Impact of Chromosomal Abnormalities Del(13), T(4;14), and Del(17p) and Prior Treatment on Outcomes in Patients with Relapsed or Refractory Multiple Myeloma Treated with Lenalidomide

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3685-3685 ◽  
Author(s):  
Herve Avet Loiseau ◽  
Jean Soulier ◽  
Jean-Paul Fermand ◽  
Thierry Facon ◽  
Michel Attal ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Plasma Cells ◽  
Chromosomal Abnormalities ◽  
Progression Free Survival ◽  
Median Number ◽  
Phase Iii ◽  
Free Survival ◽  
The Impact

Abstract The chromosomal abnormalities of del(13), t(4;14), and del(17p) are associated with poor progression-free survival (PFS) and shorter overall survival (OS) in newly diagnosed multiple myeloma (MM) treated with traditional chemotherapy. In patients with relapsed or refractory MM, a recent study demonstrated that lenalidomide (Revlimid®) can overcome poor prognosis conferred by del13q and t(4;14) but not del17p13 (Bahlis et al 2007). Here, we performed a retrospective analysis of medical records obtained from 49 clinical centers participating in the French Autorisation Temporaire d’Utilisation program. Patients with relapsed or refractory MM received dexamethasone 40 mg orally (days 1–4; 9–12 and 17–20 for 4 cycles, then days 1–4 beginning with cycle 5) and lenalidomide 25 mg orally on days 1–21 of a 28 day cycle. CD138-purified plasma cells were analyzed with fluorescent in-situ hybridization (FISH) for del(13), t(4;14), and del(17p) at diagnosis. Response and disease progression endpoints were evaluated using the European Group for Blood and Marrow Transplantation criteria. A multivariate analysis was performed to assess the impact of the following 7 variables on outcomes: any chromosomal change, prior bortezomib use, prior thalidomide use, prior transplant, progression on thalidomide, age, and number of lines of previous therapy. In total, 207 patients were included in the analysis; the median number of treatment cycles was 5 (range, 1–22). Most patients in the current study had received prior thalidomide (87%) or bortezomib (81%). The overall response rate (ORR) was 59%, including 7% complete response and 14% very good partial response. Median progression-free survival (PFS) and overall survival (OS) were 9.6 months and 15.1 months, respectively. These values are comparable to the recently published phase III trials (Weber et al., 2007; Dimopoulos et al., 2007), despite the higher median number of prior therapies in this analysis (5 vs. 3). Overall, 41% of patients had del(13), 14% had t(4;14) and 5% had del(17p). The ORR was significantly lower, and PFS and OS significantly shorter, in patients with del(13) compared with patients without del(13) (ORR: 43% vs. 71%, P<0.001; PFS: 5.0 months vs. 12.5 months, P<0.0001; OS: 10.4 months vs. 17.4 months, P=0.001). A similar pattern was observed in patients with t(4;14) versus patients without t(4:14) (ORR 39% vs. 62%, p=0.04; PFS 5.5 months vs. 10.6 months, p<0.01; OS 9.4 months vs. 15.4 months, p=0.005). Multivariate analysis identified hemoglobin (<10 g/dL), progression on thalidomide, and del(13) as independent predictors of reduced PFS (Table). There was a trend towards reduced PFS with prior bortezomib use and number of prior therapies. Age, sex, prior transplant, prior thalidomide use, and t(4;14) did not affect PFS. The results from the analysis indicate that del(13), progression on thalidomide, and hemoglobin levels ≥10 g/dL have a significant impact on outcomes in heavily pre-treated patients with relapsed or refractory MM. Randomized trials are needed to further assess these findings.

