Customize
Quick Links
Specialties

Accreditation/Credit Designation

Physicians' Education Resource®, LLC, is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

Physicians' Education Resource®, LLC, designates this enduring material for a maximum of 1.5 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Acknowledgment of Commercial Support

This activity is supported by an educational grant from Sanofi Genzyme.

Medical Crossfire®: Personalizing Care for Multiple Myeloma Patients: Current and Future Sequencing Strategies

Release Date: May 31, 2018
Expiration Date: May 31, 2019
Media: Internet - based

 

Activity Overview

Treatment of multiple myeloma has changed dramatically in recent years with the emergence of novel agents and a variety of doublet, triplet, or even quadruplet combination regimens. In this rapidly evolving field, it can be difficult for practicing clinicians to stay abreast of the potential clinical implications of emerging data and novel treatments on the horizon. Through a lively, interactive discussion format, top experts in the field will provide their insights and perspectives on recent changes in the diagnosis and treatment of multiple myeloma, including patient and disease characteristics that influence treatment choice and sequencing strategies for existing and novel agent therapies. You will get an up-close look at how the faculty apply clinical study data in their everyday practice and learn about the panel's forward-looking perspectives on emerging data on novel multiple myeloma treatments on the horizon.

By participating in this exciting program, you will learn about:

  • Factors that influence treatment decisions for newly diagnosed and relapsed/refractory MM
  • Adjunctive measures to decrease the likelihood of adverse events associated with treatments
  • Emerging data on novel MM therapies in late-stage development
  • Considerations when referring a patient for a clinical trial

 

Acknowledgement of Commercial Support

This activity is supported by an educational grant from Sanofi Genzyme.

Requirements for Successful Completion

  • You will need to login to participate in the activity.
  • Each presentation may contain an interactive question(s). You may move forward through the presentation; however, you may not go back to change answers or review videos/content until you finish the presentation.
  • At the end of the activity, “educational content/video” will be available for your reference.
  • In order to receive a CME certificate, participants must complete the activity.
  • Complete the posttest and pass with a score of 70% or higher, complete the evaluation and then click on request for credit. Participants may immediately download a CME certificate upon completion of these steps.


Target Audience

This educational activity is directed toward medical oncologists, oncology pathologists, clinical/biomedical researchers, nurse practitioners, physician assistants, nurses, and other healthcare professionals interested in the treatment of multiple myeloma. This activity will provide education to a broad multidisciplinary team who are invited to participate.

Learning Objectives

At the conclusion of this activity, you should be better prepared to:

  • Examine current clinical trials supporting the optimal use of treatments in the context of initial therapy, treatment of relapsed multiple myeloma, and management of patients seeking autologous stem cell transplantation (ASCT)
  • Describe the role of novel agents in the induction, consolidation, and maintenance phases of patients eligible for ASCT
  • Identify treatments and recommend patients for participation in appropriate clinical trials of novel therapeutic modalities in development for multiple myeloma management


Faculty, Staff, and Planners' Disclosures

Moderator

C. Ola Landgren, MD, PhD
Professor of Medicine and Chief of Myeloma Service
Department of Medicine
Division of Hematologic Oncology
Memorial Sloan Kettering Cancer Center
New York, NY

Disclosure: No relevant financial relationships with commercial interests to disclose.

Faculty

Ajai Chari, MD
Associate Professor
Medicine, Hematology, and Medical Oncology
The Mount Sinai Hospital
New York, NY
 

Disclosure: Grant/Research Support: Takeda, Celgene, Novartis, Janssen; Consultant: Takeda, Celgene, Novartis, Janssen, Bristol-Myers Squibb

Pamela Crilley, DO
Medical Oncologist, Eastern Regional Medical Center
Chair, Medical Oncology/Medicine and Science
Cancer Treatment Centers of America®
Philadelphia, PA
 

Disclosure: No relevant financial relationships with commercial interests to disclose.

Giada Bianchi, MD
Instructor in Medicine, Harvard Medical School
Attending Physician, Jerome Lipper Multiple Myeloma Center
Dana-Farber Cancer Institute
Boston, MA
 

Disclosure: No relevant financial relationships with commercial interests to disclose.

The staff of Physicians' Education Resource®, LLC have no relevant financial relationships with commercial interests to disclose.

