Combination of Adoptive Cellular Immunotherapy and Bortezomib-Based Regimens Increase the Progression Free Survival of the Patients with Multiple Myeloma

Abstract Objective: In our previous studies show that bortezomib can enhance the sensitivity of multiple myeloma (MM) cells to the cytotoxity of γδT, nature killer (NK) cells and cytokine-induced killer (CIK) cells, and there is synergistic effect among these three types of cells as well. Therefore, the efficacy and safety of combination of adoptive cellular immunotherapy (ACI) with NK, γδT and CIK cells and bortezomib-based chemotherapy was investigated in this study. Method: 27 patients were recruited in this study with newly-diagnosed MM and received Bortezomib-based therapy during September 2008 and September 2013 in the First Hospital of Jilin University. The patients were divided into study group (ACI plus bortezomib-based therapy) and control group (bortezomib-based therapy alone). There are 14 patients in study group with median age of 60.5 (54-73) years old, while 13 patients in control group with median age of 56 (41-80) years old. In the study group, autologous peripheral blood mononuclear cells (PBMCs) were collected from the peripheral blood by apheresis at the first day, and were induced into NK, γδT and CIK cells, then the expanded immunocytes were infused back to the patients after 14 days culture ex vivo. The number of cells for each transfusion ranged from 1.2×109- 2.0×109 cells. Progression-free survival (PFS) and adverse effects were investigated. One course of ACI would be done within 3 weeks and contain six times of infusion in total. This study was approved by the Ethical Committee of the First Hospital of Jilin University. Written informed consent was obtained from all patients before their enrollment into the study. Result:In this study, the percentage of CIK (CD56+CD3+), NK (CD56+CD3-) and γδT (Vγ9+) before and after induction were 4.39% (1.5%-8%) vs 46.32% (27%-50%), 10.35% (5.1%-12.6%) vs 95.28% (70.1%-99.6%), 4.72% (2.61%-11.2%) vs 90.64% (60.5%-97.9%), respectively. The median follow-up time was 18 months. The characteristics including age, gender, stage, chemotherapy regimen etc. had no significant difference between the two groups. The median PFS in study group was 24.5m (12-48), and the median PFS was 12m (5-32) in control group (P=0.018). For subgroup analysis, the median PFS in the study group receiving >3 courses and ≦3 courses group were 36m (24-48) and 20m (12-36), respectively (P=0.141). Among the patients receiving ACI, one patient felt mild fatigue after infusion. One patient had transient fever after one infusion (38 °C) and recovered 1 h later. No other significant side effects were observed. Conclusion: Combination of NK, γδT and CIK cells based ACI and bortezomib-based chemotherapy is well tolerated and shows a great potential to improve the PFS of the patients with MM. This study provided a novel strategy for the treatment of MM, and it is worthwhile to study this combination strategy in multi-center randomized clinical trials. Disclosures No relevant conflicts of interest to declare.

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Lenalidomide and Low Dose Dexamethasone Plus Elotuzumab or Carfilzomib for Relapsed or Refractory Multiple Myeloma: A Comparison of Progression-Free Survival with Reconstructed Individual Participant Data

BioMed Research International ◽

10.1155/2018/9057823 ◽

2018 ◽

Vol 2018 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Shuo Li ◽

Xiang-Yu Meng ◽

Souraka Tapara Dramani Maman ◽

Yong-Nong Xiao ◽

Sheng Li

Keyword(s):

