Allogeneic Transplantation in Multiple Myeloma: Long-Term Follow-Up and Cytogenetic Subgroup Analysis

2019 ◽  
Author(s):  
Stefan Knop ◽  
Monika Engelhardt ◽  
Peter Liebisch ◽  
Christoph Meisner ◽  
Ernst Holler ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Subgroup Analysis ◽  
Allogeneic Transplantation ◽  
Long Term Follow Up

Allogeneic transplantation in multiple myeloma: long-term follow-up and cytogenetic subgroup analysis

Leukemia ◽  
2019 ◽  
Vol 33 (11) ◽  
pp. 2710-2719 ◽  
Author(s):  
Stefan Knop ◽  
◽  
Monika Engelhardt ◽  
Peter Liebisch ◽  
Christoph Meisner ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Subgroup Analysis ◽  
Allogeneic Transplantation ◽  
Long Term Follow Up

scholarly journals Allogeneic Transplantation in Multiple Myeloma—Does It Still Have a Place?

2020 ◽  
Vol 9 (7) ◽  
pp. 2180
Author(s):  
Gösta Gahrton ◽  
Simona Iacobelli ◽  
Laurent Garderet ◽  
Ibrahim Yakoub-Agha ◽  
Stefan Schönland
Keyword(s):  
Multiple Myeloma ◽  
Proteasome Inhibitors ◽  
Allogeneic Transplantation ◽  
Reduced Intensity Conditioning ◽  
Cell Therapies ◽  
Novel Drugs ◽  
Car T ◽  
Long Term Follow Up

Novel drugs have improved survival for patients with multiple myeloma in recent years. However, the disease is still fatal. Allogeneic stem cell transplantation (Allo) has proven to cure some patients with the disease, but its role is controversial due to relatively high transplant-related toxicity and mortality (nonrelapse mortality, NRM). Using nonmyeloablative reduced-intensity conditioning (RIC), both toxicity and NRM can be reduced, and RICAllo is, therefore, an option for subgroups of patients. Upfront tandem autologous/RICAllo (Auto/RICAllo) was shown to be superior to single Auto or tandem Auto/Auto in both progression-free (PFS) and overall survival (OS) in two prospective studies with long-term follow-up, while three similarly designed studies did not detect a difference. A recent update of pooled patient data from four of these studies showed significantly superior PFS and OS with Auto/RICAllo. Importantly, none of these studies showed inferior results with Auto/RICAllo in patients less than 70 years of age. Auto/RICAllo appears to overcome some poor risk cytogenetic markers. Encouraging results have also been seen in treatment of relapsed patients. Combining Allo with new proteasome inhibitors and immunomodulatory drugs may further improve results. Other encouraging new cell therapies such as with CAR T-cells, NK- and CAR NK-cells may well have a place in combination with RICAllo. Such studies are warranted.

scholarly journals Late relapses following reduced intensity allogeneic transplantation in patients with multiple myeloma: a long-term follow-up study

2012 ◽  
Vol 160 (2) ◽  
pp. 199-206 ◽  
Author(s):  
Firoozeh Sahebi ◽  
Yan Shen ◽  
Sandra H. Thomas ◽  
Amalia Rincon ◽  
Joyce Murata-Collins ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Allogeneic Transplantation ◽  
Follow Up Study ◽  
Long Term Follow Up ◽  
Reduced Intensity

Outcome of allogeneic transplantation in newly diagnosed and relapsed/refractory multiple myeloma: long-term follow-up in a single institution

2016 ◽  
Vol 97 (5) ◽  
pp. 479-488 ◽  
Author(s):  
Laurens E. Franssen ◽  
Reinier A. P. Raymakers ◽  
Arjan Buijs ◽  
Marian F. Schmitz ◽  
Suzanne van Dorp ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Allogeneic Transplantation ◽  
Newly Diagnosed ◽  
Single Institution ◽  
Refractory Multiple Myeloma ◽  
Long Term Follow Up

scholarly journals Bortezomib, doxorubicin and dexamethasone (PAD) front-line treatment of multiple myeloma: updated results after long-term follow-up

2008 ◽  
Vol 141 (4) ◽  
pp. 512-516 ◽  
Author(s):  
Rakesh Popat ◽  
Heather E. Oakervee ◽  
Simon Hallam ◽  
Nicola Curry ◽  
Liz Odeh ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Line Treatment ◽  
Front Line ◽  
Long Term Follow Up

scholarly journals The Necessary for Long-Term Follow-up of Mutated Genes and Clonal Evolutions in Multiple Myeloma Combined with cfDNA Assay

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5515-5515
Author(s):  
Yuko Mishima ◽  
Yuji Mishima ◽  
Masahiro Yokoyama ◽  
Noriko Nishimura ◽  
Yoshiharu Kusano ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Genomic Dna ◽  
Research Funding ◽  
Somatic Mutations ◽  
Clinical Course ◽  
Bone Marrow Aspiration ◽  
Long Term Follow Up