Disclosure Policy and Resolution of Conflicts of Interest (COI)

As a sponsor accredited by the ACCME, it is the policy of PER® to ensure fair balance, independence, objectivity, and scientific rigor in all of its CME activities. In compliance with ACCME guidelines, PER® requires everyone who is in a position to control the content of a CME activity to disclose all relevant financial relationships with commercial interests. The ACCME defines “relevant financial relationships” as financial relationships in any amount occurring within the past 12 months that creates a COI.

Additionally, PER® is required by ACCME to resolve all COI. PER® has identified and resolved all COI prior to the start of this activity by using a multistep process.

Off-Label Disclosure and Disclaimer

This CME activity may or may not discuss investigational, unapproved, or off-label use of drugs. Participants are advised to consult prescribing information for any products discussed. The information provided in this CME activity is for continuing education purposes only, and is not meant to substitute for the independent medical judgment of a physician or nurse relative to diagnostic, treatment, or management options for a specific patient's medical condition.

The opinions expressed in the content are solely those of the individual faculty members and do not reflect those of PER® or any of the companies that provided commercial support for this activity.

PER Pulse Recap™

PER Pulse Recap (1 of 3)

This first of 3 PER Pulse™ Recaps from the continuing medical education (CME) activity, Medical Crossfire®: Personalizing Care for Multiple Myeloma Patients: Current and Future Sequencing Strategies, focuses on treatment considerations for patients with newly diagnosed multiple myeloma (NDMM), including perspectives on optimal induction therapy and the use of autologous stem cell transplantation (ASCT).
 
In the United States, proteasome inhibitor/immunomodulatory drug triplet regimen—typically bortezomib (V) or carfilzomib (K) + lenalidomide (R)/dexamethasone (D) has become the standard of care for patients with NDMM, except in patients who cannot tolerate it. Elderly/frail patients may require a modified dosing regimen. While some experts reserve carfilzomib regimens for young, fit patients with high-risk disease, others prefer using carfilzomib for all patients regardless of risk status.

“In a disease where there is no curative therapy, why would I scale back if I really didn't have to due to toxicity or comorbidities. I have always thought of giving the best therapy to every patient, because the patient with the standard risk, they do the best with the best therapy, while the high-risk patients, they need the best therapy.”  
-- C. Ola Landgren, MD, PhD

In the real world, you don't have to be married to a particular regimen. There is an element of risk adaptation and response evaluation. If you start somebody on a bortezomib-triplet regimen and they either have intolerance due to neuropathy or if they have a suboptimal response, by all means you can switch to a carfilzomib regimen.”  
-- Ajai Chari, MD

Although ASCT is typically done early, some experts consider freezing the cells for a potential later transplantation and moving directly to a maintenance regimen in patients who have achieved minimal residual disease (MRD) negativity or, in some cases, delaying transplantation to accommodate patient preferences.
 
In clinical studies, MRD negativity is associated with significantly improved progression-free survival (PFS) and overall survival (OS).1,2 Regardless of whether you achieve that with a transplant or without a transplant, the major benefit comes with a deep remission. The use of MRD to monitor disease status will likely expand to mainstream clinical practice once MRD assays are standardized and become widely available.

References
  1. Landgren O, Devlin S, Boulad M, et al. Role of MRD status in relation to clinical outcomes in newly diagnosed multiple myeloma patients: a meta-analysis. Bone Marrow Transplant. 2016;51(12):1565-1568.
  2. Munshi NC, Avet-Loiseau H, Rawstron AC, et al. Minimal residual disease predicts superior survival in patients with multiple myeloma: a meta-analysis. JAMA Oncol. 2017;3(1):28-35.

PER Pulse Recap (2 of 3)

This second of 3 PER Pulse™ Recaps from the continuing medical education (CME) activity, Medical Crossfire®: Personalizing Care for Multiple Myeloma Patients: Current and Future Sequencing Strategies, focuses on current treatment strategies in patients with relapsed/refractory multiple myeloma (R/R MM), including novel agents and recent clinical trial data.
 