Retrospective study to assess the impact of hepatitis C virus infection on the prognosis and management of multiple myeloma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20001-e20001
Author(s):  
David Kaldas ◽  
Andrew Wahba ◽  
Radwa Hamdy Azab ◽  
Ehab Mostafa Elnakoury ◽  
Nagla Fawzy Abdel Karim ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Hepatitis C Virus ◽  
Retrospective Study ◽  
Hepatitis C ◽  
Progression Free Survival ◽  
Hcv Infection ◽  
Cytotoxic Agents ◽  
Free Survival ◽  
The Impact

e20001 Background: Multiple Myeloma (MM) is a neoplasm of the post-germinal center, terminally differentiated B-cells. MM accounts for 1% of all types of cancer and 10% for all hematologic malignancies. Chronic hepatitis C virus (HCV) is an infection that affects over 71 million patients worldwide. Cytotoxic agents and immunosuppressive therapy as steroids are the main line of therapy in lymphoid malignancies, but these drugs may exacerbate chronic viral hepatitis and cause uncontrolled replication of hepatitis viruses. The impact of HCV infection on MM patients remains unclear. Objective: To assess the impact of HCV infection on the prognosis and management of MM patients. Methods: A 10-year retrospective study of MM patients was conducted at Cairo University Clinical Oncology Department from January 2009 to April 2019. Results: During this time, 150 patients were diagnosed with MM, 109 (72.7%) were HCV negative, 24 (16%) were HCV positive, and 17 (11.3%) with unknown HCV status. The median age was 51 and 54 years for HCV negative and positive groups respectively, with a statistically insignificant difference (p-value > 0.2). In the multivariate analysis, HCV infection was not an independent factor related to overall survival (OS), however age, creatinine and hemoglobin levels correlated significantly with OS (p < 0.009, 0.008, 0.031 respectively). The median OS for the HCV negative group was 31.11 months (95% CI: 22.62 - 39.61) compared to 37.66 months (95% CI: 7.19 - 68.13) for the HCV positive group. The median progression-free survival (PFS) for all patients was 18.9 months, for HCV positive patients was 15.36 months (95% CI: 13.18 – 17.54), and for HCV negative patients was 20.49 months (95% CI: 14.13 – 26.85). Age below 60 years and creatinine level less than 2 mg/dL were statistically significant for favorable disease-free survival (DFS) (p < 0.030, 0.034 respectively). Conclusions: Age, creatinine and hemoglobin levels are significant prognostic factors in MM but HCV status doesn’t affect the overall survival or progression-free survival. HCV infection should not contraindicate MM therapy.

Monoclonal and Oligoclonal Bands After Single Autologous Stem Cell Transplantation in Patients with Multiple Myeloma: Impact On Overall Survival and Progression-Free Survival

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 595-595
Author(s):  
Victor Hugo Jimenez-Zepeda ◽  
Norman Franke ◽  
Andrew Winter ◽  
Suzanne Trudel ◽  
Christine I. Chen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Prognostic Factor ◽  
Light Chain ◽  
Progression Free Survival ◽  
Oligoclonal Bands ◽  
Cell Transplant ◽  
Free Survival

Abstract Abstract 595 Multiple myeloma is a malignancy of terminally differentiated plasma cells in which the malignant plasma cell clone usually produces a single abnormal unique monoclonal antibody with a constant isotype and light chain-restricted paraprotein. Recently, the occurrence of oligoclonal and monoclonal bands (OB/MB) not related to the original clone has been reported in patients with multiple myeloma who undergo autologous stem cell transplant (ASCT) and/or receive treatment with novel agents. Based on this data, the aim of our study was to assess the impact of monoclonal (MB) and oligoclonal bands (OB) occurrence on overall survival (OS) and progression-free survival (PFS) for MM patients undergoing single ASCT at Princess Margaret Hospital (PMH). Patient and Methods: All consecutive patients with documented MM undergoing single ASCT at PMH from 01/00 to 12/07 were evaluated. Oligoclonal banding (OB) was defined as the development of two or more concurrent monoclonal-type bands on the serum electrophoretic pattern, with either a different heavy or light chain component from the original M-protein band at day+100 post-ASCT. A new monoclonal band (MB) was defined as a heavy and/or light chain immunoglobulin distinct from the initially diagnosed MM. All cases with OB/MB in our series fulfilled the criteria of secondary monoclonal gammopathy of undetermined significance (MGUS). Multivariate analysis was performed with the Cox proportional hazard model. All analyses were performed using the SPSS 13.0 software. Results: Between January 2000 and December 2007, 788 patients were identified. Clinical and laboratory characteristics are listed in Table 1 Ninety-six patients (12.1%) developed OB/MB at 3 months from ASCT: 32 patients (33.3%) had OB, and 64 patients (66.7%) had a new MB. The median duration of the OB/MB was 12 months (range 4–52 months). OB and MB emerged after ASCT in 14% (60/409) of patients receiving VAD, 7.0% of patients receiving bortezomib (6/86) and 8.6% of patients receiving thalidomide (6/69) containing regimens as induction therapy. Thirty-seven (38%) patients with subsequent development of an OB/MB had achieved ≥VGPR after induction and this rate improved to 79% (76/96) at day +100 post-ASCT. Patients who did not develop OB/MB had a ≥VGPR rate of 28% and 58% after induction and day+100 post-ASCT, representing a lower rate than patients with OB/MB (p=0.07 and 0.002, respectively). At the time of this analysis, 65 (67.7%) of the cohort patients who developed OB/MB are alive and 68 have already progressed (70.8%). Median overall survival for patients who did not develop OB/MB at day+100 post ASCT was 74.5 months compared to 115.5 months for those who developed OB/MB (p=0.0098). Multivariate analysis shows developing of OB/MB as an independent prognostic factor for OS and PFS (p=0.006 and 0.021, respectively). (Fig1a-b) The duration of the OB/MB did not affect OS and PFS. In conclusion, OB/MB occurrence is an important prognostic factor in MM patients who undergo ASCT, the biological significance and its impact on clinical outcomes should be prospectively validated. Disclosures: Chen: Roche: Honoraria; Johnson & Johnson, Lundbeck, Celgene: Consultancy; Johnson & Johnson, Celgene, GlaxoSmithKline: Research Funding. Tiedemann:Janssen: Honoraria; Celgene: Honoraria. Kukreti:Roche: Honoraria.