Multiple Myeloma ◽

Survival Analysis ◽

Low Dose ◽

Progression Free Survival ◽

Disease Stage ◽

Free Survival ◽

Kaplan Meier ◽

Significant Difference ◽

Baseline Status ◽

Individual Participant

Background. Refractory and relapsed multiple myeloma (RRMM) remains a clinical challenge. We compared the progression-free survival (PFS) of RRMM patients treated with lenalidomide and low dose dexamethasone plus elotuzumab or carfilzomib (ELD vs. CLD), using reconstructed individual patient data (IPD) based on two published trials reports. Methods. We extracted data of study-level characteristics from original trial reports. We evaluated the comparability between the two treatment groups in terms of baseline status. Digitization of PFS Kaplan-Meier curves, reconstruction of IPD data, and subsequent survival analysis were performed. Distribution of progression and death events over time was visualized as histograms and corresponding kernel density lines, and Kaplan-Meier survival curves were plotted. Hazard ratio (HR) and corresponding 95% confidence interval (95% CI) were calculated. Results. Significant difference in race and disease stage distribution was found (P < 0.0001). Higher proportion of white patients and patients with advanced disease in the carfilzomib group was identified. Survival analysis revealed better PFS in the carfilzomib group (elotuzumab group vs. carfilzomib group: HR = 1.36, 95% CI = [1.11-1.67]). Conclusion. The CLD regimen may result in better PFS as compared with the ELD regimen in RRMM patients.

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Efficacy of Daratumumab Based Regimens Compared to Standard of Care for Transplant Ineligible Newly Diagnosed Multiple Myeloma in Phase III Clinical Trials: A Meta-Analysis

Blood ◽

10.1182/blood-2020-137141 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 32-33

Author(s):

Zahoor Ahmed ◽

Karun Neupane ◽

Rabia Ashraf ◽

Amna Khan ◽

Moazzam Shahzad ◽

...

Keyword(s):

Multiple Myeloma ◽

Clinical Trials ◽

Standard Care ◽

Progression Free Survival ◽

Phase Iii ◽

Control Group ◽

Two Phase ◽

Phase Iii Trial ◽

Free Survival ◽

Phase Iii Clinical Trials

Introduction: Daratumumab (Dara) is a human anti-CD38 monoclonal antibody approved for multiple myeloma (MM) treatment. Dara has a promising efficacy and a favorable safety profile in newly diagnosed MM (NDMM) patients. This study is focused on the efficacy and safety of Dara when added to the standard care regimen in transplant ineligible NDMM in phase III clinical trials. Methods: We performed a comprehensive database search on four major databases (PubMed, Embase, Cochrane, and Clinicaltrials.gov). Our search strategy included MeSH (Medical Subject Headings) terms and key words for multiple myeloma and Dara including trade names and generic names from date of inception to May 2020. Initial search revealed 587 articles. After excluding review articles, duplicates, and non-relevant articles, two phase III clinical trials were included which reported overall response rate (ORR), and progression free survival (PFS) of transplant ineligible NDMM patients with Dara addition to standard care regimen. Odds ratios (OR) of ORR were computed and hazard ratios (HR) of PFS (along with 95% confidence intervals; CI) were extracted to compute a pooled HR using a fixed effect model in RevMan v.5.4. Results: A total of 1453 transplant ineligible NDMM patients were enrolled and evaluated in two phase III randomized clinical trials. Seven hundred and eighteen patients were in Dara group and 735 patients were in control group. Bahlis et al. (2019) studied Dara + lenolidamide (R) and dexamethasone (d) vs Rd in NDMM pts (n=737) in MAIA phase III trial. Similarly, Mateos et al. (2018) reported the role of Dara + bortezomib (V) + melphalan (M), and prednisone (P) vs VMP in NDMM pts (n=706) in a phase III trial (Alcyone). A pooled analysis of these phase III trials showed ORR (OR: 3.26, 95% CI 2.36-4.49; p < 0.00001, I2 = 0%), and progression free survival (PFS) (HR: 0.53, 95% CI 0.43-0.65; p < 0.00001, I2 = 0%). Achievement of minimal residual disease (MRD) negative status was significant in Dara based regimen as compared to control group (OR: 4.49, 95% CI 3.31-6.37; p < 0.00001, I2 = 0%). Dara addition to standard care regimen (Rd and VMP) decreased the risk of progression/death to 42% (HR: 0.58, 95% CI 0.48-0.70; p < 0.00001, I2 = 0%). The addition of Dara increased the risk of neutropenia (OR: 1.41, 95% CI 1.07-1.85; p < 0.02, I2 = 44%), and pneumonia (OR: 2.25, 95% CI 1.54-3.29; p < 0.0001, I2 = 37%) vs control group. However, decreased risk of anemia (OR: 0.64, 95% CI 0.49-0.85: p < 0.002, I2=30%) was observed in Dara group vs control group (Figure 1). Conclusion: Addition of Dara to the standard care regimen for transplant ineligible NDMM achieved the surrogate end points with improved efficacy and MRD negative status with manageable toxicity. However, data from more randomized controlled trials is needed. Table Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