Despite numerous advances in the field of MM management, the treatment of R/R disease remains a significant challenge. Recent clinical studies have implications in the evolving landscape of the management of R/R MM, including:
  • ENDEAVOR1
  • Median overall survival (OS,) carfilzomib + dexamethasone (Kd; 47.5 months) vs bortezomib + dexamethasone (Vd; 40.0 months); P =.010
  • ASPIRE2
  • Median OS, carfilzomib + lenalidomide + dexamethasone (KRd; 48.3 months) vs Rd (40.4 months); P =.010
  • POLLUX3 - Rd +/-daratumumab
  • Median progression-free survival (PFS) not reached in daratumumab/Rd treatment arm vs 17.5 months (Rd); P <.0001
  • MRD-negative (10-5 sensitivity): daratumumab/Rd (26%) vs Rd (6%); P <.0001
  • CASTOR4 - Vd +/- daratumumab
  • Median PFS in patients with 1 prior line of therapy not reached with daratumumab/Vd vs 7.9 months (Vd); P <.0001
  • ELOQUENT-25 - Rd +/- elotuzumab
  • Elotuzumab/Rd reduced risk of progression/death by 27% vs Rd; P =.0014
  • OPTIMISMM6 - Vd +/- pomalidomide (P)
  • All patients lenalidomide-exposed; 70% lenalidomide-refractory
  • Median PFS 20.7 months with PVd vs 11.6 months with Vd; P =.0027
“We now have ASPIRE, ENDEAVOR, and ELOQUENT, all of them showing that PFS benefit translated to OS benefit. So I think that is an important message."  
-- Ajai Chari, MD

There is no one definitive treatment regimen for R/R MM, and management decisions often depend on the patient's prior therapy and risk status. Current strategies include:
  • Incorporation of an anti-CD38 monoclonal antibody (eg, daratumumab)
  • Use of an alternate immunomodulatory agent from first line (eg, pomalidomide)
  • Use of an alternate proteasome inhibitor (eg, carfilzomib if already received bortezomib)
“The data with both daratumumab + bortezomib/dexamethasone and daratumumab + lenalidomide/dexamethasone were highly positive with extraordinary results, but the population of high-risk patients that were included in these trials was somewhat a minority of the patients. Carfilzomib has been proven over and over again to rescue patients from immunomodulatory agent‒ and proteasome inhibitor‒resistant disease and patients with highly aggressive myeloma.”
-- Giada Bianchi MD

Several experts have successfully implemented a rapid infusion method (90 minutes)7 for daratumumab beginning at the third dose, which is well-received by their patients and clinical staff.
 
The importance of evidence-based clinical decision making cannot be overstated. Ongoing clinical trials will help to address many unanswered questions about treatment of patients with R/R MM.

References
  1. Dimopoulos MA, Goldschmidt H, Niesvizky R, et al. Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised phase 3 trial. Lancet Oncol. 2017;18:1327-1337.
  2. Siegel DS, Dimopoulos MA, Ludwig H, et al. Improvement in overall survival with carfilzomib, lenalidomide, and dexamethasone in patients with relapsed or refractory multiple myeloma. J Clin Oncol. 2018;36(8):728-734
  3. Dimopoulos MA, White DJ, Benboubker L, et al. Daratumumab, lenalidomide, and dexamethasone (DRd) versus lenalidomide and dexamethasone (Rd) in relapsed or refractory multiple myeloma: updated efficacy and safety analysis of POLLUX. Presented at the 59th American Society of Hematology Annual Meeting & Exposition; December 9-12, 2017; Atlanta, GA. Abstract 739.
  4. Spencer A, Hungria VTM, Mateos MV, et al. Daratumumab, bortezomib, and dexamthasone (DVd) versus bortezomib and dexamethasone (Vd) in relapsed or refractory multiple myeloma: updated efficacy and safety analysis of CASTOR. Presented at the 59th American Society of Hematology Annual Meeting & Exposition; December 9-12, 2017; Atlanta, GA. Abstract 3145.
  5. Dimopoulos MA, Lonial S, White D, et al. Elotuzumab plus lenalidomide/dexamethasone for relapsed or refractory multiple myeloma: ELOQUENT-2 follow-up and post hoc analyses on progression-free survival and tumor growth. Br J Haematol. 2017;178(6):896-905.
  6. Richardson PG, Rocafiguera AO, Beksac M, et al. Pomalidomide (POM), bortezomib, and low‐dose dexamethasone (PVd) vs bortezomib and low-dose dexamethasone (Vd) in lenalidomide (LEN)-exposed patients (pts) with relapsed or refractory multiple myeloma (RRMM): phase 3 OPTIMISMM trial. Presented at the 2018 American Society of Clinical Oncology Annual Meeting; June 1-5, 2018; Chicago, IL. Abstract 8001.
  7. Barr H, Dempsey J, Waller A, et al. Ninety-minute daratumumab infusion is safe in multiple myeloma. Presented at the 59th American Society of Hematology Annual Meeting & Exposition; December 9-12, 2017; Atlanta, GA. Abstract 1889.

