Download Issue III: Focus on Multiple Myeloma

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WHAT’S INSIDE:
• ASBMT guidelines for multiple myeloma
• Review: How to treat high-risk myeloma
• Improved survival in multiple myeloma
over time
Visit us at:
kucancercenter.org/BMT or kumed.com/BMT
Volume III, Issue 3;
Focus on: Multiple Myeloma
An update on HCT research and clinical trends in multiple
myeloma to help guide treatment choices.
Transplant Connection is developed by the National Marrow Donor Program/Be The Match in support of its Network partnership with The University of Kansas Hospital.
Volume III, Issue 3;
Focus on: Multiple Myeloma
HCT Research on Multiple Myeloma
Welcome to Transplant Connection, The University of Kansas Cancer Center (KUCC)
newsletter focusing on trends in the treatment of hematologic malignancies. This edition
focuses on perspectives on multiple myeloma with new ASBMT recommendations,
treatment strategies for high-risk patients and survival trends. Stay up-to-date by viewing
additional short summaries of the latest research in multiple myeloma and other
hematologic malignancies. Visit BeTheMatchClinical.org/Research.
HCT for Multiple Myeloma:
Updated Guidelines from the ASBMT
— Siddhartha Ganguly, MD, FACP; University of Kansas Medical Center
Therapeutic strategies for multiple myeloma (MM) have changed dramatically over the last
decade. The American Society for Blood and Marrow Transplantation (ASBMT) recently
updated its guidelines for using hematopoietic cell transplantation (HCT) in the treatment
of MM based on an extensive review of recent literature. [1] In this evidence-based
review, the ASBMT guidelines committee makes recommendations on several aspects of
transplantation for MM, including patient selection, timing of transplantation, autologous
vs. allogeneic HCT, and post-transplant follow-up strategies.
Dear Colleague,
We value this opportunity to share the
latest in HCT research and news with you
and hope you find it useful. In 2016, the
format of our newsletter will change from
print to an electronic newsletter. I invite
you to sign up at kucancercenter.org/
signup to receive it in your inbox.
As the year comes to a close, I would like
to thank you for your partnership with us
to care for your
patients with
hematologic
malignancies.
Our team looks
forward to new
collaborations
with you in 2016.
Joseph P. McGuirk, DO
Director, Blood and Marrow Transplant (BMT) Program
The University of Kansas Cancer Center
BMT program highlights
Timing of transplant: Early vs. late
A significant survival advantage of autologous HCT over conventional chemotherapy has
been shown in many earlier studies. However, controversy exists regarding proper timing of
referring patients with MM to a transplant center. There is no published prospective
randomized study answering this question, and in the era of novel agents, previous clinical
practices may need to be revisited.
Earlier prospective data by French groups showed an autologous HCT benefit in event-free
survival and time without symptoms. [2] And retrospective studies show that delayed
transplant is feasible in the modern era, but these results are not a substitute for
prospective randomized data.
The multi-center DFCI 10-106 (NCT01208662) trial is structured to answer the exact
same question in the era of novel combination therapy. Until the reports are available, the
ASBMT guidelines recommend continuing with the practice of early (up-front) autologous
HCT in MM.
What about those patients who are refractory or failed to attain at least a PR from the
initial induction therapy?
Status at the time of transplantation correlates well with the remission status after
transplantation. Patients who are refractory or fail to attain at least a partial remission
(PR) after an initial combination therapy pose a challenge to treating physicians. Results of
earlier retrospective studies demonstrated that additional therapy or changing therapy did
not seem to change survival. Although prospective data are lacking, the ASBMT guidelines
committee recommends consideration of first autologous HCT in refractory disease.
HCT for Multiple Myeloma: continued on page 2
• Region’s largest BMT and acute leukemia
program, including photopheresis and
clinical trials.
• Region’s first BMT program accredited by
the Foundation for Accreditation of Cellular
Therapy, or FACT. Received fifth
accreditation in 2014.
• More than 3,000 successful transplants.
• Designated as a BMT-CTN core center.
• Designated as a Center of Excellence for all
payers that utilize this distinction.
• Network member of the National Marrow
Donor Program since 1995.
• Medicare-approved since 1977.