scholarly journals Exosome-Transmitted PSMA3 and PSMA3-AS1 Promotes Proteasome Inhibitors Resistance in Multiple Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4434-4434
Author(s):  
Wenzhuo Zhuang ◽  
Sha Song ◽  
Huiying Han ◽  
Gao Fan ◽  
Nengjun Yi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Clinical Response ◽  
Univariate Analysis ◽  
Proteasome Inhibitors ◽  
Progression Free Survival ◽  
Mrna Levels ◽  
Free Survival ◽  
Myeloma Cells

Abstract PIs resistance is a major challenge for multiple myeloma (MM). The bone marrow microenvironment facilitates crucial interactions between the myeloma cells and mesenchymal stem cells (MSCs) that permit MM to survive and proliferate progression. Exosomes are involved in intercellular communication, and in this study we investigated how the transfer of exosomic PMSA3 (encodes proteasome subunit α7) and lncPSMA3-AS1 from MSCs to MM cells affected proteasome inhibitors resistance (Figure 1). We firstly underscored that exosomes derived from r-MSCs (MSCs derived from bortezomib-resistant patients), but not from s-MSCs (MSCs derived from bortezomib-resistant patients) reduced the proteasome inhibitors sensitivity in MM cells (Figure 2). To further elucidate mechanisms of Proteasome inhibitors (PIs) resistance, we retrieved a database containing gene expression profile of 169 myeloma cases with clinical response and disease prognosis (GSE9782). The analysis of this dataset showed that the mRNA levels of PSMA3 and PSMA3-AS1 in CD138+ cells are upregulated in bortezomib-resistant patients (Figure 3A-3D). Moreover, Kaplan-Meier analysis showed that high PSMA3 levels in CD138+ MM cells were correlated with reduced progression-free survival (PFS) (p = 0.0307) and overall survival (OS) (p = 0.0328) (Figure 3E). Cox proportional hazards regression analysis further demonstrated that high PSMA3 was an independent prognostic factor for MM patients with bortezomib therapy in a multivariate analysis (p = 0.0013, HR = 1.3104, 95%CI = 1.1113-1.545). Further analysis of Oncomine data showed that the PSMA3 levels appeared a progressive increase in MGUS, SM, MM and PCL (Figure 3F-3H). Similarly, our PIs resistant models (U266BR, U266CR, U266IR, MM.1SBR, MM.1SCR, MM.1SIR) consistently displayed up-regulation of PSMA3 and PSMA3-AS1 expression (Figure 3J). Consistent with this previously published study, our clinical data showed that the mRNA levels of PSMA3 and PSMA3-AS1 are upregulated in CD138+ MM cells derived from bortezomib resistant patients relative to those from bortezomib sensitive patients (Figure 3I). In addition, r-MSCs had increased expression of PSMA3 and PSMA3-AS1 compared to s-MSCs (Figure 3K). Moreover, the expression of PSMA3 and PSMA3-AS1 in MSCs were positively correlated with that in CD138+ myeloma cells (Figure 3L). These data suggested that high levels of PSMA3 and PSMA3-AS1 were correlated with proteasome inhibitors resistance in MM. We further identified that PSMA3 and PSMA3-AS1 in MSCs could be incorporated into exosomes and transmitted to myeloma cells, thus promoting PIs resistance (Figure not shown). PSMA3-AS1 was capable of forming an RNA duplex with PSMA3 pre-mRNA at overlapping regions and this duplex transcriptionally promoted PSMA3 expression by increasing its stability, conferring bortezomib resistance to myeloma cells (Figure not shown). To evaluate the therapeutic potential of PSMA3-AS1 in MM in vivo, bioluminescent MM models (U266-luc), which recapitulates the clinical sequelae, anatomic distribution of MM lesions, and hallmark bone pathophysiology observed in MM patients were established. Intravenously administered siPSMA3-AS1 was found to be effective in increasing bortezomib sensitive (Figure 4). Moreover, circulating exosomal PSMA3 and PSMA3-AS1 derived from