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Immunologic Recovery after Autologous Transplant in Multiple Myeloma and Progression Free Survival

Blood ◽

10.1182/blood.v112.11.4444.4444 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4444-4444

Author(s):

Fernanda Maria Rodrigues Trigo-Miranda ◽

Rui Cordeiro Bergantim ◽

Ricardo Moreira Pinto ◽

Patricia Guimarães ◽

Jose E. Guimaraes

Keyword(s):

Multiple Myeloma ◽

Progression Free Survival ◽

Response To Treatment ◽

Cell Transplant ◽

Haematopoietic Progenitor Cell ◽

Free Survival ◽

Post Transplant ◽

Historical Comparison ◽

Significant Difference

Abstract Several factors influencing disease progression and survival have been identified in multiple myeloma (MM). We analysed a series of 49 consecutive patients with MM that underwent autologous haematopoietic progenitor cell transplant (HPCT) in one center regarding the following variables: use of G-CSF for haematopoietic recovery post-transplant; recovery of normal IgM levels at day +100 post-transplant; levels of lymphocytes namely of the CD4+ and CD8+ subsets also at day +100. Before 2006, all patients had G-CSF starting 24 hours after the cell infusion until neutrophil > 500×10^9/L in two consecutive days; in the years 2006–2008, no G-CSF was given to transplanted patients. A historical comparison was done and at the time of this study no significant difference in progression free survival (Kaplan-Meyer analysis), was detected between the two groups, possibly due to the shorter follow-up of the “no G-CSF” (n=19) group; nevertheless median progression free survival (PFS) in the “G-CSF” group was 12 months while median PFS was not attained in the “no G-CSF” group (median follow-up = 7 months). Post transplant IgM levels were also determined in 39 patients. Eighteen patients recovered normal IgM levels at day +100 (46.8 %) and 21 (53.8 %) did not. Comparison of Kaplan-Meyer curves for the two groups did not show any statistically significant difference but there is a sharp difference between median PFS of the “low IgM” (10 months) and the “normal IgM” (27 months) groups. CD4/CD8 ratio was determined in 18 patients at day +100. The ratio varied between 0 and 0.63 (median – 0.305). No correlation was found between post-transplant IgM recovery and CD4/CD8 ratio. In conclusion, in our series of MM patients treated with autologous HPCT we could not find a definite relationship between immunologic recovery and response to treatment although there is a trend to a better outlook of the patients which recover normal IgM levels. It is also uncertain whether use of G-CSF in the post-transplant period would have any effect on disease behaviour.

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Unmanipulated Haploidentical Allogeneic Hematopoietic Cell Transplantation for Multiple Myeloma Using Post Transplant Cyclophosphamide Anti-Gvhd Prophylaxis

Blood ◽

10.1182/blood.v128.22.3475.3475 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3475-3475 ◽

Cited By ~ 1

Author(s):

Luca Castagna ◽

Alberto Mussetti ◽

Raynier Devillier ◽

Alida Dominietto ◽

Magda Marcatti ◽

...

Keyword(s):