Review: How to Treat High-Risk Myeloma
In this installment of the “How I treat ...” series in Blood, the authors
take a case-based approach to review the treatment of patients with
genetically or clinically defined high-risk myeloma, and discuss their
clinical decision-making process when selecting among treatment
options for these patients. [1]
The authors note that the best long-term outcomes are achieved if
physicians identify high-risk myeloma patients at the time of disease
presentation, so that patients can receive aggressive combination
therapy followed by long-term maintenance therapy. The authors
outline risk-stratification using disease stage, chromosomal
abnormalities, disease biology, and gene expression.
Conventional chemotherapy in various combinations is insufficient
to overcome or even mitigate the impact of high-risk myeloma,
according to the authors. Their suggested treatment algorithm
begins with high-dose therapy with early autologous transplantation
and continues with risk-adapted maintenance therapy.
Aggressive induction therapies discussed in this review include RVD
(lenalidomide, bortezomib, and dexamethasone), VTD (bortezomib,
thalidomide, and dexamethasone), CTD (cyclophosphamide,
thalidomide, and dexamethasone), and CRD (carfilzomib,
lenalidomide, and dexamethasone), as used in the large cooperative
group trials in Europe and the United States. Such therapies avoid
the use of alkylating agents and are designed to prevent the
emergence of drug resistance, with the ultimate goal of suppressing
clonal evolution.
A key aspect of treating this aggressive disease is an aggressive
monitoring schedule, according to the authors, who note that “any
opportunity the tumor is given to grow and develop drug resistance
represents a potential source for tumor escape.” They therefore
recommend minimizing the period with no therapy to 60 days
rather than the conventional 100 days for the initiation of
maintenance therapy.
Finally, the role of transplantation in these patients is reviewed
with recommendations for which patients with high-risk myeloma
would benefit most from high-dose therapy and autologous
transplantation, planned tandem autologous transplantation,
or allogeneic transplantation within a clinical trial. The NMDP/Be The
Match and ASBMT guidelines on the timing for transplant
consultation are listed in Table 1.
Transplant consultation guidelines for Multiple Myeloma
All patients after initiation of therapy
At first progression
Table 1. View complete guidelines at BeTheMatchClinical.org/guidelines
1.
Lonial S, Boise LH, Kaufman J. How I treat high-risk myeloma. Blood: 2015;
126(13): 1536-1543.
HCT for Multiple Myeloma: continued from page 1
Role of second transplantation as a salvage therapy for
relapsed MM
Unfortunately, the majority of patients after first autologous HCT will
eventually relapse. Although there are several available options for
patients with relapsed disease, a second autologous HCT should be
considered for select patients, especially for those who relapse later
than 12 months after the first autologous transplant. National
Comprehensive Cancer Network (NCCN) guidelines recommend
collecting for at least two autologous grafts for eligible patients in
the event a second transplant is needed for salvage after relapse.
Progression-free survival is an acceptable outcome in a relapsed
setting. Based on this observation, and review of retrospective data,
the ASBMT guidelines committee states that second autologous
transplant is safe and efficacious for patients with relapsed MM and
should be considered in a salvage setting.
Who needs maintenance after transplantation?
In the era of novel agents, maintenance and consolidation are
attractive options after autologous transplantation for MM. Two
large prospective randomized trials (IFM/French and CALGB/USA)
showed improvement in time to progression for patients on
Transplant Connection A National Marrow Donor Program/Be The Match publication
lenalidomide maintenance compared to placebo after
transplantation. [3,4] In addition, the CALGB/USA trial showed
overall survival advantage as well for patients taking maintenance
lenalidomide.
In a meta-analysis of 8 randomized trials, a benefit in both
progression-free and overall survival were noted in patients on
immunomodulatory drug-based maintenance strategy. [5] The
ASBMT Guidelines recommend lenalidomide-based maintenance
unless a contraindication exists. In high-risk disease with renal
failure or with adverse chromosome changes, consolidation and
maintenance with a bortezomib-based regimen may be considered.
1.
Shah N, Callander N, Ganguly S, et al. Hematopoietic stem cell transplantation for
multiple myeloma: Guidelines from the American Society for Blood and Marrow
Transplantation. Biol Blood Marrow Transplant. 2015; 21(7): 1155-1166.
2.
Attal M, Harousseau JL, Stoppa AM, et al. A prospective, randomized trial of
autologous bone marrow transplantation and chemotherapy in multiple myeloma.
Intergroupe Français du Myélome. N Engl J Med. 1996; 335(2): 91-97.
