I just took a quick look at the ASCO 2016 abstracts that were posted over here:
"ASCO 2016 multiple myeloma-related poster presentations" (page at The Beacon)
When I saw this one,
Neppalli, A.K., et al, "Long-term outcomes of high-dose melphalan and carmustine followed by autologous hematopoietic cell transplantation for multiple myeloma," ASCO 2016 abstract 8026 (link to abstract)
I thought I would post it in this thread.
I started this thread off by looking at ASH 2015 abstracts to see if it looked like any myeloma patients were currently being cured. This study only mentions adding high dose BCNU to high dose melphalan for autos. No mention of induction or maintenance used. As I mentioned earlier in the thread, studies that discuss plateaus on progression free survival curves in the non-allo setting typically start to show a flattening at 10 years or more. This study mentions a much earlier potential plateau (3 years) for the group transplanted in CR.
While it may be too early to start thinking these patients are cured (at least in my opinion), I wanted to post it here for two reasons.
The first is I have made references in the past that it is surprising that no improved conditioning for autos has come along for so many years and the group at Stanford used this conditioning for 414 patients. Kudos to them for attempting to improve the efficiency of the procedure.
The other is that I see many newly diagnosed patients ask why a patient would opt for a transplant if they are already in CR after induction. Here is one reason:
"However, relapse in patients entering AHCT in CR reached a plateau at approximately 3 years post-transplant, while patients with measurable disease at AHCT relapsed continuously over time."
"High-dose conditioning with BCNU/melphalan followed by AHCT was safe and effective in this large cohort of patients with myeloma, with outcomes comparable or superior to those reported in registry data (Costa et al., BBMT 2014). Patients benefited regardless of disease status at AHCT; a subset of patients transplanted in CR may achieve long-term cure, based on the plateau in relapse incidence in this group. Pneumonitis remains a concern with BCNU-containing regimens. Further studies directly comparing this regimen to single-agent melphalan are needed."
I will definitely be interested to see more detail on this study in the future. Only 68 patients did the auto in CR and no mention of the relapse rate up to year 3. Hopefully as time goes on the plateau will hold and we will see that some patients were cured. The BCNU does appear to add some toxicity.
"Pneumonitis related to BCNU occurred in 104 of 414 patients (25%) and caused 2 deaths. Second malignancies (excluding non-melanomatous skin cancers) occurred in 29 patients (7%) at a median of 16 months post-transplant."
Forums
Re: Progress toward a multiple myeloma cure?
I hadn’t realized that until just recently no reliable animal models existed of multiple myeloma, but below is an interesting article on the recent development of an animal model of multiple myeloma which should help researchers better understand the mechanisms of the disease and work towards developing a cure.
"Sylvester Researchers Develop Novel Disease Model to Study Multiple Myeloma," Press Release - University of Miami, May 17, 2016 (link to press release)
Excerpt:
Researchers at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine have developed an animal model that allows them to better understand the mechanisms that lead to the development of multiple myeloma, a hematologic cancer of plasma cells, and the amyloidosis that sometimes accompanies it. The study was published in the journal Scientific Reports ...
The new animal model of multiple myeloma was generated when a team of researchers from Sylvester and Memorial Sloan Kettering Cancer Center in New York crossed two genetically modified mice — mice lacking the Mef gene and mice with a Rad50 gene mutation (Rad50s). Mef, also called Elf4, is a transcription factor — originally cloned in the Nimer lab — that is known to both promote and suppress the formation of cancers. Rad50 is a component of a sensor of DNA damage induced by various stresses, and it regulates the DNA damage-response pathways in cells.
Related journal article:
Asai, T, et al,, "Generation of a novel, multi-stage, progressive, and transplantable model of plasma cell neoplasms," Scientific Reports, March 10, 2016 (full text of article)
Abstract
Multiple myeloma is a plasma cell neoplasm with an extremely variable clinical course. Animal models are needed to better understand its pathophysiology and for preclinical testing of potential therapeutic agents. Hematopoietic cells expressing the hypermorphic Rad50s allele show hematopoietic failure, which can be mitigated by the lack of a transcription factor, Mef/Elf4. However, we find that 70% of Mef−/−Rad50s/s mice die from multiple myeloma or other plasma cell neoplasms. These mice initially show an abnormal plasma cell proliferation and monoclonal protein production, and then develop anemia and a decreased bone mineral density. Tumor cells can be serially transplanted and according to array CGH and whole exome sequencing, the pathogenesis of plasma cell neoplasms in these mice is not linked to activation of a specific oncogene, or inactivation of a specific tumor suppressor. This model recapitulates the systemic manifestations of human plasma cell neoplasms, and implicates cooperativity between the Rad50s and Mef/Elf4 pathways in initiating myelomagenic mutations that promote plasma cell transformation.
