It is clear that there are no universally agreed protocols for the treatment of multiple myeloma, with differing of opinions, choices of treatment regimens / dosages by treating clinicians, not related to either cytogenetics or GEP. Risk stratification for treatment as proposed by Mayo is not universally applied, although it makes sense. Even evidence from research is not universally applied by treating clinicians from my experience because they are one step behind.
So length of survival remains rather a case of luck depending on many factors, including individualistic ones. The top institutions with the most prolific research and experience tend to do better in terms of median survival figures, individual factors such as comorbidities aside.
The survival data tend to include those who have and have not had autologous stem cell transplant (ASCT) or allogeneic transplants (allos), but is there any data that separates out survival range for 'younger cohorts' not having ASCT or allo, but treated either continuously or discontinuously with novel drug regimens?
Any information would be welcome.
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Re: Survival figures for multiple myeloma without ASCT
Dear Edna,
You are absolutely right in stating that the overall survival of a patient with myeloma depends on many factors. It is indeed a heterogeneous disease with markedly disparate outcomes that depend on a number of disease (myeloma) and host (patient) related prognostic factors.
We at Mayo Clinic have looked at different approaches in treating young patients. While the study I am quoting here (U Painuly et al, "Survival Outcomes Of Very Young (<40 years) Myeloma Patients," ASH 2013 Annual Meeting abstract #2136)) does not directly answer your question about the outcome of patients who have received novel agents alone, it states that integration of auto transplant (ASCT) to the novel agent-based approach has benefited the patients the most.
The results of the DETERMINATION trial (IFM/DFCI 2009 study), which randomizes patients to ASCT + novel agents vs. novel agents alone, would shed some more light on the two approaches, but are not expected to be announced before December 2015. Results indicating very good outcomes were recently published in a Phase 2 French study (see JCO 2014 reference below) that utilized the same approach as is being utilized in the transplant arm of IFM/DFCI 2009 study.
A Phase III Italian study recently attempted to answer this important question as well, and the arm that received an integrated approach of novel agents, ASCT + Revlimid maintenance fared the best. However, the control arm in that study received a suboptimal therapy of an abbreviated course of Revlimid + dex followed by melphalan, prednisone +Revlimid, an approach that cannot be totally considered novel agent-based (see NEJM 2014 reference below).
Despite the limited data, when dealing with young patients, I tend to recommend an integrated approach that utilizes upfront novel agent-based induction, followed by a single auto stem cell transplant , consolidation, and maintenance (depending of risk profile) therapy. Postponing ASCT may not be the most suitable approach, as a proportion of patients may become ineligible for ASCT at the time of relapse due to development of new medical issues, a problem that was highlighted in the Italian study.
Prashant
References:
M Roussel et al., “Front-Line Transplantation Program With Lenalidomide, Bortezomib, and Dexamethasone Combination As Induction and Consolidation Followed by Lenalidomide Maintenance in Patients With Multiple Myeloma: A Phase II Study by the Intergroupe Francophone du Myélome,” Journal of Clinical Oncology, July 14, 2014 (link to abstract)
A Palumbo et al., "Autologous Transplantation and Maintenance Therapy in Multiple Myeloma," The New England Journal of Medicine, September 4, 2014 (link to full text of article)
Related Beacon news articles and forum discussions:
Article about the Roussel JCO study: "Treatment Regimen Featuring Revlimid-Velcade-Dexamethasone Therapy And Stem Cell Transplantation Yields Deep Responses In Newly Diagnosed Multiple Myeloma," The Myeloma Beacon, July 16, 2014
Forum discussion about the Palumbo NEJM study: "NEJM article on transplantation & Revlimid maintenance," started Sep 4, 2014.
You are absolutely right in stating that the overall survival of a patient with myeloma depends on many factors. It is indeed a heterogeneous disease with markedly disparate outcomes that depend on a number of disease (myeloma) and host (patient) related prognostic factors.