Multiple Myeloma ◽

Peripheral Blood ◽

Acute Gvhd ◽

Hematopoietic Cell Transplantation ◽

Chronic Gvhd ◽

Progression Free Survival ◽

Free Survival ◽

Post Transplant ◽

Kaplan Meier ◽

Gvhd Prophylaxis

Abstract Backgrounds: Allogeneic Hematopoietic Cell Transplantation (HCT) is a potentially curative treatment for fit patients with relapsed/refractory multiple myeloma (MM). When a HLA-identical donor is not available, haploidentical HCT (haploHCT) represents an acceptable therapeutic option, especially when post-transplant cyclophosphamide (PT-Cy) is used as anti-GVHD prophylaxis. Patients and methods: Twenty-nine patients (median age 56 years, range 47-70) undergoing myeloablative (n=15) or reduced-intensity (n=14) haploHCT from February 2011 to November 2015 are included in this retrospective analysis. The median number of previous lines of therapy was 2 (range 1-7) with 27 (93%) of patients having previously performed an autologous HCT. Both bortezomib and lenalidomide were used in 27 (92%) patients before haploHCT. Eighteen patients (62%) had chemosensitive disease at time of haploHCT (CR=4, VGPR=9, PR=5) and 11 (38%) had chemorefractory disease (PD=7, SD=4). Graft source was marrow-derived in 59% (n=17) and peripheral blood in 41% (n=12) of patients. Standard post-transplant cyclophosphamide anti-GVHD prophylaxis (50mg/mq day +3 and +4 or +5) plus mycophenolate and cyclosporine (n=24) or tacrolimus (n=3) or rapamycine (n=2) was used for the whole study cohort. Overall survival (OS) and Progression Free Survival (PFS) were performed with Kaplan-Meier analysis. Neutrophil and platelets engraftment, acute GVHD, chronic GVHD, Non-Relapse-Mortality (NRM) and Relapse Incidence/Progression of Disease (RI/POD) were obtained with competing risk analysis. Results: At day +30, neutrophil and platelets engraftments were 86% (95%CI:65-95) and 59% (95%CI:38-74), respectively. Acute GVHD grade >2 at days +100 and +180 were 38% (95%CI: 20-55%) and 41% (95%CI: 23-59%), respectively. All grade chronic GVHD at 12 and 18 months was 21% (95%CI: 8-37. At 18 months, RI/POD was 39% (95%CI:20-58%) and NRM 15% (CI95%:5-32). With a median follow-up in survivors of 16 months (range 5-55 months), the 18-month OS and PFS were 68% (95%CI: 47-82%) and 34% (95%CI: 15-54%), respectively. Chemorefractory disease at transplant was associated with a worse 18-month RI/POD (70% vs 18%, p=<0.01) and a markedly reduced PFS (9% vs 57%, p=0.04) and OS (53% vs 78%, p=<0.01) (Figure 1). Survival outcomes were similar between marrow-derived and peripheral blood graft source cohorts. Conclusions: HaploHCT is a feasible and effective strategy in patients with relapsed/refractory high-risk multiple myeloma. Chemorefractory disease at transplant was the only prognostic factor associated with a significant reduced RI/POD, PFS and OS. Figure Kaplan-Meier estimates of progression free survival from time of transplant of the chemosensitive and chemorefractory disease. Figure. Kaplan-Meier estimates of progression free survival from time of transplant of the chemosensitive and chemorefractory disease. Disclosures No relevant conflicts of interest to declare.

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The Safety and Therapeutic Effect Analysis of Intraoperative Intraperitoneal Chemotherapy with Lobaplatin for Hepato-Biliary-Pancreatic Cancer

10.21203/rs.3.rs-23044/v1 ◽

2020 ◽

Author(s):

Gang Chen ◽

Hao Chen ◽

Qifan Zhang ◽

Siyun Zhang ◽

Huanyu Li ◽

...

Keyword(s):

