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.
Pomalidomide-Based Regimens in Early Relapse Multiple Myeloma
Pomalidomide-Based Regimens in Early Relapse Multiple Myeloma
Welcome to CME on ReachMD. This episode is part of our MinuteCE curriculum.
Prior to beginning the activity, please be sure to review the faculty and commercial support disclosure statements as well as the learning objectives.
Hello, my name is Dr. Joseph Mikhael, and I'm going to be talking today about Pomalidomide-Based Regimens in Early Relapse Multiple Myeloma.
And when we think about early relapse in myeloma, we can divide patients into those who are LEN-refractory, and those who are LEN-sensitive. We can see here that the studies I'm going to highlight are primarily in lenalidomide-refractory patients.
Starting with the OPTIMISMM study, which is randomized study of adding pomalidomide with bortezomib and dexamethasone, versus bortezomib and dexamethasone alone. And this was an important study, because we definitely saw a significant improvement in progression-free survival in those patients that had the pomalidomide added to the bortezomib and dexamethasone, with a hazard ratio of 0.61. And so this is a commonly used regimen, even internationally.
The one that we see perhaps the greatest use in North America would be the APOLLO study, which took pomalidomide and dexamethasone, and now added daratumumab to it, versus pomalidomide and dexamethasone alone. And so in the APOLLO study in which patients were mostly had had at least one - all had had at least one prior line, although the majority had had two prior lines of therapy, we saw again that the triplet was superior to the doublet in progression-free survival by adding about 5 months to it with pomalidomide/dex being at 6.9 months, and the dara/pon/dex being a little over a year at 12.4 months. This was then followed up with the follow-up data at ASH in 2021 with a very similar outcome, where again, we saw this roughly 5-month benefit of adding the daratumumab to the pomalidomide and dexamethasone.
We also have a smaller MM014 study using daratumumab/pomalidomide/dex in the non-randomized fashion here in Cohort B, as you see, where these patients who had fewer lines, the majority were one or two prior lines. And in that situation, we saw a median PFS of actually up to 31 months. So we know that we can use pomalidomide in LEN-refractory patients, even in those who again were most recently LEN-refractory.
One of the largest phase 3 studies was adding a different CD38 antibody with isatuximab in the form of the ICARIA trial. So the ICARIA trial was a large phase 3 trial comparing isatuximab/pomalidomide/dex, versus pomalidomide/dex. Now, these patients had all had two prior lines of therapy, so they're a little bit further along than what we had just looked at. But again, we see this roughly 5- to 6-month benefit here of 6.5 months with pomalidomide and dexamethasone, to 11.5 months to the isatuximab plus pomalidomide and dexamethasone. And so we again see this recurring theme that we can use pomalidomide. And when we add a CD38 antibody to it, we see a benefit. Interestingly, in the ICARIA study, we actually now also see an overall survival analysis that was recently presented that demonstrates a benefit there from 17 months with pom/dex to about 24.5 months with isatuximab, pomalidomide, and dexamethasone.
And then, as we move to the ELOQUENT study, which is now adding elotuzumab to pomalidomide and dex, which we use more in this context because we're using elotuzumab less with lenalidomide by virtue of how many patients are LEN-refractory, we also saw in this ELOQUENT-3 study, a benefit of adding the elotuzumab to the pom/dex, as opposed to pom/dex alone, as you can see here, with a hazard ratio of 0.54, and this actually also had an overall survival analysis that demonstrated the benefit of Epd, or elotuzumab/pom/dex, over pom/dex alone.
So trying to put this all together and we know in relapse disease, that ongoing therapy is better for patients. We know that we can use triplets to overcome what we would be able to achieve only with doublets, and we still can divide patients basically into those who are lenalidomide-refractory and those who are not lenalidomide-refractory.
In those LEN-sensitive patients that I didn't discuss today, we have several options like DRd, KRd, and even IRd as we use the LEN-sensitive - use lenalidomide in those patients. Or now we can see in LEN-refractory patients, we have options like PVd, DVd, DPd, as well as the isatuximab/pom/dex, daratumumab/carfilzomib/dex, and isatuximab/carfilzomib/dex, which we will discuss in another episode. And just as a last comment, as we manage these patients with pomalidomide, we know it has a very similar side effect profile to lenalidomide and we manage them in a similar way.
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.
Reproduction of this material is not permitted without written permission from the copyright owner.
This activity is supported by an independent educational grant from Bristol Myers Squibb.
Jointly provided by Global Learning Collaborative (GLC) and Total CME, LLC.
During the period 8/25/2023 through 8/25/2024, registered participants wishing to receive continuing education credit for this activity must follow these steps:
1. Read the learning objectives and faculty disclosures.
2. Answer a pre-program question.
3. View the program.
4. Complete the post-test with a score of 100%.
5. Complete activity evaluation.
6. Apply for credit and either bank your credits or print your certificate.
For Pharmacists: Upon successfully completing the post-test with a score of 100% and the activity evaluation form, transcript information will be sent to the NABP CPE Monitor Service. This may require you to add or update the e-profile ID/date of birth information saved in your account.
Our site requires a computer, tablet, or mobile device and a connection to the Internet. For best results, a high-speed Internet connection is recommended (DSL/Cable/Fibre). We also recommend using the latest version of your favorite browser to ensure compliance with W3C standards, such as Chrome, Safari, Firefox, or Microsoft Edge.