We at Mayo Clinic have looked at different approaches in treating young patients. While the study I am quoting here (U Painuly et al, "Survival Outcomes Of Very Young (<40 years) Myeloma Patients," ASH 2013 Annual Meeting abstract #2136)) does not directly answer your question about the outcome of patients who have received novel agents alone, it states that integration of auto transplant (ASCT) to the novel agent-based approach has benefited the patients the most.
The results of the DETERMINATION trial (IFM/DFCI 2009 study), which randomizes patients to ASCT + novel agents vs. novel agents alone, would shed some more light on the two approaches, but are not expected to be announced before December 2015. Results indicating very good outcomes were recently published in a Phase 2 French study (see JCO 2014 reference below) that utilized the same approach as is being utilized in the transplant arm of IFM/DFCI 2009 study.
A Phase III Italian study recently attempted to answer this important question as well, and the arm that received an integrated approach of novel agents, ASCT + Revlimid maintenance fared the best. However, the control arm in that study received a suboptimal therapy of an abbreviated course of Revlimid + dex followed by melphalan, prednisone +Revlimid, an approach that cannot be totally considered novel agent-based (see NEJM 2014 reference below).
Despite the limited data, when dealing with young patients, I tend to recommend an integrated approach that utilizes upfront novel agent-based induction, followed by a single auto stem cell transplant , consolidation, and maintenance (depending of risk profile) therapy. Postponing ASCT may not be the most suitable approach, as a proportion of patients may become ineligible for ASCT at the time of relapse due to development of new medical issues, a problem that was highlighted in the Italian study.
Prashant
References:
M Roussel et al., “Front-Line Transplantation Program With Lenalidomide, Bortezomib, and Dexamethasone Combination As Induction and Consolidation Followed by Lenalidomide Maintenance in Patients With Multiple Myeloma: A Phase II Study by the Intergroupe Francophone du Myélome,” Journal of Clinical Oncology, July 14, 2014 (link to abstract)
A Palumbo et al., "Autologous Transplantation and Maintenance Therapy in Multiple Myeloma," The New England Journal of Medicine, September 4, 2014 (link to full text of article)
Related Beacon news articles and forum discussions:
Article about the Roussel JCO study: "Treatment Regimen Featuring Revlimid-Velcade-Dexamethasone Therapy And Stem Cell Transplantation Yields Deep Responses In Newly Diagnosed Multiple Myeloma," The Myeloma Beacon, July 16, 2014
Forum discussion about the Palumbo NEJM study: "NEJM article on transplantation & Revlimid maintenance," started Sep 4, 2014.
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Dr. Prashant Kapoor - Name: Prashant Kapoor, M.D.
Beacon Medical Advisor
Re: Survival figures for multiple myeloma without ASCT
Many thanks for your response Dr Kapoor. I am impressed with the Mayo Clinic's risk stratification approach to treatment, yet to be universally adopted. I look forward to the results of the DETERMINATION trial.
As you point out, the drug regimens used to do not always correspond to what is understood by the term novel agents in the treatment of multiple myeloma.
There are so many factors at play in outcomes and the presentation of results as pooled median or averages does not really give an idea of what pre-existing and ongoing health status leads to longer survival. The importance of skilled supporting treatment instituted in a timely manner when needed is an issue little mentioned as affecting outcomes / survival.
I suppose what I want to have is some idea of is the OS curve for those of transplant eligible age who are treated with novel drugs who might not have HDT / ASCT because of greater risks of problems occurring.
As you point out, the drug regimens used to do not always correspond to what is understood by the term novel agents in the treatment of multiple myeloma.
There are so many factors at play in outcomes and the presentation of results as pooled median or averages does not really give an idea of what pre-existing and ongoing health status leads to longer survival. The importance of skilled supporting treatment instituted in a timely manner when needed is an issue little mentioned as affecting outcomes / survival.
I suppose what I want to have is some idea of is the OS curve for those of transplant eligible age who are treated with novel drugs who might not have HDT / ASCT because of greater risks of problems occurring.
3 posts
• Page 1 of 1