Pancreatic Cancer ◽

Intraperitoneal Chemotherapy ◽

Disease Free Survival ◽

Control Group ◽

Study Group ◽

Free Survival ◽

Significant Difference ◽

Liver And Kidney ◽

Intraperitoneal Perfusion ◽

Disease Free

Abstract Background To examine the safeness and efficacy of intraoperative intraperitoneal perfusion chemotherapy with lobaplatin on hepato-biliary-pancreatic cancer. Methods Clinical data were retrospectively collected from a total of 66 patients with HBP cancer undertaken surgeries. They were divided into two groups: the study (lobaplatin) group (33 patients) and the control group (33 patients). The disease-free survival rate, postoperative complications, and chemotherapy side effects (bone marrow, liver, and kidney toxicity) were analyzed to examine the safeness and efficacy of intraoperative intraperitoneal chemotherapy with lobaplatin. Results In the study group, two patients had a postoperative subphrenic infection and increased peritoneal effusion, one patient had postoperative leukopenia and thrombocytopenia, while the control group had postoperative abnormal coagulation function in 1 patient, and gastrointestinal bleeding in 1 patient, no significant difference in postoperative complication was observed between the two groups. There was no significant difference in the liver and kidney function between the two groups after surgery (p > 0.05). A total of 26 patients in the two groups had recurrence or metastasis within one year after surgery, including eight patients in the study group and 18 patients in the control group. The recurrence rate of hepatocellular cancer in the lobaplatin group and control was 21.14% and 60%, respectively (P = 0.012 < 0.05). But there was no significant difference in the disease-free survival function analysis (P = 0.127 > 0.05). Conclusions Intraperitoneal perfusion chemotherapy with lobaplatin is a safe and effective treatment in the process of radical resection of hepato-biliary-pancreatic tumors, which has therapeutic potential in reducing postoperative tumor recurrence and metastasis.

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Bortezomib-Based Regimens As Consolidation Therapy after Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma: A Single Center Experience from Oran (Algeria)

Blood ◽

10.1182/blood.v128.22.5121.5121 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5121-5121 ◽

Cited By ~ 1

Author(s):

Souad Talhi ◽

Soufi Osmani ◽

Mohamed Brahimi ◽

Kamila Amani ◽

Hafida Ouldjeriouat ◽

...

Keyword(s):

Stem Cells ◽

Multiple Myeloma ◽

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Progression Free Survival ◽

Consolidation Therapy ◽

Hematopoietic Stem ◽

Free Survival ◽

Significant Difference

Abstract INTRODUCTION: Autologous stem cell transplant (ASCT) is the standard of care in transplant-eligible multiple myeloma (MM) patients and is associated witha significant improvement in progression-free survival (PFS), complete remission rates (CR), and overall survival (OS). However, the majority ofpatientsrelapse. This study compares the efficacy of autologous hematopoietic stem cells followed by consolidation bybortezomibbased regimens to the no consolidation therapy in adult patients. PATIENTS AND METHODS: This is a retrospective study over a period of 7 years (2009-2015). All patients less than 65 years with a newly MM diagnosis were included. The protocol used in induction was VD (n=47) treatment whichconsisted of four 3-week cycles of 1.3 mg/m2 bortezomib administered subcutaneously (SC) on days 1, 4, 8, and 11 and 40 mg dexamethasone on days 1Ð4 and 9Ð12. Therapy with VTD was composed of four 3-week cycles of SC bortezomib and dexamethasone at the same doses and schedules as for the VD regimen plus 100 mg/day thalidomide administered orally. Therapy with VCD was composed of four 3-week cycles of SC bortezomib and dexamethasone at the same doses and schedules as for the VD regimen plus 500 mg/m2 cyclophosphamide administered orally on days 1, 8, and 15. Recommended concomitant medications included bisphosphonates, antibiotics, and antiviral prophylaxis. Acetyl salicylic acid was systematically used in the VTD arm. Stem cells were mobilized with 15 or 10 microg/kg G-CSF alone. Leukapheresis to harvest stem cells was performed on day -2 and -1. The grafts were kept in a conventional blood bank refrigerator at 4¡C until reinfusion on day 0. The target yield was 2 x106 CD34+ cells/kg. Following induction therapy, all patients had to proceed to ASCT. The conditioning regimen consisted of melphalan 200 mg/m2 in all patients.The consolidation regimen consisted of two cycles of VD or VCD or VTD after autologous stem- cell transplantation. In our study patients were divided into two groups: Group1 (ASCT plus consolidation) and Group 2 (ASCT alone). The therapeutic evaluation focused on the overall response (CR + VGPR) and progression free survival (PFS) and overall survival (OS) calculated by the Kaplan-Meier method. RESULTS: Over a period of 7 years, 153 patients were collected divided in two group: G1 (n=71) and G2 (n=82). Baseline characteristics are summarized in Table 1. No significant difference was observed between the 2 groups. In terms of CR, 58% of the patients in the G1 achieved a CR after consolidation vs 33% in the G2 after ASCT alone (p=0.007). In terms of VGPR, 31% of the patients in the G1 achieved a least a VGPR vs 17% in the G2 (p=0.04). The relapse rate was significantly lower in the G1 (10%) than the G2 (39%), (p=0.0001). The median follow-up period was 23,4 months. PFS was significantly higher in the G1, median no reached vs 37 months in the G2 (p=0.02) but no significant difference was observed in terms of OS rate between the 2 groups, 91% (G1) versus 82% (G2) at 27 months (p=0.7). CONCLUSION: We conclude thatbortezomib-based regimens as consolidation therapy after ASCT in patients with MM was effective in the improvement of PFS and response rate. Table Patients characteristics. Table. Patients characteristics. Disclosures No relevant conflicts of interest to declare.