the plasma of MM patients were significantly associated with both progression-free survival (PFS) and overall survival (OS) in the univariate analysis, and were still statistically significant after adjusting for the international staging system (ISS) and several other clinical variables in the multivariate analysis (Figure not shown). In summary, our results indicated a unique role of exosomic lncPSMA3-AS1 in transferring proteasome inhibitors resistance from MSCs to MM cells, through a novel exosomic lncPSMA3-AS1/PSMA3 signaling pathway. Exosomic PSMA3 and PSMA3-AS1 may serve as a potential therapeutic target for proteasome inhibitors resistance and a prognostic predictor for clinical response. Disclosures No relevant conflicts of interest to declare.

Daratumumab, pomalidomide, and dexamethasone in relapsed refractory multiple myeloma (RRMM): A comparison with contemporary clinical trials.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20011-e20011
Author(s):  
Barry Paul ◽  
Myra M. Robinson ◽  
Jordan Robinson ◽  
Ami Ndiaye ◽  
Manisha Bhutani ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Plasma Cells ◽  
Progression Free Survival ◽  
Median Number ◽  
Phase Iii ◽  
Published Data ◽  
Refractory Multiple Myeloma ◽  
Overall Response ◽  
Previously Treated

e20011 Background: Multiple Myeloma (MM) is an incurable malignancy of terminally differentiated plasma cells. The combination of pomalidomide/dexamethasone with either daratumumab or isatuximab is FDA approved for relapsed refractory multiple myeloma (RRMM) based on randomized phase III trial data. Herein, we compare our center’s experience with published data to help identify the most appropriate patient population for this regimen outside of the context of clinical trials. Methods: We interrogated our internal plasma cell disorder database to identify all patients with RRMM at our institution who were treated with the combination of daratumumab, pomalidomide, and dexamethasone (Dara-Pd). We evaluated the best response achieved, overall response rate (ORR), progression free survival (PFS), and overall survival (OS) measured from initiation on Dara-Pd. Kaplan Meier methods were used to estimate PFS and OS curves. Fisher’s exact tests and log rank tests were used to determine the association between outcomes and variables of interest. Results: Between Dec 2015 and Dec 2020, 98 patients were identified, of which 97 were evaluable for response. Median number of prior lines of therapy was 2 (range 1-12), with 23 patients (23%) previously treated with 3 prior lines and 24 patients (25%) previously treated with ≥4 lines of therapy. Most patients were refractory to an IMiD (79.6%), a PI (65.3%), or both (56.1%). The ORR was 69.1%, > VGPR rate was 33%. ORR was significantly improved for patients who received Dara-Pd after 1 line (p = 0.03), but depth of response (≥VGPR), was similar (p = 0.62). At a median follow up of 10.8 months, 1-year PFS was 76.6% in patients after 1 line, 38.8% in patients after 2-3 lines, and 35% in patients after > 4 lines. Overall response rates appear comparable to published phase III trials comparing the combination of Pd with or without an anti-CD38 monoclonal antibody (Table 1). While PFS was somewhat lower in our population, subset analysis showed that PFS was significantly lower in patients who were PI refractory (10.8 months vs 6 months; p = 0.014), and in patients who were both IMiD and PI refractory (20.4 months vs 6 months p = 0.01), but OS was similar in these populations. Conclusions: Our data suggests that the combination of Dara-Pd has activity in heavily pretreated patients, including patients who are both IMiD and PI refractory and remains a viable option for these patients outside the context of a clinical trial.[Table: see text]