Introduction)Somatic mutations in multiple myeloma (MM) are strongly related to the clinical outcome and clonal evolution over the clinical course, and are a major problem. From a clinical viewpoint, although numerous novel drugs have been utilized, achieving long-lasting and complete remission remains difficult. Recent studies have elucidated the mutated genes using next-generation sequencing, and have examined how clonal change can be acquired in myeloma. In this study, we traced the transition of the somatic mutations of bone marrow tumor cells in patients with MM over a long-term follow-up. Furthermore, we compared the somatic mutations found in serum cell-free DNA (cfDNA) and mutated genes obtained from bone marrow myeloma cells. Material and Methods)Patients diagnosed with multiple myeloma who provided written informed consent to participate in the study were enrolled. Patients were treated by immuno-chemotherapy with or without radiation between 2000 and 2017 at our institute. Bone marrow aspiration and biopsy were performed at the time of diagnosis and upon disease progression. Around the time of bone marrow aspiration, serum was obtained from a peripheral blood sample for cfDNA analysis. Myeloma cells were separated from bone marrow samples with MicroBeads of CD138 antibody and genomic DNA was extracted. The peripheral blood samples derived from myeloma patients. The cfDNA was extracted from the serum using a Maxwell RSC cfDNA Plasma kit. Using genomic DNA derived from cfDNA and bone marrow, multiplex polymerase chain reaction (PCR) was performed, and a sequence library was then constructed with an Ion Custom Amplicon panel. The panel for the sequence library was designed using an Ion AmpliSeq DesignerTM. 126 targeted genes were selected. The genomes were sequenced using the Ion ProtonTM System. This protocol was approved by the institutional review board and the Genomic Review Board of the Japanese Foundation for Cancer Research. Result)We followed 7 patients' long term-clinical course and the transition of mutations (8.5 year average). The expression of myeloma driver genes, such as RAS, BRAF, and MYC, were not critical. We did, however, detect a relationship between an increase in the dominant mutated gene, such as TP53, DIS3, FAM46C, KDM6B, and EGR1 and poor prognosis in patients with myeloma. Next, we calculated the cfDNA concentrations from 34 cases. The cfDNA concentrations were significantly higher than 10 control cases (average 62.0 ng/mL (0-200 ng/mL) and 8.18 ng/mL (4.3-14.1 ng/mL), P=0.0046). The 2.5 year-progression free survival (PFS) during the first treatment of MM were tend to be poorer in the group with cfDNA>50 ng/mL (72.9%) than the group with cfDNA<50 ng/mL(25.9%), however there are no statistical significance (P = 0.15).We caluculated concordance rate of derived mutations from bone marrow MM cells and cfDNA in 7 cases. The somatic mutations found in serum cell-free DNA (cfDNA) and bone marrow MM cells were determined the correlation coefficients. However, there are few difference expression pattern in each source. In cfDNA assay, CREEP, EGR1, HDAC4, HDAC6, and JMJD1C were highly expressed as 57.1% (4/7) - 85.7% (6/7), and these results were almost the same as those for bone marrow MM cells. On the other hand, KDM1A (85.7%), PI3KCD (71.4%), and KDM3B (57.1%) were highly detected in cfDNA, although those were not frequently expressed in bone marrow. Discussion)Our data demonstrate the importance of the long-term follow-up of somatic mutations during the clinical course of myeloma. Serum cfDNA is a useful alternative source for detecting somatic mutations in MM patients during long-term follow-up. Disclosures Mishima: Chugai-Roche Pharmaceuticals Co.,Ltd.: Consultancy. Yokoyama:Chugai-Roche Pharmaceuticals Co.,Ltd.: Consultancy. Nishimura:Chugai-Roche Pharmaceuticals Co.,Ltd.: Consultancy; Celgene K.K.: Honoraria. Hatake:Celgene K.K.: Research Funding; Janssen Pharmaceutical K.K.: Research Funding; Takeda Pharmaceutical Co.,Ltd.: Honoraria. Terui:Bristol-Myers Squibb K.K.: Research Funding; Bristol-Myers Squibb, Celgene, Janssen, Takeda, MSD, Eisai, Ono, and Chugai-Roche Pharmaceuticals Co.,Ltd.: Honoraria.

scholarly journals Localized and indolent myeloma

Blood ◽  
1980 ◽  
Vol 56 (3) ◽  
pp. 521-525 ◽  
Author(s):  
R Alexanian
Keyword(s):  
Multiple Myeloma ◽  
Bone Lesions ◽  
Term Outcome ◽  
Myeloma Protein ◽  
Long Term Outcome ◽  
Long Term Follow Up ◽  
Tumor Load ◽  
Localized Disease

Abstract Criteria were defined for recognizing 29 patients with a localized plasmacytoma of bone and 20 patients with an indolent variety of multiple myeloma in order to justify long-term follow-up without chemotherapy. All patients with indolent myeloma were asymptomatic from their low tumor mass disease, had a hemoglobin greater than 10 g/dl, and showed no more than 3 lytic bone lesions. The presence of more than 200 mg/day of Bence Jones protein was usually followed by disease progression within 2 yr. Serial assessments of myeloma protein level provided a useful index of changing tumor load and the need for chemotherapy. In patients with localized disease, radiotherapy usually reduced myeloma proteins markedly with subsequent disease control for many years, even though small serum peaks persisted. Chemotherapy for multiple myeloma was not required for a median of 8 yr in patients presenting with localized disease and of 3 yr in those with indolent myeloma. The additional survival from the start of drug treatment was similar to that of comparable patients treated promptly for overt multiple myeloma. The delay of chemotherapy until evidence of tumor progression did not affect the long-term outcome of patients with localized or indolent myeloma.

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