity Ownership, Patents & Royalties.

Improvement in Overall Survival With Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

2018 ◽  
Vol 36 (8) ◽  
pp. 728-734 ◽  
Author(s):  
David S. Siegel ◽  
Meletios A. Dimopoulos ◽  
Heinz Ludwig ◽  
Thierry Facon ◽  
Hartmut Goldschmidt ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Rank Test ◽  
Free Survival ◽  
Refractory Multiple Myeloma ◽  
Risk Of Death ◽  
End Point ◽  
Grade 3

Purpose In the ASPIRE study of carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide plus dexamethasone (Rd) in patients with relapsed or refractory multiple myeloma, progression-free survival was significantly improved in the carfilzomib group (hazard ratio, 0.69; two-sided P < .001). This prespecified analysis reports final overall survival (OS) data and updated safety results. Patients and Methods Adults with relapsed multiple myeloma (one to three prior lines of therapy) were eligible and randomly assigned at a one-to-one ratio to receive KRd or Rd in 28-day cycles until withdrawal of consent, disease progression, or occurrence of unacceptable toxicity. After 18 cycles, all patients received Rd only. Progression-free survival was the primary end point; OS was a key secondary end point. OS was compared between treatment arms using a stratified log-rank test. Results Median OS was 48.3 months (95% CI, 42.4 to 52.8 months) for KRd versus 40.4 months (95% CI, 33.6 to 44.4 months) for Rd (hazard ratio, 0.79; 95% CI, 0.67 to 0.95; one-sided P = .0045). In patients receiving one prior line of therapy, median OS was 11.4 months longer for KRd versus Rd; it was 6.5 months longer for KRd versus Rd among patients receiving ≥ two prior lines of therapy. Rates of treatment discontinuation because of adverse events (AEs) were 19.9% (KRd) and 21.5% (Rd). Grade ≥ 3 AE rates were 87.0% (KRd) and 83.3% (Rd). Selected grade ≥ 3 AEs of interest (grouped terms; KRd v Rd) included acute renal failure (3.8% v 3.3%), cardiac failure (4.3% v 2.1%), ischemic heart disease (3.8% v 2.3%), hypertension (6.4% v 2.3%), hematopoietic thrombocytopenia (20.2% v 14.9%), and peripheral neuropathy (2.8% v 3.1%). Conclusion KRd demonstrated a statistically significant and clinically meaningful reduction in the risk of death versus Rd, improving survival by 7.9 months. The KRd efficacy advantage is most pronounced at first relapse.

Bortezomib-Containing Regimens (BCR) for the Treatment of Non-Transplant Eligible Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1846-1846
Author(s):  
Victor H Jimenez-Zepeda ◽  
Peter Duggan ◽  
Paola Neri ◽  
Nizar J Bahlis
Keyword(s):  
Overall Survival ◽  
Research Funding ◽  
Clinical Characteristics ◽  
Progression Free Survival ◽  
Categorical Variables ◽  
Rank Test ◽  
Cancer Center ◽  
Fisher Exact Test ◽  
Free Survival ◽  
The Impact

Abstract Introduction In patients not eligible for transplant due to age and/or co-morbidities, the selection of up-front therapy needs to balance efficacy and toxicity. Recently, regimens with bortezomib, a proteasome inhibitor proven to be efficacious in myeloma, have been reported. Based on these findings, we aimed to evaluate the impact of different bortezomib combinations for the treatment of non transplant-eligible MM. Methods All- consecutive patients treated with bortezomib-containing regimens (BCR) at Tom Baker Cancer Center (TBCC) from 01/2006 to June/2015 were evaluated. Definitions of response and progression were used according to the EBMT modified criteria and a category of very good partial response (VGPR) was added. Two-sided Fisher exact test was used to test for differences between categorical variables. A p value of <0.05 was considered significant. Survival curves were constructed according to the Kaplan-Meier method and compared using the log rank test. Results 113 consecutive patients with MM received BCR. Thirty-three patients were treated with cyclophosphamide, bortezomib and dexamethasone (CyBorD), 41 with bortezomib, melphalan and prednisone (VMP) and 39 with bortezomib and dexamethasone (VD). Clinical characteristics are shown in Table 1. At the time of analysis, 20, 17 and 18 patients in the CyBorD, VMP and VD groups are still alive and 14, 33 and 30 have already progressed, respectively. ORR and VGPR rates were 93.9%/75.7%, 80%/53% and 76%/48% (p=0.001) for patients treated with CyBorD, VMP and VD, respectively. Median OS was NR for CyBorD, compared to 41months and 37 months for VMP and VD patients (p=0.6). Median PFS was 16.7 months for CyBorD compared to 17.5 months and 11 months for VMP and VD (P=0.6), respectively. The rate of treatment discontinuation and median number of cycles were: 9%, 26% and 12.8% and 6, 7.5 and 4 cycles for CyBorD, VMP and VD patients, respectively. Patients were to receive 6-9 cycles of treatment and the regimen could be continued to a maximum of 2 years at the discretion of the treating hematologist based on tolerability and response. Nine patients (27%) in the CyBorD group and 17 (41.4%) and 4 (10%) in the VMP and VD group received maintenance treatment. Median OS and PFS was longer for the group receiving maintenance (62 months vs 32 months and 23 months vs 10 months, p=0.007). In conclusion, bortezomib containing regimens are efficacious in the treatment of non-transplant eligible MM. Patients receiving maintenance appeared to exhibit longer PFS and OS. Very elderly patients should be subjected to frailty and comorbidity indexes aiming to decrease toxicity and prolong survival. Table 1. Clinical Characteristics Characteristic CyBorD, n=33 VMP, n=41 VD, n=39 Age (median) 58 58 58 GenderMaleFemale 20 (60.6%)13 (39.4%) 22 (53.6%)19 (46.4%) 26 (66.6%)13 (33.4%) Hb (g/L) 107 110 103 Calcium (µmol/L) 2.4 2.35 2.31 Creatinine (µmol/L) 115.5 103 108 B2microglobulin (µmol/L) 4.1 3.42 5.9 Albumin (g/L) 31 31 30 Stage IStage IIStage III 6 (12.1%)14 (42.4%)13 (45.5%) 9 (21.9%)19 (46.3%)13 (31.8%) 4 (10.2%)16 (41%)18 (48.8%) LDH (IU/L) 185 179 174 BMPC (%) 31 30 33.5 Heavy chain:IgGIgAFLC onlyIgDIgMBiclonal 2247000 19148000 21107010 Light chain:KappaLambdaBiclonal 16170 29120 24150 High riskStandard risk 5 (15%) 28 6 (14.6%)35 8 (20%)31 Ab: BMPC: Bone marrow plasma cells. Figure 1. Overall survival for patients receiving CyBorD, VMP and VD Figure 1. Overall survival for patients receiving CyBorD, VMP and VD Figure 2. Progression-Free survival for patients receiving CyBorD, VMP and VD Figure 2. Progression-Free survival for patients receiving CyBorD, VMP and VD Figure 3. OS for patients receiving CyBorD, VMP and VD maintenance Figure 3. OS for patients receiving CyBorD, VMP and VD maintenance Disclosures Jimenez-Zepeda: Celgene: Honoraria; Amgen: Honoraria; J&J: Honoraria. Duggan:Jansen: Honoraria; Celgene: Honoraria. Neri:Celgene: Research Funding. Bahlis:Johnson & Johnson: Speakers Bureau; Johnson & Johnson: Consultancy; Amgen: Consultancy; Johnson & Johnson: Research Funding; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau.

Sign in / Sign up

Export Citation Format

Share Document