Arsenic Trioxide with Ascorbic Acid and High-Dose Melphalan: A New Preparative Regimen for Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1159-1159 ◽  
Author(s):  
Muzaffar H. Qazilbash ◽  
Marilyn S. Davis ◽  
Aleman Ana ◽  
Linda Roden ◽  
Floralyn Libunao ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Ascorbic Acid ◽  
Arsenic Trioxide ◽  
Survival Probability ◽  
Progression Free Survival ◽  
High Dose ◽  
Free Survival ◽  
Kaplan Meier ◽  
The Impact

Abstract Backround: Arsenic trioxide (ATO), an active agent against multiple myeloma, has been shown to be synergistic with melphalan both in vitro and in vivo. We conducted a phase I/II trial to determine the safety and efficacy of a combination of arsenic trioxide, melphalan and ascorbic acid (AA) as prepaprative regimen in patients undergoing high-dose therapy (HDT) and autologous hematopoietic progenitor cell transplantation (AHPCT) for multiple myeloma (MM). We also assessed the impact ATO levels on melphalan pharmacokinetics (PK), engraftment and toxicity. Methods: Twenty-five patients with secretory myeloma (11 females, 14 males median age: 53, range: 49 – 69) were treated b/w 4/04 and 1/05. All patient received melphalan 100 mg/m2 IV on days -4 and -3 and AA 1000 mg/day IV on days −9 to −3. Patients were randomized to 3 arms; no ATO (arm 1), ATO 0.15 mg/kg IV on days −9 to −3 (arm 2) and ATO 0.25 mg/kg IV on days −9 to −3 (arm 3). Seven patients had a prior autograft. Median CD34 cells dose infused was 4.4 x 106/kg (range 2.3–10.9). Results: Patients were evenly matched except for a high median β2m level (3.6 vs. 2.4 in arms 1 and 2, p=0.04) in arm 3. With a median F/U of 7.1 months post autograft, no dose-limiting toxicity or non-relapse mortality was seen. Median ATO level on day 0 in arms 1, 2 and 3 were 0.2, 26.3 and 46.2 ng/ml, respectively. Toxicity was limited grade I or II nausea, vomitting and diarrhea. Median time to neutrophil engraftment (ANC &gt;500/dl) was 9 days. There were no engraftment failures or delays in the ATO arms. Response rates (RR) are shown in Table 1. With a median F/U of 7.1 months (range, 6.4 – 8.9 months), the progression-free survival (PFS) and overall survival (OS) are as shown in Figure 1. There was no significant difference in RR, PFS or OS between the 3 arms. Melphalan PK was not altered by ATO pretreatment. Conclusions: Arsenic trioxide, given in combination with melphalan and ascorbic acid as preparative regimen, is safe and well tolerated. A longer follow up is needed to determine the impact of this combination on survival. Response Rate at 3-Month Evaluation Response at 3 months CR PR MR SD PD p = 0.55 CR = complete response, PR = partial response, MR = minimal response, SD = stable disease, PD = progressive disease Arm 1 (no ATO) 1 5 0 1 1 Arm 2 (ATO 0.15) 1 5 2 0 1 Arm 3 (ATO 0.25) 0 7 0 0 0 Figure 1. The Kaplan-Meier estimates for progression-free survival probability (N=25). Figure 1. The Kaplan-Meier estimates for progression-free survival probability (N=25). Figure 2. The Kaplan-Meier estimates for overall survival probability (N=25). Figure 2. The Kaplan-Meier estimates for overall survival probability (N=25).