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Interaction between KIR3DS1 and HLA-Bw4 predicts for progression-free survival after autologous stem cell transplantation in patients with multiple myeloma

Blood ◽

10.1182/blood-2010-03-273706 ◽

2010 ◽

Vol 116 (12) ◽

pp. 2033-2039 ◽

Cited By ~ 24

Author(s):

Ian H. Gabriel ◽

Ruhena Sergeant ◽

Richard Szydlo ◽

Jane F. Apperley ◽

Hugues deLavallade ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Nk Cells ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Human Leukocyte ◽

Progression Free Survival ◽

Free Survival ◽

Significant Difference

Abstract Natural killer (NK) cells exert antimyeloma cytotoxicity. The balance between inhibition and activation of NK-cells played by the inherited repertoire of killer immunoglobulin-like receptor (KIR) genes therefore may influence prognosis. One hundred eighty-two patients with multiple myeloma (MM) were analyzed for KIR repertoire. Multivariate analysis showed that progression-free survival (PFS) after autologous stem cell transplantation (ASCT) was significantly shorter for patients who are KIR3DS1+ (P = .01). This was most evident for patients in complete or partial remission (good risk; GR) at ASCT. The relative risk (RR) of progression or death for patients with KIR3DS1+ compared with KIR3DS1− was 1.9 (95% CI, 1.3-3.1; P = .002). The most significant difference in PFS was observed in patients with GR KIR3DS1+ in whom HLA-Bw4, the ligand for the corresponding inhibitory receptor KIR3DL1, was missing. Patients with KIR3DS1+KIR3DL1+HLA-Bw4− had a significantly shorter PFS than patients who were KIR3DS1−, translating to a difference in median PFS of 12 months (12.2 vs 24 months; P = .002). Our data show that KIR–human leukocyte antigen immunogenetics represent a novel prognostic tool for patients with myeloma, shown here in the context of ASCT, and that KIR3DS1 positivity may identify patients at greater risk of progression.

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Comparison of bortezomib-cyclophosphamide-dexamethasone versus bortezomib-dexamethasone based regimens in newly diagnosed multiple myeloma patients

Hematology Reports ◽

10.4081/hr.2020.8267 ◽

2020 ◽

Vol 12 (1) ◽

Author(s):

Rafiye Ciftciler ◽

Hakan Goker ◽

Yahya Buyukasik ◽

Nilgun Sayınalp ◽

Ibrahim C. Haznedaroglu ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Mortality Rate ◽