"Sylvester Researchers Develop Novel Disease Model to Study Multiple Myeloma," Press Release - University of Miami, May 17, 2016 (link to press release)
Excerpt:
Researchers at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine have developed an animal model that allows them to better understand the mechanisms that lead to the development of multiple myeloma, a hematologic cancer of plasma cells, and the amyloidosis that sometimes accompanies it. The study was published in the journal Scientific Reports ...
The new animal model of multiple myeloma was generated when a team of researchers from Sylvester and Memorial Sloan Kettering Cancer Center in New York crossed two genetically modified mice — mice lacking the Mef gene and mice with a Rad50 gene mutation (Rad50s). Mef, also called Elf4, is a transcription factor — originally cloned in the Nimer lab — that is known to both promote and suppress the formation of cancers. Rad50 is a component of a sensor of DNA damage induced by various stresses, and it regulates the DNA damage-response pathways in cells.
Related journal article:
Asai, T, et al,, "Generation of a novel, multi-stage, progressive, and transplantable model of plasma cell neoplasms," Scientific Reports, March 10, 2016 (full text of article)
Abstract
Multiple myeloma is a plasma cell neoplasm with an extremely variable clinical course. Animal models are needed to better understand its pathophysiology and for preclinical testing of potential therapeutic agents. Hematopoietic cells expressing the hypermorphic Rad50s allele show hematopoietic failure, which can be mitigated by the lack of a transcription factor, Mef/Elf4. However, we find that 70% of Mef−/−Rad50s/s mice die from multiple myeloma or other plasma cell neoplasms. These mice initially show an abnormal plasma cell proliferation and monoclonal protein production, and then develop anemia and a decreased bone mineral density. Tumor cells can be serially transplanted and according to array CGH and whole exome sequencing, the pathogenesis of plasma cell neoplasms in these mice is not linked to activation of a specific oncogene, or inactivation of a specific tumor suppressor. This model recapitulates the systemic manifestations of human plasma cell neoplasms, and implicates cooperativity between the Rad50s and Mef/Elf4 pathways in initiating myelomagenic mutations that promote plasma cell transformation.
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KarenaD - Name: Karen
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: November 4, 2015
- Age at diagnosis: 54
Re: Progress toward a multiple myeloma cure?
Greetings,
In my last appointment, I was told by my doctor ( a respected myeloma specialist) that he believes a cure is possible within the next 5 years! I was taken aback. You see, my doctor is not your "feel good" doctor, but a no-nonsense scientist. So I am very encouraged. He believes that the breakthrough will probably come from the CAR T-cell efforts.
Kind Regards & Happy Holidays,
Frank
In my last appointment, I was told by my doctor ( a respected myeloma specialist) that he believes a cure is possible within the next 5 years! I was taken aback. You see, my doctor is not your "feel good" doctor, but a no-nonsense scientist. So I am very encouraged. He believes that the breakthrough will probably come from the CAR T-cell efforts.
Kind Regards & Happy Holidays,
Frank
Re: Progress toward a multiple myeloma cure?
That would be wonderful. While I'm hesitant to believe it until I see it, I suspect that the next 5 years will bring around increased overall survival rates for sure.
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countrygirl - Name: Countrygirl
- Who do you know with myeloma?: IgG MGUS
- When were you/they diagnosed?: September 2016
- Age at diagnosis: 35
Re: Progress toward a multiple myeloma cure?
Lets also not forget about the promise of nanotechnology and its potential to treat or cure multiple myeloma and other cancers. These will be more than 5 years out, most likely, but there is hope for a cure.
Some quick links:
NCI Alliance for Nanotechnology in Cancer - Center for Multiple Myeloma Nanotherapy:
https://nano.cancer.gov/action/programs/washup3/index.asp
Nanotherapy effective in mice with multiple myeloma:
https://source.wustl.edu/2015/05/nanotherapy-effective-in-mice-with-multiple-myeloma/
http://mct.aacrjournals.org/content/14/6/1286
Some quick links:
NCI Alliance for Nanotechnology in Cancer - Center for Multiple Myeloma Nanotherapy:
https://nano.cancer.gov/action/programs/washup3/index.asp
Nanotherapy effective in mice with multiple myeloma:
https://source.wustl.edu/2015/05/nanotherapy-effective-in-mice-with-multiple-myeloma/
http://mct.aacrjournals.org/content/14/6/1286
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PositiveChris - Name: Chris
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: 11/28/2016
- Age at diagnosis: 42