Impact of the prior chemotherapy with two different fluoropyrimidines on the efficacy of CapeIRI or FOLFIRI in metastatic colorectal cancer: An exploratory analysis of the phase III AXEPT trial.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 711-711
Author(s):  
Tae Won Kim ◽  
Kei Muro ◽  
Rui-hua Xu ◽  
Young Suk Park ◽  
Wei Wang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Progression Free Survival ◽  
Exploratory Analysis ◽  
Phase Iii ◽  
Free Survival ◽  
Prior Chemotherapy ◽  
Oral Fluoropyrimidine ◽  
Significant Difference ◽  
Phase Iii Study ◽  
The Impact

711 Background: Modified CapeIRI (irinotecan 200 mg/m2 on day 1, capecitabine 1600 mg/m2 on days 1–14 every 3 weeks) with or without bevacizumab (± BV) has shown non-inferiority of overall survival compared with FOLFIRI ± BV based on the phase III study, AXEPT, as second-line chemotherapy for patients with mCRC. In this exploratory analysis of the AXEPT trial, we evaluated the impact of the prior chemotherapy with two different fluoropyrimidine backbones (fluorouracil and leucovorin vs oral fluoropyrimidine) on the efficacy of CapeIRI and FOLFIRI. Methods: Patients were randomized to receive standard FOLFIRI ± bevacizumab or modified CapeIRI ± bevacizumab after failure to fluoropyrimidine-based chemotherapy in the AXEPT study. Prior fluoropyrimidine backbones were categorized into oral fluoropyrimidine-based (eg, capecitabine or S-1) regimen (oral 5-FU group) and fluorouracil and leucovorin-based regimen (infusional 5-FU group). Assessed endpoints included overall survival, progression-free survival, response rate, and safety. Results: Prior fluoropyrimidine backbone was available for 642 patients among all 650 randomized patients (oral 5-FU group in 291, and infusional 5-FU group in 351). Median overall survival was 17.0 and 16.7 months for FOLFIRI ± BV and CapeIRI ± BV in the prior oral 5-FU group, and 14.9 and 16.7 months for FOLFIRI ± BV and CapeIRI ± BV in the prior infusional 5-FU group. Median progression-free survival was 7.9 and 8.6 months for FOLFIRI ± BV and CapeIRI ± BV in the prior oral 5-FU group, and 6.8 and 8.3 months for FOLFIRI ± BV and CapeIRI ± BV in the prior infusional 5-FU group. Conclusions: There was no significant difference in the efficacy of CapeIRI or FOLFIRI regardless of prior fluoropyrimidine backbones. Therefore, CapeIRI ± BV could also be effective for patients after failure of oral fluoropyrimidine-based chemotherapy (eg, CapeOX ± BV). Clinical trial information: NCT01996306. [Table: see text]

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.

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.

Inflammatory indexes neutrophils/lymphocytes, platelets/lymphocytes and red-cell distribution width (RDW) as prognostic biomarkers in advanced solitary fibrous tumors (SFT) treated with pazopanib: Correlative study of GEIS-32 trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11511-11511
Author(s):  
Javier Martin Broto ◽  
Samuel Hidalgo ◽  
David Silva Moura ◽  
Silvia Stacchiotti ◽  
Antonio Lopez-Pousa ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Complete Blood Count ◽  
Progression Free Survival ◽  
Statistical Correlation ◽  
Phase Iii ◽  
Pivotal Phase ◽  
Distribution Width ◽  
Best Response ◽  
The Impact

