Recognizing and treating early relapse of multiple myeloma (MM) is a challenge for healthcare professionals. This program is designed to improve clinicians’ ability to distinguish between relapse and progression of disease in MM. In addition, the program compares the efficacy and safety of carfilzomib- and pomalidomide-based regimens in the treatment of relapsed MM, applies current and emerging treatment approaches to MM patients in early relapse, and reviews common adverse events that occur when using combination regimens to treat early relapsed myeloma.
Multiple Myeloma At First Relapse: Is My Patient Refractory to Lenalidomide?
Multiple Myeloma At First Relapse: Is My Patient Refractory to Lenalidomide?
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Hi, my name is Noa Biran from Hackensack, New Jersey, and today we're going to discuss Multiple Myeloma at First Relapse: Is My Patient Refractory to Lenalidomide?
So we have to first define what is the difference between relapsed and refractory myeloma. And these patients represent a diverse group. Patients can relapse while being off of therapy. And these patients may have been discontinued from treatment for various reasons, including toxicity, not necessarily progression. Patients can relapse while on active therapy. And there are a subset of patients which perhaps represent the most high-risk and difficult-to-treat patients who are considered primary refractory, and these are patients who never achieve a response to their primary appropriate therapy. Relapse disease is disease that's been previously treated and then progresses. And refractory disease is progressive disease while on active therapy or within 60 days of last treatment.
Disease progression is defined by IMWG criteria, and it can be defined by clinical relapse which is really an end-organ symptom, hypercalcemia, anemia, a new bone lesion, symptoms related to hyperviscosity, or renal dysfunction that is attributed to the monoclonal gammopathy.
Or IMWG defines a biochemical relapse, which is a 25% or greater increase in paraprotein parameters, M spike, urine M spike, or in the case of free light chains, it's defined by more than 10 mg/dL difference between the involved and the uninvolved free light chain in the serum or urine. A relapse from CR doesn't necessarily need to be treated. It represents appearance of the serum or urine M spike, but does not yet meet the definition of progression of disease. These patients really just have to have more frequent monitoring. And a relapse from MRD negativity is similar in that a bone marrow which once showed MRD negativity now shows MRD positivity, represents reemergence of the disease, but at this point, does not represent a need for change in therapy.
IMWG definition of progression is defined similarly, in that progression of disease represents an increase of 25% from the lowest value and a serum M spike has to be at least 0.5 g/dL, or above. Refractory disease and primary refractory disease we defined prior.
So, how do we really define patients who are lenalidomide-refractory? Because many of our patients who are on lenalidomide maintenance are on sub-therapeutic dose. So there are three things we can possibly do in these situations, increase the lenalidomide dose, add weekly dex, or switch to an alternative regimen, either a new IMiD, or a totally different monoclonal antibody or proteasome inhibitor-based regimen. We know that to be fully considered lenalidomide-refractory, patients have to have progression or less than a partial response on a full dose of lenalidomide.
When we look at patients who receive treatment on clinical trials, it's very important to define those who are lenalidomide-refractory, and that's because they have significantly different response to various therapies compared to lenalidomide exposed patients. And that's because their disease is much more refractory and has acquired many more mutations.
In this study, you can see that when compared to bortezomib and dex, patients who were LEN-refractory have inferior outcomes compared to those who are lenalidomide exposed. And various treatment regimens were explored to evaluate response in these lenalidomide-refractory patients. And in sequential order, you can see that combination of dara/bortezomib/dex, carfilzomib/dara/dex, and cetuximab, carfilzomib/dex are excellent treatment options in patients who are lenalidomide-refractory.
So to summarize, we know that relapse myeloma is previously treated myeloma that's progressed after prior therapy and requires a change in treatment. The definition of progression of disease is a 25% increase in the tumor burden from the lowest documented value. And in the case of an M spike, it needs a 0.5 g/dL increase or above from the nadir. We know that in our lenalidomide-refractory patients response rate is significantly reduced and it is important to choose triplet-based combinations with a change in two agents.
Thank you for joining me today, and I hope you learned something about lenalidomide-refractory myeloma.
You have been listening to CME on ReachMD. This activity is jointly provided by Global Learning Collaborative (GLC) and TotalCME, LLC. and is part of our MinuteCE curriculum.
To receive your free CME credit, or to download this activity, go to ReachMD.com/CME. Thank you for listening.
This activity has been designed to meet the educational needs of the interprofessional team, including community and academic medical oncologists/hematologists, advanced practice professionals, oncology nurses, oncology pharmacists, as well as other clinicians involved in the management of patients with multiple myeloma (MM).
After participating in this educational activity, participants should be better able to:
- Distinguish between relapse and progression of disease in multiple myeloma
- Compare the efficacy and safety of carfilzomib- and pomalidomide-based regimens in the treatment of relapsed multiple myeloma
- Apply current and emerging treatment approaches to multiple myeloma patients in early relapse
- Recognize common adverse events seen with combination regimens used to treat early relapsed multiple myeloma
In support of improving patient care, this activity has been planned and implemented by Global Learning Collaborative (GLC) and Total CME, LLC. GLC is jointly accredited by the American Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC) to provide continuing education for the healthcare team.
This activity was planned by and for the healthcare team, and learners will receive 1.0 Interprofessional Continuing Education (IPCE) credit for learning and change.
In accordance with the ACCME Standards for Integrity and Independence, Global Learning Collaborative (GLC) requires that individuals in a position to control the content of an educational activity disclose all relevant financial relationships with any ineligible company. GLC mitigates all conflicts of interest to ensure independence, objectivity, balance, and scientific rigor in all educational programs.
The following faculty have disclosed:
Noa Biran, MD, faculty for this educational event, receives research support from Merck, Amgen, BMS, Karyopharm, and Janssen; receives consulting fees from Sanofi, Amgen, Takeda, Karyopharm, GSK, Janssen, Pfizer, and BMS; and spouse is an employee for Boehringer Ingelheim.
Joseph Mikhael, MD, MEd, FRCPC, faculty for this educational event, receives research support from BMS; and receives consulting fees from Amgen, BMS, Janssen, Sanofi, and Takeda.
The following planners/reviewers/managers have disclosed:
Robert Garris, PharmD, MPH, planner for this educational event, has no relevant financial relationships with ineligible companies.
William Mencia, MD, FACEHP, CHCP, reviewer for this educational event, has no relevant financial relationships with ineligible companies.
Total CME, LLC., planners, and managers have no relevant commercial relationships to disclose.
All the relevant financial relationships for these individuals have been mitigated.
The views and opinions expressed in this educational activity are those of the faculty and do not necessarily represent the views of GLC and Total CME, LLC. This presentation is not intended to define an exclusive course of patient management; the participant should use his/her clinical judgment, knowledge, experience, and diagnostic skills in applying or adopting for professional use any of the information provided herein. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient's conditions and possible contraindications or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities. Links to other sites may be provided as additional sources of information. Once you elect to link to a site outside of MedEd On The Go, you are subject to the terms and conditions of use, including copyright and licensing restrictions, of that site.
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This activity is supported by an independent educational grant from Bristol Myers Squibb.
Jointly provided by Global Learning Collaborative (GLC) and Total CME, LLC.
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