PER Pulse Recap (3 of 3)

This third of 3 PER Pulse™ Recaps from the continuing medical education (CME) activity, Medical Crossfire®: Personalizing Care for Multiple Myeloma Patients: Current and Future Sequencing Strategies, focuses on factors to consider when referring a patient for a clinical trial and emerging data on promising multiple myeloma (MM) therapies in development, including second-generation anti-CD38 monoclonal antibodies (mAbs), antibody-drug conjugates (ADCs), CAR T cells, and novel small molecules.
 
Patients with highly relapsed/refractory multiple myeloma (R/R MM) have very little hope for remission with standard US Food and Drug Administration (FDA) regimens. In such cases, clinicians may consider referring the patient for a clinical trial. Some promising agents in development for the treatment of MM include
 
  • Anti-CD38 mAbs
  • Daratumumab subcutaneous (SC) (Janssen/J&J)
  • Phase 3: daratumumab SC vs daratumumab IV in R/R MM; recruiting1
  • Isatuximab (Sanofi Genzyme), FDA submission expected late 2018
  • Phase 3: pomalidomide/dexamethasone +/- isatuximab in R/R MM; active, not recruiting2
  • Phase 3: carfilzomib/dexamethasone +/- isatuximab in R/R MM; recruiting3
  • Phase 3: bortezomib/dexamethasone +/- isatuximab in newly diagnosed (NDMM); recruiting4
  • B-cell maturation antigen (BCMA)‒targeted CAR T-cell therapy
  • LCAR-B38M (Nanjing Legend Biotech)
  • Chinese Phase I study in patients with R/R MM – Early data presented at ASCO 2017 on 19 patients; ORR 100%5
  • US Phase I study to begin soon
  • bb2121 (Bluebird Bio
  • Early Phase I data presented at ASH 2017 on 21 patients with R/R MM (median 7 prior lines of therapy); ORR 89%6
  • ORR 100% in patients receiving ≥150 x 106 CAR T cells
  • CAR T- BCMA (Penn/Novartis)
  • Early Phase I data presented at ASH 2017 on 21 patients with R/R MM7
  • Anti-BCMA ADC
  • GSK2857916 (GlaxoSmithKline)
  • Early Phase I data from dose-escalation and -expansion study in R/R MM with PD <60 days of last treatment, presented at ASH 20178
  • 60% ORR in 35 heavily pretreated patients in dose-expansion phase
  • Novel small molecules
  • Venetoclax (AbbVie) - bcl-2 inhibitor (oral), FDA-approved for CLL
  • Early Phase I data of venetoclax + dexamethasone for patients with t(11;14), presented at ASH 20179
  • ORR 65% (13/20 patients) – 7 VGPR, 6 PR
  • Selinexor (Karyopharm) - XPO-1 inhibitor, oral; FDA submission expected
in late 2018
  • Phase IIb in combination with low-dose dexamethasone; ORR 20% in patients with penta-refractory R/R MM10
  • Phase III with bortezomib and low-dose dexamethasone is ongoing11
“We look forward to know how isatuximab is going to play out in combination with pomalidomide and dexamethasone. In preclinical studies, in cell lines and in vitro studies, it seems that it may have more direct cytotoxicity, more crosslinking of CD38, and more apoptosis compared to daratumumab. Of course, there is a limitation of preclinical studies. That's why we do the clinical studies.”  
-- Giada Bianchi, MD

Patients must be fit to undergo CAR T cell therapy, and patients with particularly aggressive disease are often not good candidates because they cannot be suitably managed during the 4 to 6 weeks of processing time to prepare the CAR T cells. Patients who have received any other anti‒BCMA-targeted therapy would not be candidates for current CAR T cell therapies in development because they all target BCMA. Cytokine release syndrome is a common adverse event with CAR T cell therapy.