3.
Attal M, Lauwers-Cances V, Marit G, et al. Lenalidomide maintenance after stemcell transplantation for multiple myeloma. N Engl J Med. 2012; 366(19): 17821791.
4.
McCarthy PL, Owzar K, Hofmeister CC, et al. Lenalidomide after stem-cell
transplantation for multiple myeloma. N Engl J Med. 2012; 366(19): 1770-1781.
5.
Ye X, Huang J, Pan Q, Li W. Maintenance therapy with immunomodulatory drugs
after autologous stem cell transplantation in patients with multiple myeloma: a
meta-analysis of randomized controlled trials. PloS One. 2013;8:e72635.
Visit the Physicians Resource Center at: BeTheMatchClinical.org
Improved Survival in Multiple
Myeloma Over Time
Primary improvement in patients >65 years
A large-scale and long-term study of patients with multiple myeloma
has shown that overall survival has significantly improved since
2001. [1] The study analyzed the outcomes of 1,038 patients who
were started on therapy within 30 days of their diagnosis of
symptomatic multiple myeloma at the Mayo Clinic in Rochester,
Minn., between 2001 and 2010.
The researchers grouped patients into two time periods: between
2001 and 2005 (n=477) and between 2006 and 2010 (n=561).
Mean age at diagnosis was 66 years. The median follow up for the
entire patient cohort was 5.9 years.
Improved survival is benefitting older
patients and early mortality in this disease
has been reduced considerably.
Median overall survival (OS) for the entire cohort was 5.2 years.
The median overall survival of patients in the more recent group was
significantly longer compared with the earlier cohort: 6.1 years vs.
4.6 years, respectively (p=0.002). The estimated 6-year OS for the
recent cohort was significantly higher compared to the earlier
cohort: 51% vs. 40%, respectively (p<0.001).
Among the entire cohort, 393 patients (37%) received an
autologous hematopoietic cell transplant (auto-HCT) at some point
during the disease course, with a median time to transplant of 5.9
months (range, 2-95). A higher percentage of patients ≤65 years
received an auto-HCT (277 of 498, or 56%). Researchers performed
a 6-month landmark analysis to examine the impact of auto-HCT on
OS. The median OS for patients who underwent auto-HCT was not
reached, compared with 4.9 years (95% CI; 4.2, 5.3) for those not
receiving an auto-HCT (p<0.001).
The study authors also noted that the improvement in survival was
primarily seen among patients >65 years, with 6-year OS improving
from 31% to 56% (p<0.001). Additional results show improvements
in early post-transplant mortality over time, with only a 10%
incidence during the first year post-transplant in the 2006-2010
group, compared with 17% in the 2001-2005 cohort (p<0.01).
The authors concluded that the improved outcomes were linked
closely to FISH-based risk stratification, use of one or more new
agents in initial therapy, such as the IMiD and proteasome inhibitor
classes of drugs, and the use of bortezomib for patients with
high-risk translocations and 17p deletion.
1.
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REGISTER FOR OUR 2016 SYMPOSIUM
We invite you to attend our fourth annual Advances in the
Blood and Marrow Transplantation: 2016 Symposium.
Hear from nationally recognized and local experts as they
explore state-of-the art therapeutic insights, novel clinical
trials research, and new posttransplant care strategies.
New sessions for 2016 include a nursing track focused on
providing care to posttransplant patients.
View program details and register: tinyurl.com/BMT2016
Featured speaker: Carl June, MD, Abramson Family Cancer
Research Institute, Philadelphia
Invited national experts:
• David Avigan, MD, Beth Israel Deaconess Medical Center,
Boston
• Helen Heslop, MD, Center for Cell and Gene Therapy,
Houston
• Stephanie Lee, MD, Fred Hutchinson Cancer Research
Center, Seattle
Event details:
• Date: April 16, 2016
• Time: 8:45 a.m.-3:30 p.m.
• Location: Overland Park Convention Center, 6000 College
Blvd., Overland Park, KS 66211
• Cost: Free, Preregistration: required
Kumar SK, Dispenzieri A, Lacy MQ, et al. Continued improvement in survival in
multiple myeloma: changes in early mortality and outcomes in older patients.
Leukemia. 2014; 28(5): 1122-1128.
©2015 National Marrow Donor Program
NP20569; DEC 2015