11511 Background: Pazopanib (P) was assessed prospectively in a phase 2 study in SFT resulting in a longer progression free survival (PFS) and overall survival (OS) compared to historical controls treated with chemotherapy. No statistical correlation was found between angiogenic factors and P in its pivotal phase III sarcoma trial. In the last two years, a soaring interest on the prognostic and predictive value of inflammatory indexes such as neutrophil/lymphocyte (NLR) and platelet/lymphocyte (PLR) is emerging in sarcomas. A retrospective analysis of inflammatory indexes of patients who entered the GEIS-32 (NCT02066285) trial was performed. In that trial advanced SFT patients were treated with P from front-line. Methods: All eligible patients who entered in the typical- and malignant-SFT cohort of the GEIS-32 trial were included in this analysis. To determine NLR and PLR, baseline values of platelets (10e9/L), neutrophils (10e9/L) and lymphocytes (10e9/L) were obtained from complete blood count tests. Additionally, RDW (standardized as 1 = upper value of normal range) values at baseline were also determined. The impact of NLR, PLR and RDW on OS, PFS and Choi response were analyzed by univariate and multivariate analysis. MAXSTAT was used to determine optimal cut-off points for overall survival. Metastasis free interval (MFI), mitotic count and ECOG were also analyzed, among others. Results: Sixty-seven out of 70 enrolled SFT patients, median age 63-y and 57% female, were considered for this analysis. The median follow-up from treatment initiation was 20.0 months. High standardized RDW value at baseline (cut-off 1.03) was significantly associated with worse OS [10.7 months (95% CI 3.8-17.5) vs 49.8 months (95% CI 9.4-90.2), p < 0.001] and worse PFS [8.8 months (95% CI 0.9-7.0) vs 9.8 months (7.4-12.3), p = 0.001]. High PLR (cut-off 242) significantly correlated with worse OS [10.7 months (95% CI 5.2-16.2) vs 49.8 months (95% CI 14.6-85.0), p < 0.001] and worse PFS [4.5 months (95% CI 2.0-7.0) vs 10.1 months (95% CI 6.3-13.9), p = 0.005], and high NLR (cut-off 3.78) was significantly associated with worse OS [11.7 months (95% CI 3.5-19.8) vs NA, p < 0.001] and worse PFS [4.5 months (95% CI 1.9-7.0) vs 10.8 months (95% CI 8.7-12.9), p = 0.010]. Independent variables in multivariate analysis were NLR, RDW, MFI and mitosis for PFS; while RDW and ECOG for OS (see table). Further, NLR and mitosis were independent factors for Choi progressive disease (as best response). Conclusions: High NLR and RDW values were independent biomarkers of worse outcome in advanced SFT patients treated with pazopanib.[Table: see text]

Purging of Autologous Peripheral-Blood Stem Cells Using CD34 Selection Does Not Improve Overall or Progression-Free Survival After High-Dose Chemotherapy for Multiple Myeloma: Results of a Multicenter Randomized Controlled Trial

2001 ◽  
Vol 19 (17) ◽  
pp. 3771-3779 ◽  
Author(s):  
A. Keith Stewart ◽  
Robert Vescio ◽  
Gary Schiller ◽  
Oscar Ballester ◽  
Stephen Noga ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Peripheral Blood ◽  
Plasma Cells ◽  
High Dose Chemotherapy ◽  
Phase Iii ◽  
High Dose ◽  
Free Survival ◽  
Disease Free ◽  
Cd34 Selection

PURPOSE: Although high-dose chemotherapy supported by autologous peripheral-blood progenitor-cell (PBPC) transplantation improves response rates and survival for patients with multiple myeloma, all patients eventually develop progressive disease after transplantation. It has been hypothesized that depletion of malignant plasma cells from autografts may improve outcome by reducing infused cells contributing to relapse. PATIENTS AND METHODS: A randomized phase III study using the CEPRATE SC System (Cellpro, Bothell, WA) to enrich CD34+ autograft cells and passively purge malignant plasma cells was completed in 190 myeloma patients randomized to receive an autograft of CD34-selected or unselected PBPCs. RESULTS: After CD34 selection, tumor burden was reduced by 1.6 to 6.0 logs (median, 3.1), with 54% of CD34-enriched products having no detectable tumor. Median time to count recovery, number of transfusions, transplantation-related mortality, and days in hospital were equivalent between the two transplantation arms. With a median follow-up of 37 months, 33 patients (36%) in the selected and 34 patients (35%) in the unselected arm had died (P = .784). Median overall survival in the selected arm was reached at 50 months and is not reached at this time in the unselected arm (P = .78). Median disease-free survival was 100 versus 104 weeks (P = .82), with 67% of patients in the selected arm and 66% of patients in the unselected arm relapsing. CONCLUSION: This phase III trial demonstrates that although CD34 selection significantly reduces myeloma cell contamination in PBPC collections, no improvement in disease-free or overall survival was achieved.

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