“The proof of principle is there [for CAR T cell therapy]. It does work as a mechanism to go after multiple myeloma. I think it is fair to say there are quite limited number of patients who have been treated in the world at this point. And I think it is also fair to say there are not very many patients at this current time that have been followed beyond 1 year…We have seen relapses.”
-- C. Ola Landgren, MD, PhD

References
  1. A Study of Subcutaneous Versus (vs.) Intravenous Administration of Daratumumab in Participants With Relapsed or Refractory Multiple Myeloma. https://clinicaltrials.gov/ct2/show/NCT03277105. Accessed June 11, 2018.
  2. Multinational Clinical Study Comparing Isatuximab, Pomalidomide, and Dexamethasone to Pomalidomide and Dexamethasone in Refractory or Relapsed and Refractory Multiple Myeloma Patients (ICARIA-MM). https://clinicaltrials.gov/ct2/show/NCT02990338. Accessed June 11, 2018.
  3. Multinational Clinical Study Comparing Isatuximab, Carfilzomib and Dexamethasone to Carfilzomib and Dexamethasone in Relapse and/or Refractory Multiple Myeloma Patients (IKEMA). https://clinicaltrials.gov/ct2/show/NCT03275285. Accessed June 11, 2018.
  4. Clinical Benefit of SAR650984, Bortezomib, Lenalidomide and Dexamethasone Combination in NDMM Patients Not Eligible for Transplant (IMROZ). https://clinicaltrials.gov/ct2/show/NCT03319667. Accessed June 11, 2018.
  5. Fen F, Zhao W, Liu J, et al. Durable remissions with BCMA-specific chimeric antigen receptor (CAR)-modified T cells in patients with refractory/relapsed multiple myeloma. Presented at the 2017 American Society of Clinical Oncology Annual Meeting; June 2-6, 2017; Chicago, IL. Abstract LBA3001.
  6. Berdeja JG, Lin Y, Raje N, et al. Durable clinical responses in heavily pretreated patients with relapsed/refractory multiple myeloma: updated results from a multicenter study of bb2121 anti-BCMA CAR T cell therapy. Presented at the 59th American Society of Hematology Annual Meeting & Exposition; December 9-12, 2017; Atlanta, GA. Abstract 740.
  7. Cohen AD, Garfall AL, Stadtmauer EA, et al. Safety and efficacy of B-cell maturation antigen (BCMA)-specific chimeric antigen receptor T cells (CART-BCMA) with cyclophosphamide conditioning for refractory multiple myeloma. Presented at the 59th American Society of Hematology Annual Meeting & Exposition; December 9-12, 2017; Atlanta, GA. Abstract 505.
  8. Trudel S, Lendvai N, Popat R, et al. Deep and durable responses in patients with relapsed/refractory multiple myeloma treated with monotherapy GSK2857916, an antibody drug conjugate against B-cell maturation antigen (BCMA): preliminary results from part 2 of study BMA117159. Presented at the 59th American Society of Hematology Annual Meeting & Exposition; December 9-12, 2017; Atlanta, GA. Abstract 741.
  9. Kaufman JL, Gasparetto CJ, Mikhael J, et al. Phase I study of venetoclax in combination with dexamethasone as targeted therapy for t(11;14) relapsed/refractory multiple myeloma. Presented at the 59th American Society of Hematology Annual Meeting & Exposition; December 9-12, 2017; Atlanta, GA. Abstract 3131.
  10. Vogl DT, DIngli D, Cornell RF, et al. Selective inhibition of nuclear export with oral selinexor for treatment of relapsed or refractory multiple myeloma. J Clin Oncol. 2018;36(9):859-866.
  11. Delimpasi S, Pour L, Auner HW, et al. A phase 3 randomized, controlled, open-label study of selinexor, bortezomib, and dexamethasone (SVd) versus bortezomib and dexamethasone (Vd) in patients with relapsed or refractory multiple myeloma (RRMM). Presented at the 2018 American Society of Clinical Oncology Annual Meeting; June 1-5, 2018; Chicago, IL. Abstract TPS8056.







Become a Member

Forgot Password?
Calendar of Events
SUNMONTUESWEDTHURSFRISAT
     12
3456789
10111213141516
17181920212223
24252627282930
Filter By