Care Center ◽

Tertiary Care ◽

Progression Free Survival ◽

Tertiary Care Center ◽

Newly Diagnosed ◽

Free Survival ◽

Significant Difference

The treatment landscape and clinical outcome of multiple myeloma (MM) patients have changed in the last decades, with an improved median survival of 8-10 years. This study aimed to evaluate the bortezomib, cyclophosphamide and dexamethasone (VCD) regimen versus bortezomib and dexamethasone (VD) regimen in patients with newly diagnosed MM. This study has been performed in a retrospective manner. One hundred and three patients with newly diagnosed MM who received chemotherapy at our tertiary care center between the years of 2009 and 2018 were evaluated. A total of 103 patients were included. The 5-year overall survival (OS) for patients who received VD regimen and patients who received VCD regimen were 75% and 83%, respectively. The OS for VD patients was 113.1±12.5 versus 122.2±9.5 months for VCD patients with no statistically significant difference (P=0.47). The 5- year PFS (progression free survival) for patients who received VD regimen and patients who received VCD regimen were 66% and 75%, respectively. The PFS for VCD patients was higher than the PFS for VD patients (67.1±7.4 versus 97.7±13.4 months), but no statistically significant difference was observed (P=0.59). Relapse rate (P=0.002) and mortality rate (P=0.01) were higher in VD group than VCD group and they were statistically significant. The OS and PFS were clinically longer in patients receiving VCD regimen than in patients receiving VD regimen, although not statistically significant. Cyclophosphamide should be given to patients at physician discretion and depending on patient’s frailty function.

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Clinical Outcomes of Non-Traditional Lenalidomide, Bortezomib, and Dexamethasone Regimens in Multiple Myeloma

Blood ◽

10.1182/blood-2020-143385 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 25-26

Author(s):

Shawn O. Streeter ◽

Omar Nadeem ◽

Paul G. Richardson ◽

Jacob P. Laubach ◽

Clifton C. Mo ◽

...

Keyword(s):

Multiple Myeloma ◽

Peripheral Neuropathy ◽

Descriptive Analysis ◽

Dose Intensity ◽

Progression Free Survival ◽

Staging System ◽

Newly Diagnosed ◽

Cutaneous Toxicity ◽

Free Survival ◽

Significant Difference

Introduction Lenalidomide, bortezomib, and dexamethasone (RVD) is a standard first-line regimen for patients with newly diagnosed multiple myeloma and is associated with high response rates and improvement in progression-free survival and overall survival compared to traditional chemotherapy regimens. Traditional (RVD Classic, RVD Lite) and non-traditional (RVD Premium Lite, RVD Ultra Lite) variations of the RVD regimen are utilized at Dana-Farber Cancer Institute (DFCI) and have not been fully evaluated in terms of safety and tolerability. RVD Premium Lite is administered in a 28-day cycle with weekly bortezomib; whereas, RVD Ultra Lite administers three weekly doses of bortezomib instead of four (Table 1). These two regimens have not been fully evaluated in terms of safety, tolerability, and efficacy. Selection is based on provider preference in addition to flexibility of dosing schedule. The regimens also allow for convenience of weekly dosing while keeping dose intensity. This retrospective, descriptive analysis is the first study to explore the safety, tolerability, and efficacy of four different RVD regimens used at DFCI. Methods This single-center, retrospective, descriptive analysis identified 90 newly diagnosed patients with multiple myeloma treated at DFCI main campus for >2 cycles of an RVD-based regimen in the front-line setting. We reviewed patients started on treatment from January 2017 to December 2019. Patients were excluded if treated primarily at an outside institution or satellite campus. Results A total of 90 patients were included between January 2017 to December 2019, and median age was 69.5 years (range 44-87). Most patients had either standard-risk or unknown cytogenetics. Of the 44 patients with available International Staging System (ISS) information, the majority were R-ISS/ISS I or II. The most common M-protein type at diagnosis was IgG (56.7%), followed by light chain restricted disease (25.6%). In terms of traditional and non-traditional RVD regimens, most patients received RVD Classic (33.3%) or RVD Ultra Lite (32.2%), followed by RVD Lite (23.3%) and RVD Premium Lite (11.1%). Patients in RVD Lite and RVD Ultra Lite groups were of older age when compared to the RVD Classic group (P<0.001). Lenalidomide dosing delays and reductions trended higher in the RVD Classic regimen at 14.3%, followed by RVD Ultra Lite at 12.3%. Bortezomib dosing delays and reductions were similar between the RVD Lite and RVD Classic regimens at 11.8% and 11.2%, respectively. Overall, combined lenalidomide and bortezomib dosing delays/reductions trended higher in the RVD Classic (14.3%/11.2%) and RVD Lite (11.0%/11.8%) compared to RVD Ultra Lite (12.3%/9%) and RVD Premium Lite (10.8%/9.6%). The most common toxicities noted with all variations of the RVD regimen were peripheral neuropathy, cutaneous toxicity, infection, diarrhea, and constipation. The highest rates of adverse events among all RVD regimens were infection and peripheral neuropathy. Peripheral neuropathy was slightly higher in the RVD Premium Lite and RVD Classic regimen at 8.43% and 8.70%, respectively, compared to RVD Lite and RVD Ultra Lite at 7.1% and 7.7%, respectively. No significant difference in toxicities were seen when regimens were compared (p=0.1369). Intolerance leading to therapy change trended higher in the RVD Lite group at 23.8%, followed by RVD Classic and RVD Ultra Lite at 16.7% and 10.3%, respectively. Nineteen percent of patients in the RVD Lite group had minimal response or progression leading to therapy change, which was highest among all RVD regimens. Rate of transplant was highest in the RVD Classic group at 36.7%, followed by RVD Premium Lite at 20%. There was no significant difference in intolerance, minimal response or progression, maintenance, continued induction or planned change, transplant, and death between regimens (p=0.089). In terms of progression-free survival, no differences were seen between the groups (p=0.36). Conclusion In conclusion, the current investigation allowed us to assess the safety, tolerability, and efficacy of traditional and non-traditional variations of the RVD regimen in multiple myeloma used at our institution. There are minimal differences between each regimen when toxicities are managed appropriately. Disclosures Richardson: Celgene/BMS, Oncopeptides, Takeda, Karyopharm: Research Funding. Mo:Celgene/BMS: Membership on an entity's Board of Directors or advisory committees.

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T Regulatory CD4+CD25+FoxP3+ Lymphocytes in the Peripheral Blood of Left-Sided Colorectal Cancer Patients

Medicina ◽

10.3390/medicina55060307 ◽

2019 ◽

Vol 55 (6) ◽

pp. 307 ◽

Cited By ~ 2

Author(s):

Katarzyna Dylag-Trojanowska ◽

Joanna Rogala ◽

Radoslaw Pach ◽

Maciej Siedlar ◽

Jaroslaw Baran ◽

...

Keyword(s):

Colorectal Cancer ◽

Peripheral Blood ◽

Absolute Number ◽

Tumor Location ◽

Control Group ◽

Study Group ◽

Host Immune System ◽

Term Survival ◽

Entire Study ◽

Significant Difference

Background and objectives: T regulatory lymphocytes (Treg) are one of the subsets of T-lymphocytes involved in the interaction of neoplastic tumors and the host immune system, and they may impair the immune reaction against cancer. It has been shown that Treg are increased in the peripheral blood of patients with various cancers. In colorectal cancer, the prognostic role of Treg remains controversial. Colorectal cancer is a heterogenous disease, with many variations stemming from its primary tumor location. The aim of this study is to analyse the relationship between the amount of Treg in the peripheral blood of patients with left-sided colorectal cancer in various stages of disease and long-term survival. Materials and Methods: A prospective analysis of 94 patients with left-sided colorectal cancer and a group of 21 healthy volunteers was carried out. Treg levels in peripheral blood were analysed using flow cytometry. Results: There was a statistically significant difference between the amount of Treg in the Ist and IInd TNM stages (p = 0.047). The number of Treg in the entire study group was significantly lower than in the control group (p = 0.008) and between patients in stages II and III and the control group (p = 0.003 and p = 0.018). The group of pT3+pT4 patients also had significantly lower Treg counts in their peripheral blood than the control group (p = 0.005). In the entire study group, the level of Treg cells in the peripheral blood had no influence on survival. The analysis of the TNM stage subgroups also showed no difference in survival between patients with “low” and “high” Treg counts. Conclusion: The absolute number of Treg in the peripheral blood of patients with left-sided colorectal cancer was significantly decreased in comparison to healthy controls, especially for patients with stage II+III disease. Treg presence in the peripheral blood had no impact on survival.

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